Clinical efficacyof Aconitum-Containing Traditional Chinese medicinefor Diabetic Peripheral neuropathicpain

Diabetic peripheral neuropathyis a common chroniccomplication of diabetes. Routine clinical management usesanalgesicsto relievepainin combination with drugs for nerverepair. The drugs are often not effectivefor the severepaincases, and these western medicationsalso have side effects. We report a more effectivetreatmentof diabetic peripheral neuropathicpainusing a high dose of a traditional Chinese medicine, aconitum (including both Radix aconite preparata and Radix aconite kusnezoffii), in combination with Huangqi Guizhi Wuwu Tang (i.e., astragalus, cassia twig, white peony root, and spatholobi). In order to achieve strongeranalgesiceffects, we increased the clinical dosage of aconitum from 15 to 120 g. The aconitum was boiled for 6–8 hours, and licorice was also used to reducepotentialtoxicities of aconitum. In the four reportedcases, the patients’ neuropathicpainwas remarkably reducedand the EMG profile was also improvedwith this treatmentregimen. Adverse reactionswere not observedduring the therapy.

Thus, aconitum represents a promisingand safe treatmentfor the well-being of patients and their diabetic peripheral neuropathicpain. Future controlled clinical trials using traditional Chinese medicinescontaining aconitum in treatingthe neuropathicpainare warranted.

Attenuating effectof Acorus calamus extractin chronicconstriction injuryinducedneuropathicpainin rats: an evidenceof anti-oxidative, anti-inflammatory, neuroprotectiveand calcium inhibitoryeffects

Background : Acorus calamus (family: Araceae), is an indigenous plant, traditionally it is used as an ingredientof various cocktail preparations and for the management of severeinflammatorydisordersin Indian systemof medicine. Present study investigated the attenuating role of Acorus calamus plantextractin chronicconstriction injury(CCI) of sciaticnerveinducedperipheral neuropathyin rats.
Methods:Hot plate, plantar, Randall Selitto, Von Frey Hair, pin prick, acetone drop, photoactometer and rota-rod testswere performed to assess degree of thermal, radiant, mechanical, chemical sensation, spontaneous motor activityand motor co-ordination changes respectively, at different time intervals i.e., day 0, 1, 3, 6, 9, 12, 15, 18 and 21. Tissue myeloperoxidase, superoxide anion and total calcium levels were determined after 21^st day to assess biochemical alterations. Histopathological evaluations were also performed. Hydroalcoholic extractof Acorus calamus (HAE-AC, 100 and 200 mg/kg, p.o.) and pregabalin (10 mg/kg, p.o.) were administered from the day of surgery for 14 days.

Results : CCI of sciaticnervesignificantlyinducedthermal, radiant, mechanical hyperalgesiaand thermal, chemical, tactile allodynia, along with increasein the levels of superoxide anion, total calcium and myeloperoxidase activity. Moreover significanthistological changes were also observed. HAE-AC attenuatedCCI induceddevelopment of painful behavioural, biochemical and histological changes in a dose dependent manner similar to that of pregabalin serving as positive control.

Conclusion : Acorus calamus preventedCCI inducedneuropathywhich may be attributed to its multiple actionsincluding anti-oxidative, anti-inflammatory, neuroprotectiveand calcium inhibitoryactions.

Evaluation of anti-inflammatoryactivityand analgesiceffectof Aloe vera leafextractin rats

Clinical evaluation of analgesicand anti-inflammatorydrugs envisages the development of side effectsthat makes efficacyof a drug arguable. Alternatively, indigenous drug with fewer side effectsis the majorthrust area of research in the management of painand inflammation. In the present study aqueous extractof whole leafof Aloe vera at various concentrations was investigated for its anti-inflammatoryand analgesicactivitiesin albino wistar rats. Carrageenan and formaldehyde-inducedrat paw oedemawas used to evaluate the anti-inflammatoryactivityand tail flick, hot plate and acetic acid testswere used to assess the analgesicactivityof A. vera leafaqueous extracts.

Whole leafaqueous extractsat various concentrations (100, 200, 400, and 600 mg/kg of bw) significantlyreducedformation of oedemainducedby carrageenan and formaldehyde and granuloma formation in a dose dependent manner. Further, acetic acid-inducedwrithingmodel exhibitedsignificantanalgesiceffectcharacterized by reductionin writhes. Whole leafaqueous extractshoweddose-dependent increasein tolerance to thermal stimulus comparable to indomethacin. No mortality was observedduring the acutetoxicity test at a dosage of 600mg/kg. Thus whole leafaqueous extractof Aloe vera can be exploited as non toxic drug for the treatmentand clinical management of inflammationand pain.

effectof Alpinia officinarum Hance alcohol extractson primary dysmenorrheal

Objective : To study the effectof Alpinia officinarum Hance (A. officinarum) 80% alcohol extracton the primary dysmenorrhea.

Methods : A. officinarum 80% alcohol extractwere enriched by macroporous adsorption resins. Female mice of primary dysmenorrheamodel were established by oxytocin induction; the effectsof A. officinarum 80% alcohol extracton primary dysmenorrheawere observedby body twist method; and the homogenate level of prostaglandin F2a (PGF2a), prostaglandin E2 (PGE2) and Ca2+ in the uterus were observedin oxytocin-inducedfemale mice.

Results : The writhingfrequency of primary dysmenorrheamice was significantlydecreasedafter treatmentof A. officinarum 80% alcohol extractand the level of PGF2a, PGE2 and Ca2+ in mice uterus was significantlydecreased(P < 0.05, P < 0.01) in groups of mice treatedwith middle and high dosage of A. officinarum 80% alcohol extractcompared with that of model group.

Conclusion : These findingssuggest that A. Officinarum 80% alcohol extractcan significantlyrelieveprimary dysmenorrhea.

analgesicpropertiesof a hydroalcoholic extractobtained from Alternanthera brasiliana

The present study describes the analgesiceffectsof the hydroalcoholic extract(HE) obtained from the aerialpartsof Alternanthera brasiliana in two models of painin mice. Such an extract, given intraperitoneally or orallyproducedsignificantand long-lasting (0.5–4 h) antinociceptionwhen evaluated againstacetic acid-inducedabdominal constrictions. In the formalin test, the HE inhibitedboth the first and second phases of formalin-inducedpain.

Furthermore, the HE was more potentthan some standard drugs, such as aspirin, indomethacin and dipyrone, when evaluated againstacetic acid-inducedabdominal constrictions. These resultssuggest a strong analgesiceffectfor HE, possibly related to the presence of sterols, terpenes and phenoliccompounds, confirming the popular use of A. brasiliana againstdolorous processes.

analgesicand anti-inflammatorypropertiesof the leafextractsof Anacardium occidentalis in the laboratory rodents

Anacardium occidentalis (family: Anacardiaceae) is a plantof the tropical climate widely used by folklore to treatpainand inflammation. This study was conducted to evaluate the analgesicand anti-inflammatoryeffectsof the leafextractsin rat and mice using different models in other to confirmfolkloric claims. The aqueous, hexane, dichloromethane and methanol extracts(AEAO, HEAO, DEAO and MEAO respectively) were investigated for analgesiceffectsin acetic acid inducedpainin mice. They significantlyreducedthe number of writhing(p<0.001) and the highest analgesiceffectwas seen in DEAO extract. DEAO was further studied on various analgesicand anti-inflammatorymodels in graded doses. The extractsignificantlyreducedwrithinginducedby acetic acid and the number and time of paw licking inducedby formalin in a dose related manner. It inhibitedthe neurogenicand inflammatoryphases of formalin. analgesiawas shown in the inhibitionof nociceptioninducedby tail immersion in 55oC hot water. The extractprolonged the latencies of tail withdrawalto a similar degree as pentazocine.

The extractcausedsignificantinhibitionof carrageenan inducedpaw oedemain rats in a dose dependent manner. These findingssuggest that the leafextractsof Anacardium occidentalis are highly potentanalgesicand anti-inflammatoryagents. phytochemicalanalysis showedthat the leafextractscontain alkaloids, tannins, saponins and cardenolides.

antioxidant,antioedemaandanalgesicactivitiesof Andrographis paniculataextractsand theiractiveconstituent andrographolide

Andrographis paniculata (AP), a popularingredientof Orientalfolkmedicine, is commonly used fortreatinginfection,inflammation, fever and diarrhoea. In this study,extractsprepared from cultivated AP and theiractiveconstituent andrographolide were evaluated forantioxidant,antioedemaandanalgesicactivities. Theresultsshowedthat the aqueous APextract(AP-H₂O)exhibiteda greaterantioxidantactivitythan the ethanol APextract(AP-EtOH) in all modelsystems tested. At a concentration of 50 µg/mL, thefreeradicalscavenging, xanthine oxidaseinhibitionand antilipid peroxidationactivitiesfor AP-H₂O were 66.8%, 57.3% and 65.3%,respectively, and for AP-EtOH were 57.8%, 52.6% and 34.2%,respectively. At a dosage of 100 mg/kg, AP-H₂O and andrographolide, but not AP-EtOH,showedantioedemaandanalgesicactivities.

Inphytochemicalanalysis, AP-H₂Oshoweda higher concentration of totalflavanoidbut a lowerphenolcontent than AP-EtOH. Inconclusion, AP-H₂O was morepotentthan AP-EtOH inantioxidantactivities. Furthermore, compared with andrographolide, AP-H₂O as anextractalso appears topossesspotentantioedemaandanalgesicactivities.

analgesicandanti-inflammatoryactivityofAndrographis paniculataandAndrographolide in Diabetic Rodents

An analytically characterizedextractofAndrographis paniculataleaves(AP) and isolated pure andrographolide were evaluated fortheiranalgesicandanti-inflammatoryactivityin diabetic rodents. AP (100, 200 and 400 mg/kg/day,p.o.), or andrographolide (30, 60and 120 mg/kg/day,p.o.) was administered for ten consecutive days. Pentazocine and indomethacin were used as standardanalgesic andanti-inflammatorydrugs, respectively. Diabetic control animals weredemonstratedsignificantabnormalpain-associated behav-iours, measured ashyperalgesiatopainful stimuli in tail flick test, hot plate test and formalin-evokedpaintest, and exaggerated in-flammatoryresponses in carragennan-inducedpawoedemaand cotton pelletinducedgranulomatestsin comparison to nondiabeticcontrol animals. AP and andrographolidetreatments in diabetic animalsdemonstratedsignificantanalgesicandanti-inflammatory activityin all thesetests, and their maximal efficacies were always comparable to the standard drugs used.

Taken together, theseobservationsconfirmthat andrographolide is themajoractiveconstituent ofAndrographis paniculata,andstronglysuggest that anti-inflammatoryandanalgesicefficacies of AP are entirely due to the presence of high contents of andrographolide present in it.

Andrographis paniculataextractrelievespainandinflammationin Monosodium Iodoacetate-inducedosteoarthritisand Acetic Acid-inducedwrithingin Animal Models

Osteoarthritis(OA), being themostprominentdegenerativejointdisease is affecting millions ofelderlypeople worldwide. Although Andrographis paniculata is an ethnicmedicinewith a long history of being used asanalgesicagent, no study using a monosodium iodoacetate (MIA) model has investigated itspotentialactivitiesagainstOA. In this study, experimental OA wasinducedin rats with a knee injection of MIA, which represents the pathological characteristics of OA in humans. A. paniculataextract(APE)substantiallyreversedthe loss of hind limb weight-bearing and the cartilage damageresulted from the OA induction in rats.

Additionally, the levels of serumpro-inflammatorycytokines, such as IL-1ß, IL-6, and TNF-a as well as the concentration of matrix metalloproteinases, including MMP-1, MMP-3, MMP-8, and MMP-13 weredecreasedby APE administration. Acetic acid-inducedwrithingresponses in mice which quantitatively measurepainweresignificantlyreducedby APE. In vitro, APEinhibitedthe generation of NO and downregulated theexpressionof IL-1ß, IL-6, COX-2, and iNOS in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The aboveresultssuggest thepotentialuse APE as atherapeuticagentagainstOA.

A BRIEF OVERVIEW ON Andrographis paniculata (Burm. f) Nees., A HIGHvaluedmedicinalplant: BOON OVER SYNTHETIC DRUGS

Since time immemorial themedicinalplants, as sources ofremedies, are widely used as alternativetherapeutictool for thetreatmentof plethora ofacuteandchronicaldiseasesranging from common cold to complex humandiseasesall over the world. Following the advent of modernmedicine,herbalmedicinesuffered a set back, but due to the multiple drug resistance, sideeffectsassociated with antibiotics, restriction in use of syntheticantioxidantdrugs because of its carcinogenicity and limited availability of anticancer drugs has forced the scientist to search for new alternative substances fromplantorigin. A. paniculata is in demand in terms of its highvaluedmedicinalproperties. Extensive research on thisplantconsidered it as a good source ofmedicinalherbover the commercially available synthetic drugs.

It can be used for pharmaceutical applications, food preservation and also as a food supplement, in order to promote growth of live stock and toincreasethenutritionalvalueof different foods and diet.

analgesicand anti-inflammatoryeffectof the aqueous extractof Angelica dahurica

Background:Angelica dahurica has been used in various clinical cases. Its taste is hot and its property is warm, dry and nonpoisonous. Its efficacyis to remove wind-damp, cure swellingand edema, exhaust pus, stop itching, rhinitis and leukorrhea.

Object:To test through experiment Angelica dahurica’s analgesicand anti-inflammatoryefficacy.

Method:Inject acetic acid as a pain-inducingsubstance to the mice and measure visceral painbywrithingreflex. Inject carrageenan that is an edema-inducingsubstance to the rat’s paw and measure volume of edema. Take thermal painto mice with plantar test and measure paw withdrawallatency. Normal group is non Angelica dahurica-treatedgroup and treatedgroup is Angelica dahurica-treatedgroup.

Results:In acetic acid-inducedvisceral model, treatmentwith Angelica dahurica suppressedwrithingreflex significantlyand dose-dependently. In carrageenan-inducedpaw edemamodel, treatmentwith Angelica dahurica suppressedcarrageenan-inducedpaw edema. In plantar test model, no significanteffecton the withdrawallatency of thermal stimulation-inducednociceptionwas observed.

Conclusion:Angelica dahurica has analgesicand anti-inflammatoryefficacy.

anti-inflammatoryand analgesicactivitiesfrom rootsof Angelica pubescens

In the present study, we extracted Angelica pubescens (AP) with various solvents in order to find the bioactiveconstituents that demonstratedanalgesicand anti-inflammatoryeffects. The resultswere obtained as follows: (1) Methanol-, chloroform-, and ethyl acetate-extractseffectivelyreducedthe painthat was inducedby 1% acetic acid and a hot plate. (2) Methanol-, chloroform-, and ethyl acetate-extractsreducedthe edemathat was inducedby 3% formalin or 1.5% carrageenan. (3) Sixteen compounds have been isolated and identified from the rootsof AP. Among these compounds, columbianadin, columbianetin acetate, bergapten, umbelliferone, and caffeic acid significantlydemonstratedanti-inflammatoryand analgesicactivitiesat 10 mg/kg. However, only osthole and xanthotoxin revealedanti-inflammatoryactivity. Isoimperatorin only demonstratedan analgesiceffect.

analgesiceffectsand the mechanismsof anti-inflammationof Ergostatrien-3ß-ol from Antrodia camphorata Submerged Whole Broth in Mice

Ergostatrien-3ß-ol (ST1), an activeand majoringredientfrom Antrodia camphorata (AC) submerged whole broth was evaluated for the analgesicand anti-inflammatoryeffects. treatmentof male imprinting control region (ICR) mice with ST1 (1, 5, and 10 mg/kg) significantlyinhibitedthe numbers of acetic-acid-inducedwrithingresponse in 10 min. Also, our resultshowedthat ST1 (10 mg/kg) significantlyinhibitedthe formalin-inducedpainin the late phase (p < 0.001). In the anti-inflammatorytest, ST1 (10 mg/kg) decreasedthe paw edemaat 4 and 5 h after ?-carrageenin (Carr) administration and increased the activitiesof catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the liver tissue.

We also demonstratedthat ST1 significantlyattenuatedthe malondialdehyde (MDA) level in the edemapaw at 5 h after Carr injection. ST1 (1, 5, and 10 mg/kg) decreasedthe nitric oxide (NO) levels on both the edemapaw and serum level at 5 h after Carr injection. Also, ST1 (5 and 10 mg/kg) diminished the serum tumor necrosis factor (TNF-a) at 5 h after Carr injection. Western blotting revealedthat ST1 (10 mg/kg) decreasedCarr-inducedinducible nitric oxide synthase (iNOS), and cycloxyclase (COX-2) expressions at 5 h in the edemapaw. An intraperitoneal (ip) injection treatmentwith ST1 also diminished neutrophil infiltration into sites of inflammation, as did indomethacin (Indo). The anti-inflammatorymechanismsof ST1 might be related to the decreasein the level of MDA, iNOS, and COX-2 in the edemapaw via increasingthe activitiesof CAT, SOD, and GPx in the liver through the suppression of TNF-a and NO.

antinociceptiveand anti-inflammatoryactivitiesof Aquilaria sinensis (Lour.) Gilg. leavesextract

Aim of the study: The analgesicand anti-inflammatoryactivitiesof the ethanol extractof Aquilaria sinensis (Lour.) Gilg. leaveswere observedin various experimental models related to nociceptionand inflammation, so as to providesome evidencefor its traditional use.

Materials and methods: Acetic acid-inducedwrithingand a hot plate test in mice were used to evaluate its analgesicactivity. On the other hand, its anti-inflammatoryactivitywas observedin xylene or carrageenan-inducededema, carboxymethylcellulose sodium (CMC-Na)-inducedleukocyte migration in mice and lipopolysaccharide (LPS)-inducednitric oxide (NO) release from mouse peritoneal macrophages in vitro.

Results:The ethanol extractsignificantlyinhibitedacetic acid-inducedwrithingafter single oraladministration at doses of 424 and 848 mg extract/kg, and the response to the thermal stimulus in mice at the dose of 848 mg/kg. Meanwhile, the ethanol extractalso remarkably lessened xylene-inducedear swelling, carrageenan-inducedpaw edema, and CMC-Na-inducedleukocyte migration. Furthermore, the extractconsiderably reducedNO release from LPS-stimulated macrophages with IC50 of 80.4 mg/ml.

Conclusion:These findingssuggest that Aquilaria sinensis (Lour.) Gilg. leavesextractpresent notable analgesicand anti-inflammatoryactivities, which support its folkloric use for some diseasesrelated with painful and inflammatoryconditions such as traumaetc.

Ardisia: health-promotingpropertiesand toxicity of phytochemicals and extracts

Ardisia species (Myrsinaceae) are foundthroughout tropical and subtropical regions of the world. Traditional medicinalusesattributed to Ardisia include alleviationof liver cancer, swelling, rheumatism, earache, cough, fever, diarrhea, broken bones, dysmenorrhea, respiratory tract infections, traumaticinjuries, inflammation, pain, snake and insect bites, birth complications and to improvegeneral blood circulation, among others. Ardisia species are rich in polyphenols, triterpenoid saponins, isocoumarins, quinones and alkylphenols. A summary of the uses, potentialhealthbenefits, adverse reactionsand importantbioactivephytochemicals isolated from the Ardisia species is presented.

Future research needs to include more toxicological studies, more comprehensive chemical characterization of extracts, bioavailability, extractstandardization, investigation of possible herb–drug interactions, plantimprovementwith regards to bioactivityand composition, and additional human and animal studiesto confirmthe health-promotingpropertiesclaimed for Ardisia species. The information presented here exemplifies the potentialof Ardisia species as a source of chemotherapeutic, chemo-modulating and/or chemopreventiveagents.

anti-inflammatoryand analgesicactivitiesof Artemisia absinthium and Chemical Composition of its essentialOil

Nature has been a source of medicinalagentsfor thousands of years and has been isolated the number of modern drugs from naturalresources. Artemisia absinthium used for a variety of medicinalpurposes and therapeutictargets in all over the world, such as localized pains, contusion inflammation, anti-rheumatic, include fever reduction, digestive ailments and muscle pain. This study aimed to assess the anti-inflammatoryand anti-nociceptiveactivityof essentialoil and aqueous extractfrom Artemisia absinthium for the first time.

Chemical compositions of the essentialoil were determined by GC/MS. The anti-inflammatoryactivitywas evaluated by carrageenan-inducedpaw edemain mice. analgesicactivitywas assessed by acetic acid-inducedwrithing, formalin and hot plate testsin mice. Pretreatment with the essentialoil (at the dose of 2, 4 and 8mg/kg) and aqueous extract(50, 100 and 200mg/kg) showedpotentialanti-inflammatoryand anti-nociceptiveeffectsto different level. The essentialoil at 4 and 8 mg/kg significantlyreducedcarrageenan inducedpaw edema. The essentialoil and aqueous extractproducedsignificantdecreasednumber of writhingin acetic acid-inducedwrithingmodel and increased the response latency in hot plate test after 30 min.

Both essentialoil and aqueous extractsignificantlysuppressedin a dose-dependent manner the nociceptiveresponse in the formalin test, while the effecton the late phase was more pronounced. GC–MS analyses showedthe presence of twenty componentsin essentialoil. The essentialoil and aqueous extractpossessesexcellent anti-inflammatoryactivityas well as antinociceptivepropertiesespecially peripheral analgesic.

STUDY OF analgesicAND ANTI inflammatoryactivityFROM plantextractsOF LACTUCA SCARIOLA AND ARTEMISIA ABSINTHIUM

Seeds and samples of stems from the two medicinalplants, Lactuca scariola and Artemisia absinthium respectivelywere extracted in absolute methanol to determine their analgesicand anti-inflammatory activity. The analgesicactivitywas assessed on intact mice by tail flick latency in tail immersion method. The anti-inflammatoryactivitywas estimated volumetrically by measuring the mean increasein hind paw volume of rat with the help of plethysmometer. Acetylsalicylic acid in the dose of 300 mg/kg is used as standard drug. Both plantextractswere given in the doses of 300, 500 and 1000 mg/kg. Control group received 0.9% NaCI (saline) solution. All the doses administered orally. resultsshowedthat Lactuca had potentanalgesicactivityand Artemisia had significantanalgesicand anti-inflammatoryactivity.

Study on analgesiceffectsof aqueous extractfrom Asari Radix et Rhizoma combined with Nimodipine and its mechanism

Objective:To study the analgesiceffectsof aqueous extractfrom Asari Radix et Rhizoma (ARR) combined with Nimodipine and its mechanism.

Methods:Forty healthy male Wistar rats were r andomly divided into control, model, ARR, Nimodipine, and ARR+Nimodipine groups. Except the control group, the neuropathicpainmodels of rats were producedin the rest groups by the ligation of sciaticnerve. Rats in each group were ig administered for two weeks after operation. The aqueous extract(200 mg/kg) from ARR was given to rats in ARR group, Nimodipine (40 mg/kg) was given to rats in Nimodipine group, and the aqueous extract(200 mg/kg) from ARR was given to rats after 30 min administration of Nimodipine (40 mg/kg) in ARR+Nimodipine group, and physiological saline was given to rats in the control and model groups. Thermal paw withdrawallatency and mechanical paw withdrawalreflex threshold of rats in each group were measured on one day before operation and on the days 1, 3, 5, 9, and 14 after 30 min of administration.

Results:The thermal paw withdrawallatency and mechanical paw withdrawalreflex threshold of rats in each group were not significantlydifferent before and after the operation (P>0.05). The thermal paw withdrawallatency and mechanical paw withdrawalreflex threshold of rats in the model group were significantlylower than those in the control group at various time points after the operation (P<0.05 and 0.01). The thermal paw withdrawallatency and mechanical paw withdrawalreflex threshold of rats in ARR and Nimodipine groups were significantlyhigher than those in the model group from the day 5 after the operation (P<0.05 and 0.01). The thermal paw withdrawallatency and mechanical paw withdrawalreflex threshold of rats in ARR+Nimodipine group were significantlyhigher than those in the model group from the day 3 after the operation (P<0.05 and 0.01), and were significantlyhigher than those of both in ARR and Nimodipine groups from the day 5 after the operation (P<0.05 and 0.01). analgesiceffectsof ARR+Nimodipine group were better than those of separate ARR and Nimodipine groups.

Conclusion:The aqueous extractfrom ARR combined with Nimodipine has the ideal analgesiceffects.

mechanismof anti-nociceptiveeffectsof Asarum sieboldii Miq. Radix: potentialrole of bradykinin, histamine and opioidreceptor-mediatedpathways

The radix of Asarum sieboldii Miq. (AR) has been used to treatpainand inflammationin Korea. The present study was conducted to gain insights into the mechanismof actionsregarding anti-nociceptiveand anti-inflammatoryactivitiesof AR. Administration of methanol extractof AR causeddramatic anti-nociceptiveeffectsbased on acetic acid writhingand tail-flick assay. When naloxone (Nx) was pre-treated, AR extractfailed to exertsuch anti-nociceptiveeffectin the tail-flick assays.

These resultssuggest that AR extracthave opioid-like activity. It also exertedsignificantanti-inflammatoryeffectsin the rat paw edemaassay. AR extractcausedinhibitionin the bradykinin (BK)/histamine-mediatedileum contractionsof guinea pig. Taken together, these resultsprovideevidencethat the methanol extractof AR exertsanti-nociceptiveand anti-inflammatoryeffectsby activating opioidreceptoras well as by inhibiting bradykinin and histamine-mediatedactions.

painrelievingand protectiveeffectsof Astragalus hydroalcoholic extractin rat arthritismodels

Objectives: The evaluation of the pharmacological profile of the dried 50% hydroalcoholic extract(50%HA) of Astragali radix in two different animal models of articular damage resembling osteoarthritisand rheumatoidarthritis.

Methods: Sodium monoiodoacetate (MIA) or complete Freund’s adjuvant (CFA) was intra-articular injected (day 0) in the rat tibiotarsal jointto induce damages mimicking osteoarthritisor rheumatoidarthritis. painmeasurements (responses to non-noxious and noxious stimuli, spontaneous pain, articular pain) were assessed on days 7 and 14. On day 14, the tibiotarsal joints were explanted in order to measure the diameter and to assess histological evaluations. Furthermore, the plasmatic concentrations of inflammatoryand anti-inflammatorycytokineswere measured.

Results:A single administration of 50%HA (300 mg/kg per os) significantlyreducedboth MIA-inducedpainand CFA-inducedpain(78% and 96% painrelief, respectively). The repeated administration preventedthe development of hypersensitivity on day 14. The haematoxylin/eosin staining revealedthat 50% HA attenuatedjointalterations in MIA-injected rats, and furthermore, the jointinflammatoryinfiltrate was reducedin both models (by about 50%). In CFA-treatedrats, 50%HA lowered the plasmatic levels of the pro-inflammatorycytokinesinterleukin-1ß and tumour necrosis factor-a as well as the jointdiameter.

Conclusion:The 50% hydroalcoholic extractof Astragali radix is a valuablecandidate for the adjuvant treatmentof articular diseases.

analgesicand anti-inflammatoryeffectsof Aucklandia lappa Root extractson Acetic Acid-inducedwrithingin Mice and Monosodium Iodoacetate-inducedosteoarthritisin Rats

Osteoarthritis(OA) is an age-related jointdisease and one of the mostcommon degenerativebone diseasesamong elderlypeople. The currently used therapeuticstrategies relying on nonsteroidalanti-inflammatorydrugs (NSAIDs) and steroids for OA are often associated with gastrointestinal, cardiovascular, and kidney disorders, despite being proveneffective. Aucklandia lappa is a well-known traditional medicine. The root of A. lappa root has several bioactivecompounds and has been in use as a naturalremedyfor bone diseasesand other healthconditions.

We evaluated the A. lappa root extractson OA progression as a naturaltherapeuticagent. A. lappa substantiallyreducedwrithingnumbers in mice inducedwith acetic acid. Monosodium iodoacetate (MIA) was injected into the rats through their knee joints of rats to induce experimental OA, which shows similar pathological characteristics to OA in human. A. lappa substantiallyreducedthe MIA-inducedweight-bearing of hind limb and reversedthe cartilage erosion in MIA rats. IL-1ß, a representative inflammatorymediatorin OA, was also markedly decreasedby A. lappa in the serum of MIA rats. In vitro, A. lappa lowered the secretion of NO and suppressedthe IL-1ß, COX-2, IL-6, and iNOS production in RAW264.7 macrophages activated with LPS. Based on its analgesicand anti-inflammatoryeffects, A. lappa could be a potentialremedial agentagainstOA.

Evaluation of the analgesicand anti-inflammatoryactivitiesof methanolic extractsof the leavesof Averrhoa bilimbi leaves

Objectives:This study was aimed to investigate the analgesicand anti-inflammatoryactivitiesof crude methanolic extractAverrhoa bilimbi leaves.

Materials and Methods:Methanolic extractsof Averrhoa bilimbi leaveswith different concentration were tested for analgesicactivityin mouse model by acetic acid inducedwrithingand anti-inflammatory effectwas tested by carrageenan inducedpaw edemamodel

Results:The extract, at 400 mg/kg, showedhigher analgesicactivity(67.51%) againstacetic acid inducedpainin mice while the standard reference drug Diclofenac sodium exhibited64.33% activityat 10 mg/kg dose. The anti-inflammatoryeffectof the extractwas comparable to reference drug Ibuprofen and the effectwas sustained for 2-4 hr.

Conclusion:Methanolic extractof Averrhoa bilimbi leaveshave moderate analgesicand anti-inflammatoryproperties.

Evaluation of the analgesicand antipyreticactivitiesof ethanolic extractof male flowers(inflorescence) of Borassus flabellifer L. (Arecaceae)

Analgesicand antipyreticeffectsof ethanolic extractof male flowers(inflorescences) of Borassus flabellifer L. (Arecaceae) were investigated at doses 150mg/kg b.w. and 300mg/kg b.w. using acetic-acid inducedwrithing, hot-plate, tail-clip, formalin and yeast-inducedpyrexia tests. oraladministration Borassus flabellifer ethanolic extract(BFEE) producedsignificant(P<0.0001) reductionin no. of writhes inducedby acetic-acid.

Moreover, in hot-plate test, BFEE significantly(P<0.0001) raised the painthreshold at different time of observation (0-60min) in comparison with control. In tail-clip test also the extractcauseda significant(P<0.0001) inhibitionof painat both the doses used. There was a significantdose-dependent inhibitionof both phases of the formalin inducedpainresponse in mice. Tested on yeast-inducedpyrexia in rats, BFEE significantly(P<0.0001) reversedhyperthermia at either dose. The resultsof pharmacological testsperformed in the present study suggest that BFEE possessespotentanalgesicand antipyreticeffects.

anti-inflammatoryand analgesicactivityof different fractionsof Boswellia serrata

The study was designed to investigate the anti-inflammatoryand analgesic effectof different fractionsof Boswellia serrata. The effectof different fractionsof Boswellia serrata were studied using carrageenan inducedpaw edema, acetic acid inducedwrithingresponse, formalin inducedpain, hot plate and tail flick method for studying anti-inflammatoryand analgesic activity, respectively. The different fractionsof B. serrata, essentialoil (10 ml/kg), gum (100 mg/kg, resin (100 mg/kg) oleo-resin (100 mg/kg) and oleo- gum-resin (100 mg/kg) significantlyreduces carrageenan induced inflammationin rats and shows analgesicactivity, as determined by acetic acid inducedwrithingresponse, formalin inducedpain, hot plate and tail flick method.

The different fractionsof B. serrata showedprompt anti-inflammatoryand analgesicactivitydue to the inhibitionof 5-lipoxygenase enzyme.

naturalanti-inflammatoryagentsfor painrelief

The use of both over-the-counter and prescription nonsteroidalmedicationsis frequently recommended in a typical neurosurgical practice. But persistent long-term use safety concerns must be considered when prescribing these medicationsfor chronicand degenerativepainconditions.

This article is a literature review of the biochemical pathwaysof inflammatorypain, the potentially serious side effectsof nonsteroidaldrugs and commonly used and clinically studied naturalalternative anti-inflammatorysupplements. Although nonsteroidalmedicationscan be effective, herbs and dietary supplements may offer a safer, and often an effective, alternative treatmentfor painrelief, especially for long-term use.

analgesicand antipyreticactivitiesof Ethanolic extractof Sappan wood (Caesalpinia sappan L.) leaves

Sappan wood (Caesalpinia sappan L.) is used as an analgesicand antipyreticby the Indonesian people, empirically. The aim of this study was to determine the analgesicand antipyreticactivityof ethanolic extractof sapan wood leavesin Webster mice as experimental animals. The writhingmethod was used to determine the analgesicactivityin acetic acid-inducedmice with mefenamic acid as a positive control. The temperature reductionmethod was used to determine the antipyreticactivityin yeast-inducedmice with paracetamol as a positive control. One-way ANOVA was conducted for statistical analysis, followed by Tukey-Kramer post hoc test. phytochemicalscreening showedthat sappan wood contains alkaloids, flavonoids, saponins, monoterpenoids, and sesquiterpenoids. The optimum dose of analgesicand antipyreticactivitywas 6.3 mg and 8.4 mg/20 g BW of mice, respectively.

The conclusionwas ethanolic extractof sappan wood leaveshas analgesicand antipyreticactivities.

The medicinalusesof Callicarpa L. in traditional Chinese medicine: An ethnopharmacological, phytochemicaland pharmacological review

Ethnopharmacological Relevance : Callicarpa L. (Verbenaceae) has been used for centuries in Traditional Chinese medicine(TCM) for the prevention and treatmentof a wide number of healthdisorderssuch as inflammation, rheumatism, hematuria, fracture, hematemesis, menoxenia, gastrointestinal bleeding, scrofula, etc.

Aims of the review : To assess the scientific evidencefor therapeuticCallicarpa in TCM and to identify future research needs.

Methods : The available information on the ethnopharmacological usesin Chinese medicine, phytochemistry, pharmacology and clinical practice of Callicarpa species was collected via a library and electronic search (PubMed, ScienceDirect, Google Scholar and CNKI).

Results : A variety of ethnomedicaluse of Callicarpa has been recorded in many ancient Chinese books. phytochemicalinvestigation of this genus has resulted in identification of more than 200 chemical constituents, among which diterpenes, triterpenoids and flavonoidsare the predominant groups. The isolates and crude extracthave exhibiteda wide spectrum of in vitro and in vivo pharmacological effectsinvolving anti-inflammatory, hemostatic, neuroprotective, anti-amnesic, antitubercular, antioxidant, antimicrobial and analgesicactivities. Preparations containing Callicarpa species exertedgood efficacyon clinical applications of gynecological inflammation, internal and external hemorrhage as well as acne vulgaris and chronicpharyngitis, etc. From the toxicity perspective, only three Callicarpa species have been assessed.

Conclusion : Pharmacological resultshave validated the use of Callicarpa species in the traditional medicine. As literature demonstrated, terpenoids and flavonoidsare perhaps responsible for mostof the activitiesshown by the plantsof this genus. However, the detailed activecompounds and the underlying mechanismsremain a work in progress. In addition, more attention should be paid to C. nudiflora as well as the domain of rheumatism.

In vitro and in vivo evaluation of pharmacological potentials of Campsis radicans L

Background : Campsis radicans L. is a flowering plantin Bangladesh, traditionally used for the treatmentof several human diseases. In this study, in vitro antioxidant, thrombolytic, membrane stabilizing and in vivo analgesic, hypoglycemic, anti-diarrheal and CNS antidepressant activitiesof organic soluble fractionsof crude methanol extractof C. radicans leafwere investigated using appropriate experimental models.

Methods : The leavesof C. radicans were collected, authenticated, dried and extracted with methanol at room temperature for 30 days. The concentrated methanol extractwas partitioned to petroleum-ether (PESF), dichloromethane (DMSF) and ethyl acetate (EASF) soluble fractions. The antioxidantactivityof these fractionswas determined by DPPH freeradicalscavengingmethod. Total phenoliccontent was determined by the Folin-Ciocalteau’s spectrophotometric method. The thrombolytic activitywas assessed by measuring clot lysis ability whereas the membrane stabilizing activitywas evaluated by heat- and hypotonic solution-inducedhemolysis assay. Tail immersion procedure and acetic acid- inducedwrithingmodel were used to measure the analgesicactivityof C. radicans. The hypoglycemic, anti-diarrheal and CNS antidepressant activitieswere determined by oralglucose tolerance test, castor oil-induceddiarrheal model and thiopental-sodium inducedsleeping time test in mice, respectively.

Results : All the organic soluble fractionsof C. radicans contained phenoliccompounds varying from 6.38 to 60.13 mg of GAE/gm of extractive, while in DPPH assay, EASF showedthe highest freeradicalscavengingactivitywith IC50 is 4.69 µg/ml. The PESF exhibitedhighest thrombolytic activity(57.14% clot lysis) and the DMSF showedmaximum53.95% inhibitionof heat-inducedhemolysis of human RBCs. In both tail immersion and acetic acid inducedwrithingmodels, the PESF, DMSF, EASF at the doses of 200 and 400 mg/kg body weight, induceda significant(P < 0.001) decreasein the painful sensation in mice. substantial(P < 0.05) anti-hyperglycemic activityof test samples was foundin mice loaded with glucose at the same doses mentioned earlier. Castor oil induceddiarrheal test of the plantextractives has shown significanteffectin comparison to control group. In CNS antidepressant activityassay, the test samples were able to reducethe duration of sleep in mice causedby thiopental administration.

Conclusion : All these findingsrevealedthat C. radicans possesssignificantantioxidant, thrombolytic, membrane stabilizing, analgesic, hypoglycemic, anti-diarrheal and CNS antidepressant activities.

oralcapsaicin providestemporary relieffor oralmucositis painsecondary to chemotherapy/radiation therapy

Painfrom oralmucositis afflicts from 40% to 70% of patients receiving chemotherapyor radiation therapy. Current methods of clinical painmanagement (for example, topical anesthetics, systemic analgesics) have limited success. In a pilot study, we examined the ability of oralcapsaicin to providetemporary reliefof oralmucositis pain. Capsaicin, the activeingredientin chili peppers, desensitizes some neurons and has providedmoderate painreliefwhen applied to the skinsurface. oralcapsaicin in a candy (taffy) vehicle producedsubstantialpainreductionin II patients with oralmucositis painfrom cancer therapy.

However, this painreliefwas not complete for mostpatients and was only temporary. Additional research is needed to fully utilize the propertiesof capsaicin desensitization and thus optimize analgesia.

At What Extent Does Cardiospermum Halicacabum relieveschronicjointpainamong elderly? An Experiment in Urban Community of Tamilnadu, India.

Background:One of the majorhealthproblems among elderlyis osteoarthritiswhich leavesthem suffering from chronicjointpain. Prescription of pharmacological measures such as analgesicsto treatthe jointpaincausesmany adverse effectsand non-compliance. This study attempts to inquire the use of herbas a pain-relievingmeasure among elderlyas it does not produce any side effectsand easily available at affordable costs. Objective: To evaluate the effectiveness of Cardiospermum halicacabum leavesSoup on chronicKnee painamong elderlypopulation

Method:Pre-experimental study was conducted among 30 elderlypersons residing at Dharmapuri, South India. Pre-test level of chronicknee painamong elderlywas assessed through Numeric painIntensity Rating Scale. 100ml of freshly prepared Cardiospermum halicacabum leavessoup was given to the participants once in a day for 21 days and then post-test level of chronicknee painwas assessed.

Results:There was significantdifference (p&lt;0.05) foundbetween mean pre-test (7.6 ± 0.83) and post-test (2.73 ± 1.04) painscore. The pretest level of painhas significantassociation (p&lt;0.05) with the occupation, type of work and BMI.

antinociceptiveand anti-inflammatoryactivitiesof extractand two isolated flavonoidsof Carthamus tinctorius L

Ethnopharmacological relevance: Safflower (Carthamus tinctorius L.) has been long used both in the traditional systemand folkmedicineas an analgesicanti-inflammatoryagentin China. The aim of the study was to evaluate the antinociceptiveand anti-inflammatoryactivitiesof hydroalcoholic extract(HE) and two isolated kaempferol glycosides of Carthamus tinctorius L. to provideexperimental evidencefor its traditional use.

Materials and methods: antinociceptiveeffectsof HE, kaempferol 3-O-rutinoside (K-3-R) and kaempferol 3-O-glucoside (K-3-G) were assessed in mice using the acetic acid-inducedwrithingtest, formalin test and cinnamaldehyde test. The anti-inflammatoryeffectsof HE, K-3-R and K-3-G were determined in two animal models: carrageenan-inducedpaw edemaand xylene-inducedear edema.

Results:The HPLC analysis showedthe presence of K-3-R and K-3-G in Carthamus tinctorius L. HE (500 and 1000 mg/kg) as well as K-3-R and K-3-G (150, 300 and 600 mg/kg) producedsignificantinhibitionon nociceptioninducedby acetic acid and formalin. oraltreatmentof HE, K-3-R and K-3-G at all doses significantlyreducedboth the nociceptiveresponse and cinnamaldehyde-inducedpaw edema, effectthat was superior to aspirin. In anti-inflammatorytests, HE and K-3-G significantlyinhibitedthe paw edemaduring the both phases of carrageenan-inducedinflammationwhile K-3-G suppressedthe late phase inflammationonly. HE (400 and 800 mg/kg) and K-3-G (200, 400, 800 mg/kg) producedsignificantdose-dependent inhibitionof xylene-inducedear edemadevelopment. K-3-R only suppressedear edemaformation at a high dose (800 mg/kg).

Conclusion:These resultsdemonstratethat Carthamus tinctorius L. extractpossessremarkable antinociceptiveand anti-inflammatoryactivitieswhich may be due to K-3-R and K-3-G at least in part, supporting the folkloric usage of the plantto treatvarious inflammatoryand paindiseases.

Evaluation of anti-inflammatoryand analgesicactivitiesof extractsfrom herbof Chelidonium majus L.

The aim of the study was to evaluate analgesicactivity(“hot plate” test), anti-inflammatoryactivity(carrageenan-inducedpaw edema) and locomotor activityin rats under the influence of three fractionsof Chelidonium majus herbextract: full water extract(FWE), protein enriched fraction(PEF), and non-protein fraction(NPF). effectsof the fractionson the level of chosen cytokinesand their mRNA levels were also assessed using lipopolysaccharide (LPS) administration as a proinflammatorycue. All fractionsand diclofenac did not affect the locomotor activityof rats in comparison with the control group. FWE and PEF three hours after administration showedstatistically significantanalgesicactivitiescomparable to morphine(p < 0.05). A slight reductionin rat paw edemawas observedafter three (comparable with diclofenac) and six hours in the NPF group. FWE revealeda statistically significantpro-inflammatoryeffectafter three hours in comparison with the control group. Peripheral IL-1 and IL-4 cytokine concentrations were reducedunder FWE and NPF, PEF fractions. The combination of FWE, PEF and NPF together with LPS showedonly the effectsof LPS.

We suggest that protein enriched fraction(PEF) producedcentrally mediated(morphine-like) analgesicaction, whereas the anti-inflammatorypotentialwas shown only after LPS-inducedinflammation. The precise mechanismsinvolved in the production of anti-nociceptiveand anti-inflammatoryresponses of studied fractionsare not completely understood, but they may be causedrather by the presence of protein more than alkaloids-enriched fraction. This fractionof the extractcould be used as an alternative therapyfor the prevention of inflammatory-related diseasesin the future, but further studiesare needed.

analgesiccomponentsof Saposhnikovia Root (Saposhnikovia divaricata)

By activity-oriented separation using the writhingmethod in mice, the analgesiccomponentsof Saposhnikovia root (Saposhnikovia divaricata Schischkin; Umbelliferae) were identified to be chromones, coumarins, polyacetylenes and 1-acylglycerols. Two new components, divaricatol and (3’S)-hydroxydeltoin, were also isolated. The mostpotentanalgesiawas observedin chromones such as divaricatol, ledebouriellol and hamaudol, which inhibitedwrithinginhibitionat an oraldose of 1 mg/kg in mice. Acylglycerols also showedinhibitionsignificantlyat a dose of 5 mg/kg.
In some pharmacological testsusing sec-O-glucosylhamaudol, the compound showedanalgesiaby the tail pressure and the Randall & Selitto methods, and its writhinginhibitionwas not reversedby naloxone.

anti-inflammatoryand Antiosteoarthritiseffectsof Saposhnikovia divaricata ethanol extract: In Vitro and In Vivo studies

Saposhnikovia divaricata Schischkin has been used in traditional medicineto treatpain, inflammation, and arthritis. The aim of this study was to investigate the anti-inflammatoryand Antiosteoarthritisactivitiesof Saposhnikovia divaricata extract(SDE). The anti-inflammatoryeffectof SDE was evaluated in vitro in lipopolysaccharide- (LPS-) treatedRAW 264.7 cells. The antiosteoarthritic effectof SDE was investigated in an in vivo rat model of monosodium iodoacetate- (MIA-) inducedosteoarthritis(OA) in which rats were treatedorallywith SDE (200 mg/kg) for 28 days.

The effectsof SDE were assessed in vivo by histopathological analysis and by measuring weight-bearing distribution, cytokine serum levels, and jointtissue inflammation-related gene expression. SDE showedanti-inflammatoryactivityby inhibiting the production of nitric oxide (NO), prostaglandin E₂ (PGE₂), tumor necrosis factor-a (TNF-a), and interleukin-6 (IL-6) in LPS-inducedRAW 264.7 cells. In addition, SDE promoted recovery of hind limb weight-bearing, inhibitedthe production of proinflammatorycytokinesand mediators, and protectedcartilage and subchondral bone tissue in the OA rat model. Therefore, SDE is a potentialtherapeuticagentfor OA and/or associated symptoms.

antinociceptiveeffectsof intrathecal cimifugin treatment: a preliminary rat study based on formalin test

Background : Cimifugin is one of the componentsof the root of Saposhnikovia divaricata. The extractderived from S. divaricata is traditionally used as an analgesic. This study was conducted to evaluate the analgesiceffectof intrathecal cimifugin in the formalin test.

Methods : Male Sprague–Dawley rats (n = 20) were randomized into four groups for intrathecal administration of 70% dimethylsulfoxide and various doses of cimifugin (100 µg, 300 µg, and 1,000 µg). The typical flinch response after the injection of 5% formalin into the hind paw was assessed in two distinct phases: phase 1 until 10 min, and phase 2 from 10 min to 60 min. ED50 valueswere calculated via linear regression.

Results : Intrathecal cimifugin significantlyreducedthe flinch response in both phases of the formalin test. significantantinociceptiveeffectsof cimifugin were foundwith the dose of 300 µg in phase 1 and the dose of 100 µg in phase 2. The ED50 value(95% confidence intervals) of intrathecal cimifugin was 696.1 (360.8–1,342.8) µg during phase 1 and 1,242.8 (42.0–48,292.5) µg during phase 2.

Conclusion :I ntrathecal cimifugin has an antinociceptiveeffectagainstformalin-inducedpain. Cimifugin has an anti-inflammatoryeffectat low concentrations, and non-inflammatoryanalgesiceffectat higher concentrations.

The essentialoil from the twigs of Cinnamomum cassia Presl alleviatespainand inflammationin mice

Ethnopharmacological relevance: Cinnamomum cassia Presl (Lauraceae) can be foundsouthern China and its barkis commonly used for centuries as ingredientin food and cosmetic industry. The twigs of Cinnamomum cassia Presl is popularly used in China to treatinflammatoryprocesses, pain, menstrual disorders, hypertension, fever etc. The aim of this study is to evaluate the antinociceptiveand anti-inflammatorypropertiesof the essentialoil (EO) from the twigs of Cinnamomum cassia Presl.

Material and methods: The chemical characterization of the EO was performed by gas chromatography coupled with mass spectrometry (GC-MS). The EO doses of 15, 30, and 60 mg/kg were employed in the biological assays. The antinociceptiveeffectsof the EO were evaluated using the models of acetic acid-inducedwrithing, oxytocin-inducedwrithing, and formalin and complete Freund’s adjuvant (CFA) -inducedovert paintests. we also investigated the effectof the EO in painintensity to a mechanical stimulus (mechanical hyperalgesia) after carrageenan by using an electronic version of von Frey filaments. Evaluation of anti-inflammatoryactivitywas based on paw edemainducedby carrageenan (300 µg/25 µL/paw) in mice. The levels of cytokines, NO, and PGE2 in paw skintissue were determined according to instructions. COX-2 and iNOS proteins in paw skintissue were assessed by Western Blot.

Results:The EO (15, 30, and 60 mg/kg) reducedthe number of abdominal writhings inducedby acetic acid with inhibitionof 38.0%, 55.4% and 58.7%, respectively. The EO (15, 30, and 60 mg/kg) also reducedthe number of abdominal writhings inducedby oxytocin with inhibitionof 27.3%, 51.7% and 69.0%, respectively. The EO significantinhibitedthe inflammatory(second phase: 10–30 min) phase of the formalin-inducedpaw flinching and licking at the doses of 15, 30, and 60 mg/kg. The EO at the tested doses of 15, 30, and 60 mg/kg showedinhibitedCFA-inducedpaw flinching and licking. The EO (15, 30, and 60 mg/kg) also inhibitedcarrageenan-inducedmechanical hyperalgesiaand paw edema. It also decreasedthe levels of cytokines(TNF-a, and IL-1ß), NO, and PGE2 in carrageenan-inducedmice paw skintissue. Moreover, Western blot analysis showedthat COX-2 and iNOS expressions in paw skintissue of mice were significantlyreduced.

Conclusion:These resultsdemonstratethat the antinociceptiveand anti-inflammatorypropertiesof the EO from the twigs of Cinnamomum cassia Presl, corroborating its use in folkmedicine.

antinociceptiveeffectOf Cinnamon extractOn Formalin inducedpainIn Rat

Since time memorial, herbalmedicinehas played an importantrole for reliefof various symptoms including painrelief.  Many researchers have focused on the curative as well as antinociceptiveeffectsof herbalextracts. Cinnamon Zeylanicum has long been prescribed in traditional medicinefor the treatmentof inflammatory-related diseasessuch as rheumatisms, bronchitis and muscle pains. However, there is little if any scientific research indicating this effect.Methods: This experimental study was carried out in Shaheed Sadoughi medicalSchool on 25 Wistar Rats (200-300grams) randomly divided into 5 groups. In this study, the analgesiceffectof intraperitoneal administration of hydro-alcoholic Cinnamon extractin different doses (50,100,500mg/kg) was assessed by using Formalin Test (for chronicpain) during 1hr. post Formalin injection.results: Our resultsindicated that cinnamon extractin high dose (500mg/kg) decreasedthe chronicpainintensity in the 2nd phase of formalin test.

This analgesiceffectwas significant(P<0.001) as compared with sham group, but the lower doses (50 &100mg/kg) of cinnamon extractdid not show any analgesiceffecton chronicpainin Formalin Test.conclusion: Data from this study confirms the analgesiceffectof high doses (500mg/kg) of cinnamon extracton chronicpainin Formalin Test which may be due to anti-inflammatoryeffectof this plantmaterial.

analgesic, anti-inflammatoryand venotonic effectsof Cissus quadrangularis Linn.

Cissus quadrangularis, a medicinalplantindigenous to Asia and Africa, is used for many ailments, especially for the treatmentof hemorrhoid. The effectsassociated with hemorrhoid, i.e. analgesicand anti-inflammatoryactivitiesas well as the venotonic effectof the methanol extractof C. quadrangularis (CQ) were assessed in comparison with reference drugs. In the analgesictest, CQ provoked a significantreductionof the number of writhes in acetic acid-inducedwrithingresponse in mice. CQ also significantlyreducedthe licking time in both phases of the formalin test. The resultssuggest peripheral and central analgesicactivityof CQ. In acutephase of inflammationCQ elicited the inhibitoryeffecton the edemaformation of the rats’ ear inducedby ethyl phenylpropiolate as well as on the formation of the paw edemain rats inducedby both carrageenin and arachidonic acid. It is likely that CQ is a dual inhibitorof arachidonic acid metabolism.

In addition, CQ exertedvenotonic effecton isolated human umbilical vein similarly to the mixture of bioflavonoids, i.e. 90% diosmin and 10% hesperidin. The resultsobtained confirmedthe traditional use of C. quadrangularis for the treatmentof painand inflammationassociated with hemorrhoid as well as reducingthe size of hemorrhoids.

An in vivo and in vitro assessment of the anti-inflammatory, antinociceptive, and immunomodulatory activitiesof Clematis terniflora DC. extract, participation of aurantiamide acetate

Aim : Clematis terniflora DC. has been widely used as a traditional Chinese medicinefor the treatmentof tonsillitis, rheumatoidarthritis, and prostatitis. Despite its widespread use in China, there are currently no studiessystematically examined its therapeuticeffectsand mechanismof action. As such, the present study was conducted to evaluate the anti-inflammatory, antinociceptive, and immunomodulatory effectsof C. terniflora DC. using rodent and cellular models.

Methods : The anti-inflammatorypropertiesof the 70% ethanol eluted fractionof the 70% ethanol extractof C. terniflora DC. (EECTD) were evaluated using the xylene-inducedear swellingtest, the carrageenan-inducededemamodel, and the cotton pellet granuloma method. Its antinociceptiveactivitieswere determined using both the acetic acid-inducedwrithingtest and the hot plate assay. In parallel, we conducted an in vitro assay in LPS-inducedRAW264.7 cells to examine the anti-inflammatoryeffectsof EECTD and its purified form, aurantiamide acetate (AA) on inhibitionof nitric oxide (NO) and prostaglandin E2 (PGE2) release.

Results : EECTD (300 mg/kg) significantlyreducedthe number of writhing, extended the painresponse latency, and suppressedxylene-inducedear swelling. Each EECTD treatmentgroup also had significantinhibitionof cotton granulation formation in addition to reducedcarrageenan-inducedpaw edema. EECTD was also shown to alleviatesigns of inflammationin histopathological paw sections. However, it had a less noticeable effecton mouse ear swellingin the delayed type hypersensitivity test. A purified compound was isolated from EECTD and its structure was identified as AA. In vitro experimental resultsshowedthat both EECTD and AA were able to significantlyinhibitthe release of pro-inflammatorycytokinesNO and PGE2 on LPS-inducedRAW264.7 cells.

Conclusion : These resultssuggest that EECTD has significantanti-inflammatoryand antinociceptiveactivities, partially related to one of the activesubstances identified as AA. We hypothesize that these effectsare related to its ability to inhibitthe production of cytokinesNO and PGE2. However, further work will be needed to determine its exact mechanismof action.

naturalProducts for the treatmentof pain: Chemistry and Pharmacology of Salvinorin A, Mitragynine, and Collybolide

Painremains a very pervasive problem throughout medicine. Classical painmanagement is achievedthrough the use of opiates belonging to the mu opioidreceptor(MOR) class, which have significantside effectsthat hinder their utility. Pharmacologists have been trying to develop opioids devoid of side effectssince the isolation of morphinefrom papaver somniferum, more commonly known as opium by Sertürner in 1804. The naturalproducts salvinorin A, mitragynine, and collybolide represent three nonmorphinan naturalproduct-based targets, which are potentselective agonists of opioidreceptors, and emerging next-generation analgesics. In this work, we review the phytochemistry and medicinalchemistry efforts on these templates and their effectson affinity, selectivity, analgesicactions, and a myriad of other opioid-receptor-related behavioraleffects.

Collybolide is a novelbiased agonist of ?-opioidreceptorswith potentantipruritic activity

In recent years, the ?-opioidreceptor(?OR) has become an attractivetherapeutictarget for the treatmentof a number of disordersincluding depression, visceral pain, and drug addiction. A search for naturalproducts with novelscaffolds targeting ?OR has been intensive. Here, we report the discovery of a naturalproduct (Colly) from the fungus Collybia maculata as a novelscaffold that contains a furyl-d-lactone core structure similar to that of Salvinorin A, another naturalproduct isolated from the mint Salvia divinorum. We show that Colly functions as a ?OR agonist with antinociceptiveand antipruritic activity. Interestingly, Colly exhibitsbiased agonistic activity, suggesting that it could be used as a backbone for the generation of noveltherapeuticstargeting ?OR with reducedside effects.

Among the opioidreceptors, the ?-opioidreceptor(?OR) has been gaining considerable attention as a potentialtherapeutictarget for the treatmentof complex CNS disordersincluding depression, visceral pain, and cocaine addiction. With an interest in discovering novelligands targeting ?OR, we searched naturalproducts for unusual scaffolds and identified collybolide (Colly), a nonnitrogenous sesquiterpene from the mushroom Collybia maculata. This compound has a furyl-d-lactone core similar to that of Salvinorin A (Sal A), another naturalproduct from the plantSalvia divinorum. Characterization of the molecular pharmacological propertiesreveals that Colly, like Sal A, is a highly potentand selective ?OR agonist. However, the two compounds differ in certain signaling and behavioralproperties. Colly exhibits10- to 50-fold higher potency in activating the mitogen-activated protein kinase pathway compared with Sal A.

Taken with the fact that the two compounds are equipotentfor inhibiting adenylyl cyclase activity, these resultssuggest that Colly behaves as a biased agonist of ?OR. behavioralstudiesalso support the biased agonistic activityof Colly in that it exhibits~10-fold higher potency in blocking non–histamine-mediateditch compared with Sal A, and this difference is not seen in painattenuation by these two compounds. These resultsrepresent a rare example of functional selectivity by two naturalproducts that act on the same receptor. The biased agonistic activity, along with an easily modifiable structure compared with Sal A, makes Colly an ideal candidate for the development of noveltherapeuticstargeting ?OR with reducedside effects.

Conolidine: A novelplantextractfor chronicpain

Pain, the mostcommon symptom reportedamong patients in the primary care setting, is complex to manage. opioids are among the mostpotentanalgesicsagentsfor managing pain. Since the mid-1990s, the number of opioidprescriptions for the management of chronicnon-cancer pain(CNCP) has increased by more than 400%, and this increased availability has significantlycontributed to opioiddiversion, overdose, tolerance, dependence, and addiction. Despite the questionable effectiveness of opioids in managing CNCP and their high rates of side effects, the absence of available alternative medicationsand their clinical limitations and slower onset of actionhas led to an overreliance on opioids. Conolidine is an indole alkaloidderived from the barkof the tropical flowering shrub Tabernaemontana divaricate used in traditional Chinese, Ayurvedic, and Thai medicine. Conolidine could represent the beginning of a new era of chronicpainmanagement.

It is now being investigated for its effectson the atypical chemokine receptor(ACK3). In a rat model, it was foundthat a competitor molecule binding to ACKR3 resulted in inhibitionof ACKR3’s inhibitoryactivity, causing an overall increasein opiate receptoractivity. Although the identification of conolidine as a potentialnovelanalgesicagentprovidesan additional avenue to address the opioidcrisis and manage CNCP, further studiesare necessary to understand its mechanismof actionand utility and efficacyin managing CNCP.

Conus striatus venomexhibitsnon-hepatotoxic and non-nephrotoxic potentanalgesicactivityin mice

Constant research into the pharmaceutical propertiesof marine naturalproducts has led to the discovery of many potentially activeagentsconsidered worthy of medicalapplications. Genus Conus, which approximately comprises 700 species, is currently under every researcher’s interest because of the conopeptides in their crude venom. Conopeptides have a wide range of pharmacological classes and properties. This research focused on the crude venomof Conus striatus to assess its analgesicactivity, mutagenicity, nephrotoxicity, and hepatotoxicity in mice. The crude venomwas extracted from the conus snails and the protein concentration was determined using Bradford’s method. The analgesicactivityof the venomwas determined using the hot-plate method and standard IFCC method was used to determine the alanine aminotransferase (ALT) and aspartate aminotransferase (AST).

Evaluation of mutagenicity was done using micronucleus assay and the nephrotoxicity of the venomwas determined using Kidney Coefficient and serum creatinine concentration. The maximumtolerable dose (MTD) of the crude venomwas foundto be 75 ppm. The venomexhibitedpotentanalgesicactivityeven higher than the positive control (Ibuprofen). mostof the analgesicdrugs can usually impact damage in the liver and kidneys. However, AST and ALT resultsrevealedthat the venomhas no adverse effectson the liver. Although the venomincreased the incidence of micronucleated polychromatic erythrocytes, making it mutagenic, with MTD concentration’s mutagenicity comparable to the positive control methyl methanesulfonate (MMS). The kidney coefficients, on the other hand, showedno significantdifference between the treatedgroups and that of the untreatedgroup. The serum creatinine also showeda concentration-dependent increase; with MTD treatedmice got the highest creatinine concentration.

However, MTD/2 and MTD/4 showedno significantdifference in creatinine levels with respect to the untreatedgroups. Hence, the nephrotoxicity of the venomwas only evident when used at higher concentration. The venomexhibitedpotentanalgesicactivityindicated that the C. striatus crude venomextractcould have a potentialtherapeuticcomponent as analgesicdrugs that displayed no hepatic damage. This study also suggests that for this venomto be utilized for future medicalapplications, their usage must be regulated and properly monitored to avoid nephrotoxic effect.

The analgesicpropertiesof Corydalis yanhusuo

Corydalis yanhusuo extract(YHS) has been used for centuries across Asia for painrelief. The extractis made up of more than 160 compounds and has been identified as alkaloids, organic acids, volatile oils, amino acids, alcohols, and sugars. However, the mostcrucial biological activeconstituents of YHS are alkaloids; more than 80 have been isolated and identified. This review paper aims to providea comprehensive review of the phytochemicaland pharmacological effectsof these alkaloidsthat have significantties to analgesia.

Evaluation of analgesicand antioxidantpotentialof the leavesof Curcuma alismatifolia

In the present study, the antioxidantand analgesicpotentialof the 80% methanol extractof the leavesof Curcuma alismatifolia Gangnep was evaluated. The extractwas investigated for its antioxidantactivityusing lipid peroxidation, total antioxidantcapacity and reducingpower assays. The extractshowedsignificantantioxidantactivitiesin lipid peroxidation assay compared to the standard antioxidantin a dose dependent manner. In lipid peroxidation assay, the IC50 valuewas foundto be 122.43μg/mL while the IC50 valuefor the reference ascorbic acid was 147.87μg/ml.

Moreover, Curcuma alismatifolia extractshowedstrong total antioxidantcapacity and good reducingpower. The analgesicactivitywas evaluated for its central and peripheral pharmacological actionsusing tail immersion method and acetic acid-inducedwrithingtest in mice respectively. The extract, at the dose of 250 and 500 mg/kg, produceda significant(p < 0.05-0.001) increasein painthreshold in tail immersion methods in a dose dependent manner. In acetic acid-inducedwrithingtest the extract, at a dose of 500 mg/kg, showeda maximumof 60.5% inhibition(p < 0.001) of writhingreactioncompared to the reference drug diclofenac-sodium (75.0%). All experimental resultssuggest the use of this plantfor the treatmentof painand inflammatorydisorder.

A review of therapeuticpotentials of turmeric (Curcuma longa) and its activeconstituent, curcumin, on inflammatorydisorders, pain, and their related patents

Turmeric (Curcuma longa) and its constituent, curcumin, have been used for their therapeuticpropertiesfor a long time. mostof the medicinalimpacts of turmeric and curcumin might be attributed to their anti-inflammatory, antinociceptive, and antioxidanteffects. In the present review, the preventiveand therapeuticpotentials of turmeric and its activeconstituent, curcumin, on inflammatorydisordersand painas well as patents related to their analgesicand anti-inflammatoryeffects, have been summarized to highlight their valueon human health.

A literature review was accomplished in Google Scholar, PubMed, Scopus, Google Patent, Patentscope, and US Patent. Several documents and patents disclosed the significance of turmeric and curcumin to apply in several therapeutic, medicinal, and pharmaceutical fields. These phytocompounds could be applied as a supplementary therapyin phytotherapy, inflammatorydisorderssuch as arthritis, inflammatorybowel diseases, osteoarthritis, psoriasis, dermatitis, and different types of painincluding neuropathicpain. However, because of inadequate clinical trials, further high-quality studiesare needed to firmly establish the clinical efficacyof the plant. Consistent with the human tendency to the usage of phytocompounds rather than synthetic drugs, particular consideration must be dedicated to bond the worth of turmeric and curcumin from basic sciences to clinical applications.

Different Processed Products of Curcumae Radix Regulate pain-Related Substances in a Rat Model of Qi Stagnation and Blood Stasis
Background: Curcumae blood Radix (Yujin) has been widely used to treatQi stagnation and stasis in TCM. According to the Chinese Pharmacopoeia, the tuberous rootsof Curcuma longed L. (i.e., Huangsiyujin, HSYJ) is one of the majorspecies of Yujin. According to the processing theory of TCM, stir-frying HSYJ with vinegar might strengthen the effectof dispersing stagnated hepatoqi to relievepain, and stir-frying HSYJ with wine might strengthen the effectof promotingblood circulation in order to remove blood stasis. However, the mechanismfor the enhancementof clinical efficacyby processing is unclear.
Aim/Hypothesis: This study was aimed at evaluating the effectof different processed products of HSYJ on chemical constituents and pain-related substances to explore underlying mechanismsof HSYJ in treatingpaincausedby Qi stagnation and blood stasis.
Methods: The effectsof different processing methods on the paste yield of water decoction were analyzed, and the content of the main constituents were detected by HPLC. A rat model of Qi stagnation and blood stasis was established by tail clamp stimulation combined with subcutaneous adrenaline injection. After treatmentand intervention with HSYJ and its processed products, β-endorphin(β-EP) and 5-hydroxytryptamine (5-HT) were measured by ELISA, and the expressionof c-fos was evaluated by immunohistochemistry.
Results:After stir-frying with vinegar or wine, the extractyield and curcumin content increased. Compared with model group, raw HSYJ could significantlyimprovethe abnormality of 5-HT in plasma (P < 0.05) and β-EP in brain(P < 0.01). Stir-frying HSYJ with vinegar or wine could significantlyimprovethe abnormality of 5-HT in plasma, β-EP in brain, and the expressionof c-fos (P < 0.01). Stir-frying HSYJ with vinegar could also significantlyincreasethe level of β-EP in plasma (P < 0.05).
Conclusion:These resultsshowedthat different processing methods have certain effectson the chemical constituents of HSYJ, mainly in increasingthe decoction rate and curcumin content. HSYJ and its processed products can reduce5-HT levels, increaseβ-EP levels, and inhibitthe expressionof c-fos in model rats. The effectsof stir-frying HSYJ with vinegar on β-EP levels in plasma was superior to others.

therapeuticeffectsof turmeric or curcumin extracton painand function for individuals with knee osteoarthritis: a systematic review

PurposeTo determine whether supplementation with turmeric or curcumin extracteffectspainand physicalfunction in individuals with knee osteoarthritis(OA). Second, we investigated the therapeuticresponse (painand function) of turmeric compared with non-steroidal anti-inflammatorydrugs (NSAIDs).

MethodsA search was conducted in MEDLINE, Embase, CINAHL and Cochrane Review. Inclusion criteria included randomised controlled trials reporting painand physicalfunction in humans with knee OA comparing turmeric therapywith NSAIDs or no therapy. Two reviewers screened 5273 abstracts. Risk of bias and quality were assessed via Cochrane Collaboration tool and CONSORT (Consolidated Standards of Reporting Trials) 2010, respectively.

Results:Ten studieswere included in the final analysis. Eight had high methodological quality and two were categorised as good with a mean CONSORT quality score of 21.1. Nine studieshad adequate sequence generation and six had adequate allocation concealment. Participants and outcome assessors were blinded in eight studies. Three of the studiescompared turmeric therapyto NSAIDs. All 10 studiesshowedimprovementin painand function from baseline with turmeric therapy(p≤0.05). In three studiescomparing turmeric to NSAIDs, there were no differences in outcome scores (p>0.05). In all studiesthere were no significantadverse events in the turmeric therapygroup.

Conclusion:Compared with placebo, there appears to be a benefit of turmeric on knee OA painand function. Based on a small number of studiesthe effectsare similar to that of NSAIDs. Variables such as optimal dosing, frequency and formulation remain unclear at this time.

Dragon’s blood: Botany, chemistry and therapeuticuses

Dragon’s blood is one of the renowned traditional medicinesused in different cultures of world. It has got several therapeuticuses: haemostatic, antidiarrhetic, antiulcer, antimicrobial, antiviral, wound healing, antitumor, anti-inflammatory, antioxidant, etc. Besides these medicinalapplications, it is used as a coloring material, varnish and also has got applications in folkmagic. These red saps and resins are derived from a number of disparate taxa. Despite its wide uses, little research has been done to know about its true source, quality control and clinical applications.

In this review, we have tried to overview different sources of Dragon’s blood, its source wise chemical constituents and therapeuticuses. As well as, a little attempt has been done to review the techniques used for its quality control and safety.

analgesicand antipyreticactivitiesof alcoholic extractsof Dalbergia Sissoo leaves

Objective:To evaluate the analgesicand antipyreticactivitiesof alcoholic extractof Dalbergia sissoo leaves.

Methods:The peripheral analgesicactivityof Dalbergia sissoo leaves(SLE; 100, 300 and 1000 mg/kg) was studied using acetic acid-inducedwrithingin mice and by Randall-Selitto assay. The central analgesicactivityof SLE was studied using hot-plate method and tail-clip test in mice. The antipyreticactivityof SLE was studied in Brewer’s yeast-inducedpyrexia in rats.

Results:SLE significantlydecreasedthe writhingmovements in mice in acetic acid-inducedwrithingtest. SLE (1000 mg/kg) significantlyincreased the painthreshold capacity in rats in Randall-Selitto assay and the reactiontime in hot-plate test but not in tail-clip test. It also showedsignificantantipyreticactivityin Brewer’s yeast-inducedpyrexia in rats throughout the observation period of 6 h.

[Advance in studieson chemical constitutions, pharmacological mechanismand pharmacokinetic profile of dalbergiae odoriferae lignum]

Dalbergiae Odoriferae Lignum is a traditional Chinese medicine(TCM) commonly used for promotingblood circulation, relievingpainand removing blood stasis. Volatile oil and flavonoid compounds are two main chemical constituents of Dalbergiae Odoriferae Lignum. Modern pharmacological studiesshow that Dalbergiae Odoriferae Lignum has many effects, such as relaxing blood, increasingblood flow of coronary, anti-oxidation, anti-inflammationand antitumor. Dalbergiae Odoriferae Lignum, as a characteristic TCM with the potentialof further development, is generally compatible with other TCMs to treatcardio-cerebral vascular diseases. This article summarizes studieson chemical composition, pharmacological action, pharmacokinetic procfile in vivo and TCM compatibility in recent years, in order to providereferences for further studies.

anti-inflammatoryand analgesiceffectsof Daphne retusa Hemsl

Daphne retusa Hemsl. belongs to the genus Daphne, a member of Thymelaeaceae family. The barks and stems of Daphne retusa are used as a folkloric medicine‘Zhu Shi Ma’ in Western China because of its effectsof detumescence and acesodyne. In this paper, we investigate the anti-inflammatoryand analgesiceffectsof the 75% ethanol extractof the stems and barks of Daphne retusa and different fractionspartitioned with petroleum ether, methylene chloride, ethyl acetate and n-butanol, respectively.
The anti-inflammatoryeffectswere evaluated using xylene-inducedear oedemain mice and carrageenan-inducedpaw oedemain rats, while the acetic acid-inducedwrithingtest and hot-plate test as models for evaluating the centrally and peripherally analgesicactivity. The resultsshowedthe planthas significantanti-inflammatoryand analgesiceffects(P < 0.05–0.01). Meanwhile, the resultof the acutetoxicity test at which the MTD was above 5 g/kg indicates that the plantextractis relatively safe in, and/or non-toxic to, mice. The findingsof these experimental animal studiesindicate that the Daphne retusa ethanol extractpossessesanti-inflammatoryand analgesicproperties, and thus providepharmacological support to folkloric, ethnomedicalusesof ‘Zhu shima’ in the treatmentand/of management of anti-inflammatoryand painful conditions in China.

analgesicand anti-inflammatoryactivitiesof Methanol extractfrom Desmodium triflorum DC in Mice

In this study, we evaluated the analgesiceffectof methanol extractfrom Desmodium triflorum DC (MDT) by using animal models of acetic acid-inducedwrithingresponse and formalin test. The anti-inflammatoryeffectof MDT was investigated by ?-carrageenan-inducedpaw edemain mice. In order to study the anti-inflammatorymechanismof MDT, we detected the activitiesof glutathione peroxidase (GPx) and glutathione reductase (GRd) in the liver, the levels of interleukin-1ß (IL-1ß), tumor necrosis factor (TNF-a), malondialdehyde (MDA) and nitric oxide (NO) in the edemapaw tissue. In the analgesictest, MDT (0.5 and 1.0 g/kg) decreasedthe acetic acid-inducedwrithingresponse and the licking time on the late phase in the formalin test. In the anti-inflammatorytest, MDT (0.5 and 1.0 g/kg) decreasedthe paw edemaat the 3rd, 4th, 5th and 6th hour after ?-carrageenan administration. On the other hand, MDT increased the activitiesof SOD and GRd in liver tissues and decreasedthe MDA level in the edemapaw at the 3rd hour after ?-carrageenan-inducedinflammation. MDT also affected the levels of interleukin-1ß, tumor necrosis factor-a, NO and MDA which were inducedby ?-carrageenan.

The resultssuggested that MDT possessed analgesicand anti-inflammatoryeffects. The anti-inflammatorymechanismof MDT might be related to the decreases in the level of MDA in the edemapaw via increasingthe activitiesof SOD and GRd in the liver, and the NO level via regulating the IL-1ß production and the level of TNF-a in the inflamed tissues.

analgesicand anti-nociceptiveactivityof hydroethanolic extractof Drymaria cordata Willd

Objectives: To study the analgesicand anti-nociceptiveactivityof hydroethanolic extractof Drymaria cordata Willd.

Materials and Methods: Wistar rats and Swiss albino mice were used for studying analgesicand anti-nociceptiveactivityof Drymaria cordata hydroethanolic extract(DCHE) at doses 50, 100 and 200 mg/kg p.o. Various models viz. acetic acid inducedwrithingmodel (female mice), Eddy’s hot plate (mice) and tail flick model (rat) for analgesicstudy and formalin-inducedpaw licking model (mice) were used for anti-nociceptivestudy.

Results:In acetic acid inducedwrithingmodel, effectof DCHE was better than the standard drug- indomethacin 10 mg/kg (p.o.). In the hot plate model, the maximumeffectwas observedat 60 min at a dose of 200 mg/kg p.o., which was higher than the standard drug morphinesulfate (1.5 mg/kg i.p.), whereas in the tail flick model, effectwas comparable with morphinesulfate. In formalin-inducedpaw licking model, administration of DCHE completely abolished the early phase at 100 and 200 mg/kg p.o. and in the late phase, the effectof DCHE (200 mg/kg p.o.) was higher than indomethacin (10 mg/kg p.o.).

Conclusion:DCHE was effectivein both non-narcotic and narcotic models of nociception, suggesting its possible actionvia peripheral and central mechanism. It also abolished the early phase in formalin-inducedpaw licking model, suggesting complete inactivation of C-fiber at higher dose. The activitycan be attributed to the phyto-constituents viz tannins, diterpenes, triterpenes and steroids present in the DCHE extract. In conclusion, DCHE can be developed as a potentanalgesicand anti-nociceptiveagentin future.

Evaluation of Anticonvulsant and analgesicpropertiesof Ethanolic extractof Elettaria cardamomum seedsin Wistar Albino rats

Central and peripheral oxidativestressare importantfactors implicated in the pathogenesis of convulsions and painrespectively. antioxidantpotentialof Elettaria cardamomum (cardamom) seedshas been provenby several studies. phytochemicalanalysis of cardamom seedshave revealedthe presence of phenoliccompounds like flavonoidsand tanninswhich are effectivehydrogen donors capable of reducingoxidativestress. AIMS AND OBJECTIVES : To evaluate the anticonvulsant and analgesicpropertiesof ethanolic extractof Elettaria cardamomum seedsin Wistar albino rats. MATERIALS AND METHODS : A total of 72 healthy Wistar albino rats (180-250 g) of either sex were included in the study and divided into 12 groups consisting of 6 animals each.

The ethanolic extractof Elettaria cardamomum seedswas prepared using cold maceration method and was tested at two graded doses (200 mg/kg BW and 400 mg/kg BW) given orally. Anticonvulsant property was evaluated using Maximal Electroshock [MES] model (standard – Phenytoin 10 mg/kg BW; i.p.) and Pentelenetetrazole [PTZ] model (standard – Sodium valproate 400 mg/kg BW i.p.). analgesicproperty was evaluated using tail warm water immersion method and writing test (standard – morphine5 mg/kg BW i.p.). The resultswere expressedas Mean±SD. Statistical significance among study groups were carried out by using SPSS-16.0 version software, by applying One-way ANOVA followed by Dunnet’s post hoc test. results: The ethanolic extractof cardamom seedsshowedsignificant(p<0.05) decreasein the mean scores of MES inducedseizures at 400 mg/kg BW. 100% protection againstTonic Hind Limb Extension (THLE) was shown by both graded doses of the test drug. The onset of PTZ inducedconvulsions were delayed and the severity, number and scores of seizures were significantlyreducedby cardamom extractat 400 mg/kg BW. At 400 mg/kg BW, there was a significantincreasein the reactiontime in tail warm water immersion test.

There was also significantreductionin total number of writhes and the and the percentage inhibitionof writhes [90.28%] was comparable to the standard drugs. conclusion: The ethanolic extractof Elettaria cardamomum seedspossesssignificantanticonvulsant and analgesicpropertiesin Wistar albino rats at the dose of 400 mg/kg BW.

Epibatidine: a novel(chloropyridyl)azabicycloheptane with potentanalgesicactivityfrom an Ecuadoran poison frog

analgesicactivityof Methanolic extractof the leafof Erythrina variegata

Erythrina variegata (Synonym: Erythrina indica Lamk.; Bengali name- Mandar) is a medium sized deciduous small tree belonging to the family Papilionaceae. The plantgrows all over the Bangladesh.1 The barks are used traditionally as astringent, febrifuge and in leprosy and fever. leavesare anthelmintic, laxative and diuretic. Paste of leavesis applied externally to cure inflammations and to relievepainin the joints. Juice is also used to relieveearache and toothache.1 Previous phytochemical investigation showedthat the stembarkcontains three new isoflavonesand a new isoflavanone.2 Seed contains a fixed oil, fatty acids and lectins.1 Though the plantis traditionally used in many partsof Bangladesh, no scientific report is available to validate the folkloric use.

As a part of our continuing studieson the medicinalplantsof Bangladesh,3-5 the study was undertaken to evaluate the analgesic activityusing acetic acid inducedwrithingand radiant heat tail-flick test in mice models. The leafof the plantE. variegata was collected from Dhaka, Bangladesh in August 2004, and was identified by the experts at the Department of Botany, University of Dhaka. Collected plantparts, after cutting into small pieces, were dried and pulverized into a coarse powder, and stored into an air-tight container.

Characterization of phenoliccompounds from Eugenia supra-axillaris leafextractusing HPLC-PDA-MS/MS and its antioxidant, anti-inflammatory, antipyreticand painkilling activitiesin vivo

Reactiveoxygen species (ROS) are involved in the pathophysiology of several healthdisorders, among others inflammation. polyphenolsmay modulate ROS related disorders. In this work, thirty-two phenoliccompounds were tentatively identified in a leafextractfrom Eugenia supra-axillaris Spring. ex Mart. using HPLC-MS/MS, five of which were also individually isolated and identified. The extractdisplayed a substantialin vitro antioxidantpotentialand was capable of decreasing ROS production and hsp-16.2 expressionunder oxidativestressconditions in vivo in the Caenorhabditis elegans model. Also, the extractshowedhigher inhibitoryselectivity towards COX-2 than COX-1 in vitro with higher selectivity towards COX-2 than that of diclofenac. The extractalso exhibitedanti-inflammatoryproperties: It attenuatedthe edemathickness in a dose dependent fashion in carrageenan-inducedhind-paw odema in rats. In addition, the extractreducedthe carrageenan-inducedleukocyte migration into the peritoneal cavity at the highest dose.

Furthermore, the extractshowedantipyreticand analgesicactivitiesin a mouse model. Eugenia supra-axillaris appears to be a promisingcandidate in treatinginflammation, painand related oxidativestressdiseases.

antinociceptiveactivitiesof 70% methanol extractof Evodiae Fructus (fruitof Evodia rutaecarpa var. bodinieri) and Its alkaloidalcomponents

The effectsof 70% methanol extract(EA-ext) from Evodiae Fructus (EA) consisting of dried fruitsof Evodia rutaecarpa var. bodinieri (Rutaceae) on nocicetive responses were investigated. oraladministration of 50 or 200 mg.kg EA-ext had the same antinociceptiveeffecton writhingresponses as inducedby acetic acid. Its majoralkaloidalconstituents, evodiamine and rutaecarpine also had the antinociceptiveeffect. EA-ext significantlydecreasedthe frequency of licking behavior within a unit of time at the late phase withoutaffecting that of the early phase in the formalin test. EA-ext also increased nociceptivethreshold of the inflamed paw withoutincreasingthat in the non-inflamed paw in the Randall-Selitto test. Although EA-ext inhibitedthe rise of vascular permeability inducedby acetic acid and the increaseof paw edemainducedby carrageenin, it was ineffectiveon nociceptiveresponse in the hot plate test and on locomotor activity.

These resultssuggest that EA possessesantinociceptiveeffectsand its mode of actionmay be mediatedby anti-inflammatoryaction, and that the antinociceptiveconstituents are only partially attributable to alkaloidalcomponentsmentioned above.

antinociceptiveeffectof Ferula assa-foetida oleo-gum-resin in mice

Ferula assa-foetida L. is distributed throughout central Asia and Mediterranean area and grows wildly in Iran and Afghanistan. Asafoetida is an oleo-gum-resin that is the exudates of the rootsof Ferula assa-foetida and some other Ferula species. In Iranian traditional medicine, asafoetida is considered to be sedative, analgesic, carminative, antispasmodic, diuretic, antihelmintic, emmenagogue and expectorant.

The aim of this study was to evaluate the antinociceptiveeffectof asafoetida in mice. The analgesicactivityof asafoetida (25, 50 and 100 mg/kg) was compared with that of sodium diclofenac (30 mg/kg) or morphinesulfate (8 mg/kg) by using hot plate and acetic acid inducedwrithingtests. In hot plate test, the percentage of maximumpossible effect(%MPE) againstthe thermal stimulus at 15 min post treatmenttime point for all doses of asafoetida was significantlygreater than the control group. The number of writhes in all three doses of asafoetida was significantlyless than the control group. GraphPad Prism 5 software was used to analyze the behavioralresponses. Data were analyzed using repeated measure one-way ANOVA and P<0.05 was considered as the significantlevel. According to our findings, asafoetida exhibiteda significantantinociceptiveeffecton chronicand acutepainin mice.

These effectsprobably involve central opioidpathwaysand peripheral anti-inflammatoryaction.

Himalayan Ficus palmata L. fruitextractshowedIn Vivo Central and Peripheral analgesicactivityInvolving COX-2 and Mu opioidreceptors

Analgesicdrugs like morphineand non-steroidal anti-inflammatorydrugs exhibitseveral harmful effects. Here, we show for the first time the analgesicactivityof Ficus palmata L. fruitextract(FPFE) on different analgesicrat models along with the in silico studiesof some of the main phytochemicals of this plant. We performed in vivo painmodels, along with in silico docking studiesagainstthe activesite of COX-2 protein and mu-opioidreceptors. A significant(p < 0.05) analgesiceffectof FPFE was observed, and it was foundthat rutin has good pose and score as compared to diclofenac and morphinan antagonist(X-ligand), and psoralen has binding affinity almostequal to diclofenac, but a lower binding affinity as compared to rutin.

The resultsprovedthat F. palmata fruitshave the potentialto amelioratepainful conditions.

Anil kumar et al., 2011 studied the potentanalgesicactivityof Flemingia strobilifera at the dose levels of 300, 500 and l000 mg/kg. The Flemingia strobilifera showedsignificantanalgesicactivityat low dose of 300 mg/kg even in the first hour of the test. The analgesicactivityshown by Flemingia strobilifera at 300 mg/kg was almost comparable to that producedby acetylsalicylic acid, while at the dose levels of 500 mg/kg and 1000 mg/kg. Flemingia strobilifera showedbetter analgesiceffectthan the reference drug and at the dose level of l000 mg/kg the duration and intensity of analgesiawas also greater than acetylsalicylic acid. The activitywas also evaluated by Tail flick method (Chen et al.,1991).

A comparative study of analgesicproperty of whole plantand fruitextractsof Fragaria vesca in experimental animal models

The aim of the study was to compare the analgesicactivitiesof ethanolic extractof fruitsand whole plantof Fragaria vesca in experimental animal models. The extractswere prepared by percolation method and oraltoxicity testing was performed as per OECD guidelines. analgesicactivitywas assessed by tail flick method (for central action) and acetic acid-inducedwrithingtest (for peripheral action). fruitextract, whole plantextractand aspirin showedsignificantanalgesicactivity, both central and peripheral, as compared to control (p<0.01).

Although fruitextractat dose of 500 mg/kg showedbetter activitythan 250 mg/kg (p<0.05). analgesicactivitiesof fruitextract250 mg/kg and whole plantextract500 mg/kg were almostequivalent while aspirin was mostpotentamong all with significantlygreater

anti-inflammatoryand analgesicactivitiesof ethanolic extractof Fumaria capreolata

Fumaria capreolata is used in traditional medicinefor its gastrointestinal, hepatoprotective, and anti-inflammatoryactivities. The aim of the present study was to investigate the anti-inflammatoryand the analgesiceffectsof the ethanolic extractof Fumaria capreolata (EFC) in mice. anti-inflammatoryactivitywas evaluated by using the xylene-inducedear edemaand multi-application of TPA inducedchronicinflammation, whereas acetic acid-inducedabdominal constrictions and formalin-inducedlicking and biting were used to determine antinociceptiveeffects. The crud extractof Fumaria capreolata (500 and 250 mg/kg) produceda significantinhibitionof ear edemain two models of acuteand chronicinflammation, and produceda significantreductionof the number of writhes. Also, in the formalin test, EFC reducedboth neurogenicand inflammatoryphases.

These findingssuggest the aerialpartsof Fumaria capreolata exhibitspotentanti-inflammatoryand analgesicactivitieson chemical behavioralmodels of nociceptionand inflammationin mice.

Preliminary phytochemicalscreening and evaluation of analgesicactivityof methanolic extractof rootsof Gentiana Kurroo Royle in experimental animal models

The methanolic extractof rootsof Gentiana kurroo Royle (Gentianaceae) an importantand endemic medicinalplantof Kashmir Himalaya was screened for the presence of various bioactiveplantmetabolites and analgesicactivity(using Eddy’s hot plate method and acetic acid-inducedwrithingtest in Swiss albino mice at an oraldose of 250 and 500 mg/kg body weight). Diclofenac sodium (10 mg/kg b.w) was used as standard drug, whereas the vehicle (0.9% normal saline) was used as negative control. The phytochemicalanalysis revealedthe Presence of tannins, alkaloids, saponins, cardiac glycosides, terpenes, flavonoids, phenolics, and carbohydrates. The extractshowedstastically significant(P<0.05) analgesicactivityin a dose-dependent manner, which were comparable with standard analgesicdrug. In acetic acid-inducedwrithingtest, the doses of 250 and 500 mg/kg b.w produced63.38% and 73.70% inhibitionof writhingreflex respectivelyas compared with the standard drug, which showed71.61% inhibition. In eddy’s hot plate method the extractshowedsignificant(P<0.05) increasein reactiontime at different time of observation (0-120 min) in comparison with control.

The study clearly indicate that the crude methanolic root extractof Gentiana kurroo possespotentanalgesicactivity, which has providedsome justification for the folkloric use of the plantas stomach-ache, pain, and anti-inflammatory.

Comparison of outcome measures during treatmentwith the proprietary Harpagophytum extractDoloteffin® in patients with painin the lower back, knee or hip

Besides checking estimates of effectiveness and safety of using the proprietary Harpagophytum extractDoloteffin^®, this postmarketing surveillance compared various disease-specific* and generic** measures of effect.

We enrolled 250 patients suffering from nonspecific low back pain(Back group: n = 104) or osteoarthritic painin the knee (Knee group: n = 85) or hip (Hip group: n = 61). They took an 8-week course of Doloteffin^® at a dose providing60 mg harpagoside per day. The measures of effecton painand disability included the percentage changes from baseline of established instruments (Arhus low back painindex*, WOMAC index*, German version of the HAQ**) and unvalidated measures (total painindex*, three score index*, the patient’s global assessment** of the effectiveness of treatment). Patients also received a diary for the daily recording of their painand any additional treatments for it.

The three groups differed in age, weight and characteristics of initial pain. 227 patients completed the study. Multivariate analysis confirmedthat several dimensions of effectwere recorded by the several outcome measures but, in all groups, both the generic and disease-specific outcome measures improvedby week 4 and further by 8. In multivariable analysis, the improvementtended to be more when the initial painand disability score was more: older patients tended to improveless than younger, the hip group tended to improveconvincingly more than the back group, whereas the improvementin the knee group was less readily differentiated from that in the back group. The subgroup of Back patients who required NSAIDs during the 8 weeks used significantlymore per patient than patients in the other two groups, but that requirement also declined more with time. About 10% of the patients suffered from minor adverse events that could possibly have been attributable to Doloteffin^®.

Between 50% and 70% of the patients benefitted from Doloteffin^® with few adverse effects. Thus, Doloteffin^® is well worth considering for osteoarthritic knee and hip painand nonspecific low back pain.

effectiveness of Harpagophytum extractWS 1531 in the treatmentof exacerbation of low back pain: a randomized, placebo-controlled, double-blind study

Two daily doses of oralHarpagophytum extractWS 1531 (600 and 1200, respectively, containing 50 and 100 mg of the marker harpagoside) were compared with placebo over 4 weeks in a randomized, double-blind study in 197 patients with chronicsusceptibility to back painand current exacerbations that were producing painworse than 5 on a 0–10 visual analogue scale. The principal outcome measure, based on pilot studies, was the number of patients who were painfreewithoutthe permitted rescue medication(tramadol) for 5 days out of the last week.

The treatmentand placebo groups were well matched in physicalcharacteristics, in the severity of pain, duration, nature and accompaniments of their pain, the Arhus low backpainindex and in laboratory indices of organ systemfunction. A total of 183 patients completed the study. The numbers of pain-freepatients were three, six and 10 in the placebo group (P), the Harpagophytum 600 group (600) and the Harpagophytum 1200 group (1200)respectively(P=0.027, one-tailed Cochrane–Armitage test). The majority of responders’ were patients who had suffered less than 42 days of pain, and subgroup analyses suggested that the effectwas confined to patients with more severeand radiating painaccompanied by neurological deficit. However, subsidiary analyses, concentrating on the current paincomponent of the Arhus index, painted a slightly different picture, with the benefits seeming, if anything,to be greatest in the 600 group and in patients withoutmore severepain, radiation or neurological deficit. Patients with more paintended to use more tramadol, but even severeand unbearable painwould not guarantee that tramadol would be used at all, and certainly not to the maximumpermitted dose.

There was no evidencefor Harpagophytum-related side-effects, except possibly for mild and infrequent gastrointestinal symptoms.

A study on analgesicactivityof Holarrhena antidysenterica leaves

The plantHolarrhena antidysentericacommonly known as ‘Kutaja’ belongs to the family Apocynaceae,is a small shrub or small tree evergreen in nature. The plantis medicinally importantwhich is used tocure various diseaseslike diarrhea, dysentery, piles, biliousness and also with potentantioxidantactivity.The analgesicactivityof plantHolarrhena antidysentericawas evaluated by using the petroleum ether,chloroform and ethanolic extractsat the dose of 300, 300 and 250 mg/kg body weight respectivelyin thealbino mice. The study was conducted as per the acetic acid inducedwrithingmethod. The ethanolicextractshowedsignificantanalgesicactivitywhen compared to the standard Aspirin at the dose of 150mg/kg of body weight.

The findingsindicated that the ethanolic extractexhibitedpotentanalgesic activitycomparable to that of the standard drug

analgesicand anti-inflammatoryactivitiesof an Aqueous extractof Hydrocotyle batrachium Hance in Mice

Background//Purpose : To investigate the analgesicand anti-inflammatoryeffectsof a water extractof Hydrocotyle batrachium Hance (HBW) in mice.

Methoods : The analgesiceffectsof HBW were investigated by measuring the acetic acid-induced writhingresponse and the hind paw licking time following formalin injection. λ-Carrageenan (CARR)-inducedpaw edemawas studied to explore the anti-inflammatoryeffectof HBW.

Results : Treatmentof male ICR mice with HBW (100, 500, 1000 mg/kg) inhibitedthe writhing response in a dose-dependent manner. The inhibitoryeffectof HBW at a dose of 1000 mg/kg was similar to that of indomethacin at a dose of 10 mg/kg. HBW significantlyinhibitedthe degree of formalin-inducedpainin the late phase. HBW (500, 1000 mg/kg) also inhibitedthe development of paw edemainducedby CARR. The HPLC analysis revealedthat rutin was an important bioactivecompound in HBW.

Conclusion : HBW appears to have analgesicand ant-inflammatoryactivities.

Evaluation of analgesicand anti-inflammatoryactivitiesof Hydrocotyle umbellata L., Araliaceae (acariçoba) in mice

The Hydrocotyle umbellata L. is a specimen of the Araliaceae family popularly known as acariçoba. Its indications in folkmedicineinclude treatmentof skinulcers, and rheumatism. The aim of this study was to evaluate the antinociceptiveand anti-inflammatoryactivitiesof the ethanolic extractfrom acariçoba’s underground parts(EEA). EEA reducedthe nociceptiveresponse of the animals as evaluated in the acetic acid-inducedwrithingtest and in both phases of formalin test. EEA also presented a supraspinal analgesicactivityby increasingthe painlatency in the hot plate test.

Moreover, EEA reducedthe leukocytes migration and plasma extravasation to pleural cavity in the carrageenan-inducedpleurisy, besides reducingthe edemainducedby carrageenan until the second hour and also the edemainducedby dextran. In conclusionour resultsshowedthat EEA of H. umbellata L. presents analgesicand anti-inflammatoryactivities, and that a blockade of activityor reductionin the release of different mediators, such as histamine and serotonin, could be involved in these pharmacologic effects.

Hypericum perforatum (St John’s wort) beyond depression: A therapeuticperspective for painconditions

Ethnopharmacological Relevance : Hypericum perforatum L. (Hypericaceae), popularly called St. John’s wort (SJW), has a rich historical background being one of the oldest used and mostextensively investigated medicinalherbs. Many bioactivitiesand applications of SJW are listed in popular and in scientific literature, including antibacterial, antiviral, anti-inflammatory. In the last three decades many studiesfocused on the antidepressant activityof SJW extracts. However, several studiesin recent years also described the antinociceptiveand analgesicpropertiesof SJW that validate the traditional usesof the plantin painconditions.

Aim of the review : This review providesup-to-date information on the traditional uses, pre-clinical and clinical evidenceon the painrelievingactivityof SJW and its activeingredients, and focuseson the possible exploitation of this plantfor the management of pain.

Materials and methods : Historical ethnobotanicalpublications from 1597 were reviewed for finding local and traditional uses. The relevant data on the preclinical and clinical effectsof SJW were searched using various databases such as PubMed, Science Direct, Scopus, and Google Scholar. planttaxonomy was validated by the database plantlist.org.

Results : Preclinical animal studiesdemonstratedthe ability of low doses of SJW dry extracts(0.3% hypericins; 3–5% hyperforins) to induce antinociception, to relievefrom acuteand chronichyperalgesic states and to augment opioidanalgesia. Clinical studies(homeopathic remedies, dry extracts) highlighted dental painconditions as a promisingSJW application. In vivo and in vitro studiesshowedthat the main componentsresponsible for the painrelievingactivityare hyperforin and hypericin. SJW analgesiaappears at low doses (5–100 mg/kg), minimizing the risk of herbal-drug interactionsproducedby hyperforin, a potentinducer of CYP enzymes.

Conclusion : Preclinical studiesindicate a potentialuse of SJW in medicalpainmanagement. However, clinical research in this field is still scarce and the few studiesavailable on chronicpainproducednegative results. Prospective randomized controlled clinical trials performed at low doses are needed to validate its potentialefficacyin humans.

Comparative Evaluation of analgesic, antipyretic& anti-inflammatoryeffectsof Various extractsof Dried fruitof Illicium verum Hook.f (Star anise) in Rodents

The current investigation was designed to evaluate the analgesic, antipyretic, and anti-inflammatoryeffectsof various extracts(methanol, ethanol, and aqueous) of dried fruitof Illicium verum hook.f, using 3 different doses (150, 250, and 350 mg/kg p.o) to verify the traditional usesof this spice. In the hot plate model of analgesia, ethanol extractshoweda significantreductionin painin a dose-dependent manner compared to the control group. The maximumeffectwas observedat 350 mg/kg dosage i.e., 16.90±0.17 s compared to the control group i.e., 5.03±0.05 s. The antipyreticactivitywas assessed in rats by Brewer’s yeast induction. The methanol and ethanol extractsproduceda significantreductionin rectal temperature compared to the control group throughout the three doses.

The maximumeffectwas observedat 350 mg/kg dosage of ethanol extracti.e., 37.1±0.8* compared to the control i.e., 39.1±0.3. In the paw edemamodel, methanol and ethanol extractsdisclosed a significantreductionin paw edemaat 350 mg/kg of dose. The maximumeffectwas observedat 350 mg/kg dosage of ethanol extracti.e., 0.25±0.23* compared to the control i.e., 0.97±0.4. In a behavioralstudy, locomotor activity(rearing) and exploratory activity(grooming) in mice was reducedsignificantlyat higher doses (350 mg/kg p.o) involving the three extracts.

However, scratching was increased non-significantlyat all doses compared to the control group. This study concluded that various extractsof Illicium verum hook.f showedsignificantanalgesic, antipyretic, and anti-inflammatoryeffectsat different doses in a dose-dependent manner with varying potencies. The ethanol extractwas foundto be more potentamong all, followed by methanol and aqueous extracts, whereas maximumeffectswere observedat 350 mg/kg of dose.

antinociceptiveactivityof methanol extractof flowersof Impatiens balsamina

Ethnopharmacological Relevance : Impatiens balsamina Linn. (Balsaminaceae), an annual herblocally called “Dopati”, is cultivated as an ornamental garden plantin Bangladesh. flowersof the plantare used in folkmedicineto treatlumbago, neuralgia, burns and scalds.

Aim of the study: This study evaluated the antinociceptiveeffectof the methanol extractof I. balsamina flowers(MIB).

Materials and methods : The extractwas evaluated for antinociceptiveactivityusing chemical- and heat-inducedpainmodels such as acetic acid-inducedwrithing, hot plate, tail immersion and formalin test. To verify the possible involvement of opioidreceptorin the central antinociceptiveeffectof MIB, naloxone was used to antagonize the effect. The effectof MIB on central nervous system(CNS) was also studied using hole cross and open field tests.

Results : MIB demonstratedstrong and dose-dependent antinociceptiveactivityin all the chemical- and heat-inducedmice models (p<0.05). These findingsimply the involvement of both peripheral and central antinociceptivemechanisms. The use of naloxone confirmedthe association of opioidreceptorsin the central antinociceptiveeffect. MIB also showedsignificantcentral nervous systemdepressant effect(p<0.05).

Conclusion : This study reportedthe peripheral and central antinociceptiveactivityof the flowersof I. balsamina and rationalized the traditional use of the flower in the treatmentof different painful conditions.

antioxidant, analgesic, anti-inflammatoryand antipyreticproperties, and toxicity studiesof the aerialpartsof Imperata cylindrica (L.) Beauv.

Imperata cylindrica (L.) Beauv. (Poaceae family) is a perennial weed growing in tropical and subtropical areas and it is used in several herbalpreparations to treatspecific pathologic factors inducingpain. This work aimed to determine the in vitro antioxidantand in vivo anti-inflammatory, analgesicand antipyreticactivitiesof the aerialpartsof this plant. The methanol extract(MEIC) was used for (i) phytochemicalfingerprint by High-Performance Liquid Chromatography (HPLC), (ii) total phenoliccontent (TPC) evaluation by the Folin-Ciocalteu colourimetric method, (iii) 1,1-diphenyl-2-picrylhydrazyl (DPPH) freeradicalscavengerspectrophotometric assay, (iv) antioxidantcapacity by Ferric reducingantioxidantPower (FRAP) assay, (v) analgesicactivityevaluated with the acetic acid-inducedwrithingtest, (vi) anti-inflammatoryactivityevaluation by carrageenan-inducedpaw oedema, (vii) antipyreticeffecton lipopolysaccharide (LPS)-inducedfever in rats, and (viii) acuteand sub-chronictoxicity in mice.

The MEIC presented an average rate of TPC (1920.63 ± 360.62 mgGAE/100 g of dry weight (DW)), which is mostlyrepresented by tannins(37.30%), organic acids (32.84%) and flavonols (10.88%). The DPPH freeradicalscavengerspectrometric assay showedthe antioxidantcapacity of the MEIC (IC50 = 192.07 ± 0.78 µg/mL) confirmedby the FRAP assay results(29.60 ± 0.55 mmol Fe2+/Kg of DW). The MEIC decreasedsignificantlythe number of writhingin a dose-dependent manner (p < 0.01) showing its analgesicactivity; the extractinhibitedthe inflammationin a dose-dependent manner at the first stage (1st h, p < 0.01) and the second stage (3rd h, p < 0.001) post carrageenan induction and it demonstratedan antipyreticactivityby lowering the body temperature (Tb) dose-dependently post LPS induction (i.p. route) and time-dependently at the dose of 200 mg/kg (p < 0.001) in mice. Moreover, the acuteand sub-chronictoxicity in mice did not reveal any signs of toxicity and any changes in targeted biochemical and haematological parameters. The quantified phytocompounds could be at the origin of these pharmacological activities.

These findingssupport the beneficial use of this plantto alleviatepains and fever in inflammatoryor other diseases. Further studieson the isolation of the bioactivecompounds and their actionmechanismsshould be carried out to confirmthese results.

analgesicand anti-inflammatoryactivitiesof Imperata cylindrica

The chloroform extractof the rootsof Imperata cylindrica showedsignificant(p<0.001) antinocipetiveactivityin the acetic acid induce writhingmodel with 27.33 and 48.06% inhibitionof writhingresponse at 150 and 300 mg/kg body weight. The analgesicactivityin the radiant heat tail-flick model in mice also showedsignificant(p<0.01) increasein tail flick latency in a dose dependent manner (r=0.089). However, the anti-inflammatoryactivityin carrageenan inducedrat paw inflammatoryedemashowedno significantreduction.

The analgesiceffectof the Ethanol extractof the Cogon Grass Rhizome
(Imperata Cylindrica (L.) Beauv.) of Mice (Mus musculus)

Indonesia has known some traditional medicine. One of the plantsused for traditional medicineis Imperata cylindrica (L.) Beauv. The new research has been foundflavonoidsin cogon grass rhizome. flavonoidsmight be to inhibitoryactionon cyclooxygenase synthesis. The aims of this research were to find out the existences of analgesiceffectof cogon grass rhizome (Imperata cylindrica (L.) Beauv.) etha- nol extracton male mice. Laboratory experimental research with a complete randomized design were done with five groups and five replications to each group.

The treatmentapplied for those groups were: negative control (CMC 1% 0,2 ml/20 g BW), positive control (asetosal 5 mg/20 g BW), and goups A, B, and C respectivelyto get the ethanol extractof the cogon grass rhizome dose of 1 mg/ 20 g BW, 2 mg/ 20 g BW and 4 mg/20 g BW. The painstimulus was given 15 minutes after treatmentwith the animal placed on a hotplate with temperature 550 C. Animals gave a response in the form licking legs. Interval between stimulus delivery and the occurrence of painwas called reactiontime response. analgesic response was expressedpositive if the reactiontime after the test material was equal or greater than reactiontime of positive control group or greater than three times the normal reactiontime. The result of this research indicated that the ethanol extractof Imperata cylindrica (L.) Beauv. rhizome has analge- sic effecton male mice.

There were significantdifferences statistically between the groups extract4 mg/ 20 g BW mice with the other treatmentgroups.

Anti-diarrhoea and analgesicactivitiesof the methanol extractand its fractionsof Jasminum amplexicaule Buch.-Ham. (Oleaceae)

Jasminum amplexicaule Buch.-Ham. (Oleaceae) has been commonly used in the traditional medicinein dysentery, diarrhoea and bellyache in China. In the present work, the methanol extractof Jasminum amplexicaule and different fractionsof this extractwere studied for anti-diarrhoea and analgesicactivities. The anti-diarrhoea activitieswere investigated using castor oil-induced, magnesium sulphate-induceddiarrhoea models, antienteropooling assay and gastrointestinal motility models in mice. The analgesicactivitieswere studied using hot-plate, writhingand formalin models in mice. At the doses of 100, 200 and 400 mg/kg, the methanol extract(ME) showedsignificantand dose-dependent anti-diarrhoea and analgesicactivityin these models. The chloroform fraction(CHF), ethyl acetate fraction(EAF) and the residual methanol fraction(RMF) exhibitedsimilar activityusing a dose of 200 mg/kg in these models.

The pharmacological activitiesof the n-butanol fraction(BUF) were lesser than the ME extractand other fractions. These resultsmay support the fact that this plantis traditionally used to cure diarrhoea and pain.

antinociceptive, anti-inflammatoryand acuteToxicity effectsof Juglans Regia L. leavesin Mice

Background: Juglans regia leaveshave been used in folkmedicineto alleviateinflammatorydiseases. This study investigates the antinociceptive, anti-inflammatoryand acutetoxicity effectsof Juglans regia L. leavesin mice.

Methods: 351 Male and female albino mice were divided into negative (saline), positive (morphineor diclofenac) controls as well as test groups (n=6-8). The acute(intraperitoneally) toxicity was evaluated for 2 days. antinociceptiveactivitieswere done using hot-plate and writhingtests. anti-inflammatoryeffectswere studied using xylene inducedear edemaand cotton pellet tests.

Results: The LD50 valuesof J. regia aqueous and ethanolic extrats were 5.5 and 3.3 g/kg, respectively. The aqueous (2.87 and 1.64 g/kg) and ethanolic (2.044 and 1.17 g/kg) extractsshowedantinociceptiveactivityin hot-plate test. The pretreatmentof naloxone (2 mg/kg, s.c.) did not inhibitthe extractsactivities. The extractsexhibitedantinociceptiveactivityin writhingtest, which were not blocked by naloxone. In xylene test, both extractsshowedanti-inflammatoryactivityin some doses. The extractsshowedanti-inflammatoryactivityagainstthe chronicinflammation.

Conclusion:J. regia leavesdemonstratedantinociceptiveeffectthrough non-opioidreceptorsand anti-inflammatoryeffectagainstacuteand chronicinflammation. The extractsof J. regia could be considered as a promisinganalgesicand anti-inflammatoryagentsagainstdiseasessuch as rheumatoidarthritis.

analgesicand anti-inflammatoryeffectsand molecular mechanismsof Kadsura heteroclita stems, an anti-arthritic Chinese Tujia ethnomedicinalherb

Ethnopharmacological relevance : Rheumatoidarthritis(RA) is a chronicautoimmune disease characterized by failure of spontaneous resolution of inflammation. The stemof Kadsura heteroclite (KHS) is a well-known anti-arthritic Tujia ethnomedicinalplant, which named Xuetong in folk, has long been used for the prevention and treatmentof rheumatic and arthritic diseases.

Aim of the study : The analgesicand anti-inflammatoryeffectsand the potentialmechanismsbehind such effectsof KHS would be investigated by using different animal models.

Materials and methods : The abdominal writhingepisodes of mice inducedby intraperitoneal injection of acetic acid and the tail-flick response inducedby radiant heat stimulation were used to evaluate the analgesiceffectof KHS. The number of abdominal writhingepisodes of mice and the latency of tail-flick in rats were measured and recorded. In acuteinflammatorymodels, the ear edemaof mice was inducedby applying xylene on the ear surface, while the paw edemaof male and female rats was inducedby subcutaneous injection of carrageenan into the right hind paws of animals. The carrageenan-inducedpaw swellingin rats were selected as an anti-acuteinflammatorymechanismof KHS. Serum levels of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor (TNF-a) were measured by ELISA, and protein expressionof cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were detected by Western blot.

Results :The maximal tolerated single dose of KHS was determined to be 26 g/kg in both sexes of mice. Pharmacological studiesshowedthat KHS at the dose of 200 mg/kg significantlyprolonged the reactiontime of rats to radiant heat stimulation and suppressedabdominal writhingepisodes of mice inducedby intraperitoneal injection of acetic acid. KHS at the dose of 200, 400, and 800 mg/kg, showeddose-dependent inhibitionof xylene-inducedear swellingin mice. KHS at the dose of 100, 200, 400, and 800 mg/kg demonstrateddose- and time-dependent suppression of paw edemainducedby subcutaneous injection of carrageenan in both all rats. Mechanistic studiesrevealedthat the anti-inflammatoryeffectof KHS was associated with inhibitionof the production of pro-inflammatorycytokinesIL-1ß, IL-6, and TNF-a and effectivelydecreasedthe expressionof COX and iNOS proteins in the carrageenan-injected rat serum, paw tissues and inflammatoryexudates. The positive reference drug, rotundine at a dosage of 100 mg/kg and indomethacin at a dosage of 10 mg/kg were used in both mice and rat models.

Conclusion :These resultssuggested that KHS has significanteffectson analgesiaand anti-inflammationwith decreasing the pro-inflammationcytokinesof IL-1ß, IL-6, and TNF-a and inhibiting the proteins expressionof COX-2 and iNOS.

Lactoferrin and Its potentialImpact for the reliefof pain: A Preclinical Approach

Painis one of the mostdisabling symptoms of several clinical conditions. Neurobiologically, it is classified as nociceptive, inflammatory, neuropathicand dysfunctional. opioids and nonsteroidalanti-inflammatorydrugs (NSAIDs) are conventionally prescribed for the treatmentof pain. Long-term administration of opioids resultsin the loss of analgesicefficacy, leading to increased dosage, tolerance, and addictionas the main drawbacks of their use, while the adverse effectsof NSAIDs include gastric ulcer formation, intestinal bleeding, acutekidney injury, and hepatotoxicity. Lactoferrin is an iron-binding, anti-inflammatoryglycoprotein that displays analgesicactivitiesassociated, in part, by interacting with the low-density lipoprotein receptor-related protein (LRP), which may resultin the regulation of the DAMP-TRAF6-NFκB, NO-cGMP-ATP K⁺-sensitive channel and opioidreceptorsignaling pathways.

This review summarizes and discusses for the first time the analgesiceffectsof lactoferrin and its presumable mechanismsbased on pre-clinical trials. Given its anti-nociceptiveand anti-inflammatoryproperties, lactoferrin may be used as an adjunct to enhancethe efficacyand to decreasethe tolerogenic effectsof canonical therapeuticdrugs prescribed for paintreatment.

STUDY OF analgesicAND ANTI inflammatoryACTIVITY FROM plantextractsOF LACTUCA SCARIOLA AND ARTEMISIA ABSINTHIUM

Seedsand samples of stems from the two medicinalplants, Lactuca scariola and Artemisiaabsinthium respectivelywere extracted in absolute methanol to determine their analgesicand anti-inflam-matory activity. The analgesicactivitywas assessed on intact mice by tail flick latency in tail immersionmethod. The anti-inflammatoryactivitywas estimated volumetrically by measuring the mean increasein hindpaw volume of rat with the help of plethysmometer. Acetylsalicylic acid in the dose of 300 mg/kg is used asstandard drug. Both plantextractswere given in the doses of 300, 500 and 1000 mg/kg. Control groupreceived 0.9% NaCI (saline) solution. All the doses administered orally. resultsshowedthat Lactuca hadpotentanalgesicactivityand Artemisia had significantanalgesicand anti-inflammatoryactivity

analgesiceffectsand possible mechanismsof iridoid glycosides from Lamiophlomis rotata (Benth.) Kudo in rats with spared nerveinjury

Ethnopharmacological relevance: Lamiophlomis rotata (Benth.) Kudo (L. rotata) is a medicalplantthat has been traditionally used for centuries for the treatmentof pain, such as bone and muscle pain, jointpainand dysmenorrhea.
Although iridoid glycosides of L. rotata (IGLR) are the majoractivecomponentsof it according to reports, it still remains poorly understood about the molecular mechanismsunderlying analgesiceffectsof IGLR. The aim of the present study was to investigate the analgesiceffectof IGLR on a spared nerveinjury(SNI) model of neuropathicpain.

Materials and methods: The SNI model in rats was established by complete transection of the common peroneal and tibial distal branches of the sciaticnerve, leaving the sural branch intact. Then SNI rats were treatedwith IGLR for 14 days, using normal saline as the negative control. The paw withdrawalmechanical threshold (PMWT) in response to mechanical stimulation was measured by von Frey filaments on day 1 before operation and on days 1, 3, 5, 7, 9, 11, 13 and 14 after operation, respectively. After 14 days, the levels of nitric oxide (NO), nitric oxide synthase (NOS), tumor necrosis factor-a (TNF-a), interleukin-1ß (IL-1ß), interleukin-10 (IL-10) and cyclic guanosine monophosphate (cGMP) in the spinal dorsal horn were measured by the corresponding kits, mRNA expressionof inducible NOS (iNOS) and protein kinase G type I (PKGI) of spinal cord were analyzed by reverse-transcription polymerase chain reaction(RT-PCR). The expressionof N-methyl-D-aspartate receptor(NMDAR) and protein kinase C (PKC?) of the spinal dorsal horn was performed by Western blot. Before all the experiments, motor coordination performance and locomotor activityhad been tested.

Results:Our resultsshowedthat remarkable mechanical allodynia was observedon day 1 after operation in the SNI model, which was accompanied by a decreasein PMWT. treatmentwith IGLR (200, 400, 800 mg/kg) significantlyalleviatedSNI-inducedmechanical allodynia, markedly decreasedthe levels of NO, NOS, TNF-a, IL-1ß and cGMP, and increased the level of IL-10. Meanwhile, IGLR (200, 400, 800 mg/kg) also inhibitedthe protein expressionof NMDAR, PKC? and the mRNA expressionof iNOS and PKG? in the spinal cord. In addition, gavage with the IGLR aqueous extract(800 mg/kg) did not signifiantly alter motor coordination or locomotor activity.

Conclusion:These resultsindicated IGLR could produce an anti-neuropathicpaineffectthat might partly be related to the inhibitionof the NO/cGMP/PKG and NMDAR/PKC pathwaysand the level of TNF-a, IL-1ß as well as to the increaseof the level of IL-10 in spinal cord.

antinociceptiveand anti-inflammatoryactivitiesof iridoid glycosides extractof Lamiophlomis rotata (Benth.) Kudo

Lamiophlomis rotata (Benth.) Kudo is a perennial herb(Labiatae) used as the Tibetan traditional medicinewith the effectsof alleviatingpain, detumescence, hemostasis, promotingblood circulation to remove blood stasis and reinforcing marrow. In this study, we investigated the antinociceptiveand anti-inflammatoryactivitiesof iridoid glycosides extractof L. rotata (IGLR) in mice. Our resultsshowedthat the iridoid glycosides extractcould decreaseacetic-acid-inducedwrithings times and formalin-inducedlickings times, inhibitcarrageenan-inducedhind paw edemaand xylene-inducedear swelling, and suppress peritoneal capillary permeability and leukocyte infiltration also inducedby acetic acid in mice.

All of these resultssuggested that the iridoid glycosides extractpossessesthe significantantinociceptiveand anti-inflammatoryactivities.

Shanzhiside methylester, the principle effectiveiridoid glycoside from the analgesicherbLamiophlomis rotata, reduces neuropathicpainby stimulating spinal microglial ß-endorphinexpression

Lamiophlomis rotata (L. rotata, Duyiwei) is an orallyavailable Tibetan analgesicherbwidely prescribed in China. Shanzhiside methylester (SM) is a principle effectiveiridoid glycoside of L. rotata and serves as a small molecule glucagon-like peptide-1 (GLP-1) receptoragonist. This study aims to evaluate the signal mechanismsunderlying SM anti-allodynia, determine the ability of SM to induce anti-allodynic tolerance, and illustrate the interactionsbetween SM and morphine, or SM and ß-endorphin, in anti-allodynia and anti-allodynic tolerance. Intrathecal SM exerteddose-dependent and long-lasting (>4 h) anti-allodynic effectsin spinal nerveinjury-inducedneuropathicrats, with a maximal inhibitionof 49% and a projected ED50 of 40.4 µg. SM and the peptidic GLP-1 receptoragonist exenatide treatments over 7 days did not induce self-tolerance to anti-allodynia or cross-tolerance to morphineor ß-endorphin.

In contrast, morphineand ß-endorphininducedself-tolerance and cross-tolerance to SM and exenatide. In the spinal dorsal horn and primary microglia, SM significantlyevoked ß-endorphinexpression, which was completely preventedby the microglial inhibitorminocycline and p38 mitogen-activated protein kinase (MAPK) inhibitorSB203580. SM anti-allodynia was totally inhibitedby the GLP-1 receptorantagonistexendin(9–39), minocycline, ß-endorphinantiserum, µ-opioidreceptorantagonistCTAP, and SB203580. SM and exenatide specifically activated spinal p38 MAPK phosphorylation.

These resultsindicate that SM reduces neuropathicpainby activating spinal GLP-1 receptorsand subsequently stimulating microglial ß-endorphinexpressionvia the p38 MAPK signaling. Stimulation of the endogenous ß-endorphinexpressionmay be a noveland effectivestrategy for the discovery and development of analgesicsfor the long-term treatmentof chronicpain.

anti-inflammatoryAND analgesicactivitiesOF leafextractsOF LANDOLPHIA OWARIENSIS

The aqueous, methanol and chloroform extractsof Landolphia owariensis leaves(AELO, MELO & CELO respectively) wainvestigated for anti-inflammatoryand analgesicactivities. All the extracts(100mg/kg each) were foundto significantly(P<0.05inhibitpaw edemainducedby carrageenan in rats and the nociceptioninducedby Tail immersion in hot water (50.0 ± 1.00C) andacetic acid. The methanol extractproducedthe highest paw edemainhibitionwhile in thermally inducednociceptionboth the MELOand CELO show high and comparable analgesicactivitywith acetylsalicylic acid (150mg/kg).

However in chemically inducedpain (acetic acid) MELO producedthe highest and comparable analgesicactivityto acetylsalicylic acid (150mg/kg). We thereforeconclude, that apart from the folklore usesof L. Owariensis leavesas antimalarial agents, the various extractsof the plantalsopossessanti-inflammatoryand analgesicactivities. phytochemicalanalysis showedthat the methanollic extractof L. owerensiscontain some secondary metabolites namely: alkaloidsand some polyphenoliccompounds. Also, this extractexhibitssomeanti-oxidativeactivities

analgesicactivityof the aqueous root extractLecaniodiscus cup anioides

Lecaniodiscus cupanioides is a medicinalplantthat is widely used in folkmedicinein West Africa. In Nigeria, the aqueous root extractof Lecaniodiscus cupanioides (LC) is reportedto be effectiveagainstvarious ailments, including inflammatoryconditions and hepatomegaly. Moreover, there are claims by herbalmedicalpractitioners in Nigeria that LC is useful againstacuteand chronicpain, and that it is safe. This study reports the analgesicactionof LC. The analgesiceffectof LC (100 Š 400mg/kg, p.o.) was investigated in rodents using various painmodels such as hot plate, formalin-inducedpain, tail immersion, tail clip and writhingtestsin mice, as well as tail flick test in rats.

The resultsshowedthat LC produceda significant(P<0.05) prolongation of the reactiontimes in the hot-plate, tail immersion, tail flick and tail clip testsand significantlyand dose-dependently producedan increased painthreshold in both the first and second phases of the formalin paintest. In the writhingtest, LC significantlyinhibitedwrithingfrequency. In all these models, with exception of tail clip and the first phase of formalin-inducedpaintests, LC (400mg/kg) producedeffectscomparable (P<0.05, t-test) to the standard reference drugs, aspirin or morphine.

The resultsindicate that LC has a potentanalgesicaction, mediatedcentrally and peripherally, justifying its use in the management of painin traditional African medicine.

antioxidanteffectsand anti-aging characteristics of Leonurus japonicus H. ethanol extracts

Leonurus japonicus H. is a biennial wild plantthat grows naturally in Asian countries such as Korea, China and Japan and belongs to Labiatae and has been used in lowering blood pressure, promotingurination, as a pain-killer, sedation and in promotingmenstruation. In this study, Leonuri herba’s antioxidantfunction, improvementwere investigated. L. japonicus H. extractwas fractioned into Hexane, Ethyl Acetate, Water, H2O, 30% EtOH, 60% EtOH and 100% EtOH. The investigator carried out an experiment of confirming the capability of superoxide erasure by using the DPPH technique of antioxidantexperiment and Xanthine oxidase hypoxanthine and measured the activation of antioxidantwith ABTS technique. This Study showedthat the 30% EtOH fractionwas highest in antioxidanteffect. Collagense synthesis was significantlyincreased in the experiment of anti-wrinkle effect. All the L. japonicus H. extractsinhibitedthe generation of H2O2 in a dose dependent manner.

Based on the above study findings, the anti-aging effectof 30% EtOH fractionof L. japonicus H. was mostexcellent. In conclusion, the rutin and adenosine of A.japonicus H. extracthad a strong antioxidantfunction. If it is used in cosmetics, a variety of naturalfunctional cosmetics, such as excellent naturalmoisturizers, antioxidantagentsand anti-aging agent, can be developed.

Leonurus japonicus Houtt.: Ethnopharmacology, phytochemistry and pharmacology of an importanttraditional Chinese medicine

Ethnopharmacological relevance: Leonurus japonicus Houtt. (Labiatae), commonly called Chinese motherwort (), is an herbaceous flowering plantnative to Asia. For thousands of years in China, the aerialpart of Leonurus japonicus has been used to treatmenoxenia, dysmenorrhea, amenorrhea, lochia, edemaof the body, oliguresis, sores, ulcerations and other diseasesin women. Now, Leonurus japonicus is listed in the Pharmacopoeia of the People’s Republic of China. The present paper reviewed the ethnopharmacology, phytochemistry, biological actionsand toxicology of Leonurus japonicus.

Materials and methods: Information on Leonurus japonicus was gathered via the Internet (using Elsevier, ACS, Medline Plus, CNKI, VIP, Web of Science, Google Scholar and Baidu Scholar) and libraries.

Results:Approximately 140 chemical compounds have been isolated from Leonurus japonicus, and the majorcomponentshave been determined to be alkaloids, diterpenes and flavones. Among these activecompounds, the effectsof leonurine and stachydrine have been widely investigated. The primary activecomponentsin Leonurus japonicus possesswide pharmacological actions, such as effectson the uterus as well as cardioprotective, anti-oxidative, neuroprotectiveand anti-cancer activities.

Conclusion:Modern pharmacological studieshave demonstratedthat Leonurus japonicus has marked bioactivities, especially on the uterus and as a cardioprotectiveagent. These activitiesare related to its traditional use and provideprospects for the development of noveldrugs, therapeuticsand healthcare products for women. However, the toxicity of Leonurus japonicus will require further study, and the nomenclature for Leonurus japonicus will require additional clarification.

Leonurus japonicus Houtt. commonly called Chinese motherwort. The aerialpartswas used to treatmenoxenia, dysmenorrheaand some women`s diseasesin China. Now, more than 130 chemical compounds have been isolated, and studiesshow that it possesseswide pharmacological actions

analgesicand anti-inflammatoryeffectsof Ligularia fischeri leavesin experimental animals

Aim of the study : The ethanol extract(LF) of Ligularia fischeri var. spiciformis (leaf) has been evaluated for antinociceptiveand anti-inflammatoryactivitiesin mice.

Materials and Methods : Analgesicand anti-inflammatoryactivitieswere studied by measuring nociceptioninducedby formalin, acetic acid and hot-plate, and inflammationinducedby carrageenan, formalin, and arachidonic acid.

Results :The acutetreatmentof mice with LF at doses of 100 and 200 mg/kg, by oraladministration, produceda significantantinociceptiveeffectin the acetic acid-inducedwrithing, formalin-inducedpainlicking and hot-plate-inducedpain. Also, the LF significantlyinhibitedboth carrageenan- and formalin-inducedinflammationas well as arachidonic acid-inducedear edemain mice.

Conclusion :These inhibitions were statistically significant(P < 0.05). Thus, our investigation suggests a potentialbenefit of Ligularia fischeri in treatingconditions associated with inflammatorypain.

effectand mechanismof senkyunolide I as an anti-migraine compound from Ligusticum chuanxiong

Objective : To evaluate the analgesicand anti-migraine activitiesof senkyunolide I from Ligusticum chuanxiong.

Methods : Mice were orallyadministered various doses of senkyunolide I, and their painlevels were assessed in a hot-plate test and by application of acetic acid. The levels of 5-hydroxytryptamine (5-HT), 5-hydroxytryptophan (5-HTP), 5-hydroxyindoleacetic acid (5-HIAA), norepinephrine (NE) and dopamine(DA) in plasma and brainwere assessed, and the monoamine turnover rates (5-HT/5-HTP, 5-HIAA/5-HT and NE/DA) were also calculated.

Results : Mice given senkyunolide I at 16 and 32 mg/kg had significantlyelevated painthresholds in the hot-plate test, and a dose of 32 mg/kg also reducedthe number of abdominal writhingresponses causedby acetic acid. significantimprovements were observedin the neurotransmitter levels of the drug-treatedrats compared with the saline-administered controls. Compared to the rats with nitroglycerin-inducedmigraines, the levels of nitric oxide in the plasma and whole brainof rats given senkyunolide I were lower.

Conclusion : The present study suggests that senkyunolide I may be an activecomponent of L. chuanxiong, traditionally used to treatmigraine. The mechanismof painreliefin migraine model rats may be through adjusting the levels of monoamine neurotransmitters and their turnover rates, as well as decreasing nitric oxide levels in the blood and brain. Therefore, senkyunolide I may be developed as a potentialtreatmentfor migraine pain.

Comparative analgesiceffectof Ligusticum chuanxiong pieces and its products in mice

The present study was undertaken with the objective of finding out the comparative analgesiceffectof Ligusticum chuanxiong (LC) pieces decoction, LC formula granule decoction, liquored LC pieces decoction and liquored LC formula granule decoction. The analgesiceffectswere analyzed using the hot plate and acetic-inducedwrithingtest in mice, and antidysmenorrheic effectwas observedwith primary dysmenorrheamodel. The resultsshowedthat four kinds of LC decoction had definite effectin delaying incubation period and decreasing the writhingfrequency within 30 min. They also effectivelyrelieveddysmenorrhea. Moreover, liquored LC had better analgesiceffectthan crude LC in four decoctions.

antinociceptiveactivityof Ligusticum porteri preparations and compounds

Context :The rootsand rhizomes of Ligusticum porteri Coulter & Rose (Apiaceae) are widely used in Mexican folkmedicinefor several purposes, including painful complaints.

Objective:The main goal of this work was to demonstratethe analgesicactionin mice of some preparations and majorcompounds from L. porteri.

Materials and methods :The extracts, aqueous (AE) and organic (OE), the essentialoil (EO) and majorcompounds (10–316 mg/kg) from L. porteri were evaluated as potentialantinociceptiveagentsusing the acetic acid-inducedwrithingand hot plate testsin ICR mice.

Results : All preparations tested exhibitedsignificantantinociceptiveeffectin the two animal painmodels selected. AE and EO were more effectivein the writhingtest while OE had a better effectin the hot-plate model. On the other hand, Z-ligustilide (1) provoked an increment in the latency period to the thermal stimuli in the hot-plate test at a dose of 31.6 mg/kg, and a decreasein the number of abdominal writhes at 10 mg/kg. Z-3-butylidenephthalide (2) induceda dose-dependent antinociceptiveactionin the hot-plate assay; this compound was also effectivefor controlling the painprovoked by chemical irritation at the doses of 10 and 31.6 mg/kg. Finally, diligustilide (3) inhibitedthe number of writhingresponses at all doses tested but was inactivein the hot-plate model.

Conclusion : The present investigation providesin vivo evidencesupporting the use of L. porteri to treatpainful conditions in folkmedicine.

Evaluation of antioxidant, analgesicand Antidiarrheal activitiesof Methanolic extractof Litsea monopetala (roxb.) leaves

Antioxidant, analgesicand antidiarrheal activitiesof Litsea monopetala (LM) leavesextractswere investigated in order to assessment of pharmacological activities. In vitro antioxidantproperties, in vivo analgesicand antidiarrheal activitieswere investigated in this study. antioxidantplays a remarkable role to protectdifferent kinds of diseasesof human by inhibiting freeradicals. 1, 1-diphenyl-2- picrylhydrazyl (DPPH) freeradicalscavengingwas considered to evaluate the antioxidantproperty. analgesicand antidiarrheal activitieswere investigated in acetic acid inducedwrithingand castor oil inducedantidiarrheal method by white albino mice, respectively. Methanolic extractof LM leaveshas shown antioxidantactivitywith an IC50 valueof 223.22 µg/ml which was compared to the standard ascorbic acid. This extractof LM at a dose of 500 mg/kg showedstatistically significantly(p<0.001) and produced68.75% writhinginhibitionof mice while standard diclofenac sodium drug has shown 76.25% inhibition. LM also produceda significant(P<0.01) reductionin the frequency of diarrhea producedby castor oil in mice compared with Loperamide (50 mg/kg) standard.

This study clearly supports the medicinalvalueof LM`s leaves. However, further study is required to find out the activecomponentswhich are responsible for these activities.

analgesicand anti-inflammatoryactivitiesof methanolic extractof Mallotus repandus stemin animal models

The aim of our current study is to investigate the analgesicand anti-inflammatorypotentials of methanolic extractof Mallotus repandus stem(MSM) using different in vivo assay models. analgesicand anti-inflammatoryactivitieswere evaluated using acetic acid inducedwrithingtest, tail immersion method, hot-plate test, formalin inducedhind paw licking, xylene inducedear edema, carrageenan-inducedpaw edemaand cotton pellet inducedgranuloma in animal model at doses of 500, 1000 and 2000 mg/kg body weight. MSM showedsignificant(p < 0.05) analgesicactivitiesin the acetic acid-inducedwrithingtestsin mice. In the tail immersion and hot-plate test, MSM significantlyprolonged the latency period (p < 0.05). significant(p < 0.05) formalin inducedpaw licking inhibitionwas observedat different doses and the highest 74.47% inhibitionwas observedat 2000 mg/kg.

Besides, MSM showedsignificant(p < 0.05) anti-inflammatoryresponses in carrageenan inducedpaw edema, xylene inducedear edemaand cotton pellet inducedgranuloma methods. These findingssuggest that the plantmay be a potentialsource for the development of new analgesicand anti-inflammatoryagent.

A Mangifera indica L. extractCould Be Used to treatneuropathicpainand Implication of Mangiferin

It has been accepted that neuroinflammation, oxidativestressand glial activation are involved in the central sensitization underlying neuropathicpain. Vimang is an aqueous extractof Mangifera indica L. traditionally used in Cuba for its analgesic, anti-inflammatory, antioxidantand immunomodulatory properties. Several formulations are available, and also for mangiferin, its majorcomponent. Preclinical studiesdemonstratedthat these products preventedtumor necrosis factor a -inducedI?B degradation and the binding of nuclear factor ?B to DNA, which induces the transcription of genes implicated in the expressionof some mediators and enzymes involved in inflammation, pain, oxidativestressand synaptic plasticity.

In this paper we propose its potentialutility in the neuropathicpaintreatment. This hypothesis is supported in the cumulus of preclinical and clinical evidencearound the extractand mangiferin, its majorcomponent, and speculates about the possible mechanismof actionaccording to recent advances in the physiopathology of neuropathicpain.

analgesicbisbenzylisoquinoline alkaloidsfrom the rhizoma of Menispermum dauricum DC

Fifteen new bisbenzylisoquinoline alkaloids(1–15) were isolated from the rhizome of Menispermum dauricum DC. Compounds 1–9were new N-oxides of dauricine-type alkaloids. Compounds 10–14were rare tail-to-tail quaternary alkaloids. Their structures were characterized by comprehensive analysis of spectroscopic data, and absolute configurations were established from electronic circular dichroism (ECD) data and ECD calculations. Compounds were assayed on analgesic-related G-protein coupled receptors(GPCRs) including dopamineD1 and D2 receptors, opioidMu receptorand muscarinic M3 receptor. Compound 1showedhigh affinity and selective antagonistic activityon the M3 receptorwith an IC₅₀ valueof 2.2 ± 0.5 µM; compound 15exhibitedthe highest antagonistic affinity among the evaluated compounds on Mu (IC₅₀ = 1.1 ± 0.6 µM) and it also acted as a D1 receptorantagonist(IC₅₀ = 8.8 ± 2.9 µM).

These findingsexpanded the existing library of bisbenzylisoquinoline alkaloidsand providednew structures for the related future drug design and synthesis.

Mentha spicata as naturalanalgesiafor treatmentof painin osteoarthritispatients

Osteoarthritis, as the majorcause of chronicmusculoskeletal pain, impacts people aged 45 and above. The first line analgesictreatments have reportedminimal short term effects. The use of essentialoils as painkiller has increased, recently. Mentha spicata, or spearmint essentialoil is famous due to its anti-flatulence effects, but one less known biological activityof spearmint is its analgesicactivity. The aim of our study was to confirmthe analgesiceffectsof M. spicata essentialoil. In this review, we evaluated the articles on analgesicactivitiesof M. spicata essentialoil from different relevant databases (PubMed, Science Direct, Wiley, Taylor & Francis, and Springer) withoutlimitation up to April 30, 2016.

Different animal studieshave reportedthe analgesiceffectsof M. spicata essentialoil and its main abundant compounds such as carvone, limonene and menthol, also, the efficacyand safety of spearmint oil in reducingof painseverity were confirmedin osteoarthritispatients. In spite of the beneficial effectsof spearmint oil in reducingof pain, other large clinical trials are required to confirmthe efficacyand safety of M. spicata oil.

analgesic, antiepileptic, and behavioralstudy of Mimosa pudica (Linn.) on experimental rodents

Objective: Mimosa pudica (M. pudica) Linn. (family: Mimosaceae) is a traditionally used folkmedicineto treatvarious ailments including convulsion, alopecia, diarrhea, dysentery, insomnia, tumor, wound, snake bite, etc., Here, the study was aimed to evaluate the potentialon antiepileptic, analgesic, and motor activitiesof M. pudica leaveson rodents.

Materials and Methods: In an acutetoxicity study, the extractswere administered in doses of 50-2,000 mg/kg/p.o. and behavioralchanges were observedfor up to 24 h. For a pharmacological study, the ethyl acetate extractof M. pudica (EAMP) leavesin doses of 100 mg/kg/day, 200 mg/kg/day, and 400 mg/kg/day were orallyadministered for consecutive 7 days to animals. The antiepileptic study was evaluated by inducingelectric shock, pentylenetetrazole (PTZ), and isoniazid (INH) in mice, whereas the motor activitytest was performed by using an actophotometer, rotarod test, and tractiontest in mice. The analgesicactivitywas done by hot-plate, tail flick, and acetic acid-inducedwrithingin rats. Statistical analysis was carried out by one-way analysis of variance (ANOVA) followed by Dunnett’s test.

Results:The EAMP showeddose-dependent analgesicactivityby increasingthe reactiontime as compared to the vehicle control. Similarly, the motor performance was improvedin dose-dependent manner as compared to standard. The doses (100 mg/kg/day, 200 mg/kg/day, 400 mg/kg/day) of the extractsignificantly(P < 0.01 and P < 0.001) reducedthe duration of seizures inducedby maximal electro shock (MES) and delayed the onset of tonic-clonic seizures producedby PTZ and INH. All the tested doses significantlypreventedthe latency and duration of convulsion againstseizure inducers as compared to the vehicle controls.

Conclusion:  These resultsrevealedthat the EAMP possessespotentanalgesic, antiepileptic, and motor activitieson animals. This could be an effectivetreatmentoption for various motor or seizure disorders.

Mimosa pudica Linn (Mimisoideae) is a plantused in traditional medicinefor various disorders. The aim of this work was to evaluate the acutetoxicity and antinociceptiveactivityof the aqueous extractof Mimosa pudica in animal models. In the acutetoxicity study, a single dose of aqueous extractof 2000 mg kg-1 body weight p.o. was administered. For 48 h, animals showedno clinical signs and mortality. In the acetic acid-inducedwrithingmodel, the extractat a dose of 200 & 400 mg kg-1 body weight showedsignificant(p<0.001) inhibitionof writhingresponse of 46.24 and 56.0% respectively. In the hot plate test, the extractproduceda significant(p<0.001) increasein the latency in a dose-related manner. This study established the analgesicpropertiesof Mimosa pudica Linn.

EVALUATION OF analgesicAND anti-inflammatorypotentialOF MIMOSA PUDICA LINN

The aim of this work to evaluate the acutetoxicity, analgesicand anti-inflammatoryactivityof Ethanolic extractof Mimosa Pudica Linn. In the acutetoxicity study, the extractswere administered in doses of 5, 50, 300 and 2000 mg/kg p.o. and behavioralchanges were observedafter 24 hrs. In hot plate test the pethidine treatedgroup, Tail flick Diclofenace treatedgroup, and group given ethanolic extractsas 250 mg/kg and 500 mg/kg showedincreasein latency time dose dependent manner. oraladministration of ethanolic extractat a dose of 500 mg/kg showedsignificantlyreductionof writhingresponse inducedby acetic acid as compared the dose given at 250 mg/kg.

mitragynine

naturalProducts for the treatmentof pain: Chemistry and Pharmacology of Salvinorin A, Mitragynine, and Collybolide

Painremains a very pervasive problem throughout medicine. Classical painmanagement is achievedthrough the use of opiates belonging to the mu opioidreceptor(MOR) class, which have significantside effectsthat hinder their utility. Pharmacologists have been trying to develop opioids devoid of side effectssince the isolation of morphinefrom papaver somniferum, more commonly known as opium by Sertürner in 1804. The naturalproducts salvinorin A, mitragynine, and collybolide represent three nonmorphinan naturalproduct-based targets, which are potentselective agonists of opioidreceptors, and emerging next-generation analgesics. In this work, we review the phytochemistry and medicinalchemistry efforts on these templates and their effectson affinity, selectivity, analgesicactions, and a myriad of other opioid-receptor-related behavioraleffects.

Morinda Citrifolia

analgesicand antiinflammatoryactivityof Morinda citrifolia L. (Noni) fruit

M. citrifolia is a tropical plantwith a long tradition of medicinaluse in Polynesia and tropical partsof eastern Asia and Australia. One of its favorite usesis the treatmentof painful inflammatoryconditions, such as arthritis. The analgesicactivityof Noni fruitpuree on mice was investigated using the hot plate test. A 10% solution of freeze concentrated Noni fruitpuree in the drinking water of mice reducedthe painsensitivity comparably to the central analgesicdrug tramadol. This effectwas only partly reversedby the application of the morphineantagonistnaloxone. An alcohol extractof noni fruitpuree also causedan inhibitionof MMP-9 release from human monocytes after stimulation with LPS. This effectwas comparable to hydrocortisone (10^-5 m). The findingssuggest that preparations of noni fruitsare effectivein decreasing painand jointdestruction causedby arthritis.

analgesiceffectOF THE ALCOHOLIC extractFROM THE fruitsOF MORINDA CITRIFOLIA

The alcoholic extractfrom the fruitsof Morinda citrifolia (noni) was evaluated for analgesiceffectin mice using the acetic acid-inducedwrithingtest. The extractwas administered by i.p. injection in doses of 1, 2, 3 and 4 g of dried plantmaterial kg-1 of animal body weight, 15 min before i.p. injection of acetic acid (0.75%). morphinesulfate (1.5 mg kg^-1, i.p.) was used as the reference drug. Control animals received i.p. injections of 0.9% NaCl solution, instead of the extract. In control mice, the number of writhes during the 20 min test period was 43.0 ± 1.4 (mean ± S.E.M., n=6). The extractsproduceda significantdose-dependent inhibitionof acetic acid-inducedabdominal constriction. The percentage inhibitionwas 4.4 ± 4.5, 21.2 ± 11.2, 71.4 ± 5.0, 93.1 ± 1.7 (mean ± S.E.M., n=6) at the doses of 1, 2, 3 and 4 g kg^-1 respectively, compared to control animals. The inhibitoryeffectof the 4 g kg^-1 dose of extractwas similar to that producedby morphinein a dose of 1.5 mg kg-1. The antinoniceptiveeffectin writhingtest was statistically significant(p<0.001) for 15 min until 5 hr of administration. The data obtained suggest that the alcoholic extraction from the fruitsof Morinda citrifolia appears to have analgesiceffect. Further studiesare necessary for the identification of the activeprinciples and more detailed elucidation of its mechanismof actionis required.

antinociceptiveactivityof freeze dried powdered Morinda citrifolia L. fruit

Objective:The main objective of the study was to establish the antinociceptiveactionof freeze dried powdered Noni againstSwiss albino mice with the help of various in vivo analgesicmodels.

Method:Antinociceptiveeffectof powdered freeze Dried Noni at doses 250 and 500mg/kg b.w was established in Swiss albino mice through acetic acid inducedwrithingtest, radiant heat model, tail immersion model and formalin inducedpainmodel. Diclofenac (10mg/kg) and Pethidine (10mg/kg) were taken as reference for peripheral and central action. Naloxone (2mg/kg) was used to confirmthe central actionof Noni.

Result:It was foundthat the oraladministration of Noni causessignificant(p<0.01) reductionin writhes with Diclofenac as standard. significant(p<0.01) and dose dependent increasein the reactiontime in radiant heat and tail immersion model revealedthe central antinociceptiveeffectof Noni. In Formalin inducedpainmodel, Noni (500mg/kg) showedsignificantinhibitionof paw biting and licking events in both the phases of pain.  Inhibitionof analgesicactivityon i.p administration of Naloxone in tail flick test of Noni and Pethidine confirmedthe central actionof Noni.

Conclusion:Thus it was revealedthat Noni has significantanalgesicactivityand act through both mechanismscentral as well as peripheral.

analgesicactivityof seedsof Moringa oleifera Lam

Moringa oleifera Lam. Seed has been documented to possesantimicrobial and water purifying activitiesand also used in the treatmentof gout, eye infections and in arthritis. Th e alcoholic extractof leavesof Moringa oleifera Lam. were reportedto have analgesicactivitybut seed still not reported. Th e eff ect of alcoholic extractand its various fractionsas Petroleum ether, Ethyl acetate, Diethyl ether, n-Butanol were tested for qualitative analysis which contain glycosides, flavonoids, tannins, amino acids (alpha-4rhamnoloxy benzyl isothiocynate). Th e extractswere also tested for their analgesicactivitywas carried out by using Hotplate and Tail immersion method.Aspirin (25 mg/kg) was used as a standard.

analgesiceffectof ethanolic leafextractof moringa oleifera on albino mice

Objectives : Moringa oleifera is a highly valuedplantdistributed in many countries of the tropic and subtropics. Moringa oleifera leavesare a potentialsource of phytochemicalingredients claimed to have analgesicproperty. painis an unpleasant sensation, which in many cases represents the only symptom for the diagnosis of several diseases. Therefore analgesicdrugs lacking the side effectas alternative to nonsteroidalanti-inflammatorydrugs (NSAIDs) and opiates are in demand by the society. The present study is undertaken to evaluate the analgesicactivityof Moringa oleifera using acetic acid inducedwrithingtest and Eddy’s hot plate test.

Materials and Methods : It is a randomized control study. The present study was done using two experimental models. The albino mice were divided into six groups, each group consisting of 6 mice. A total of 36 mice were used in each of the two experimental models. Group I: Control (normal saline given orallyat 2 ml/kg body weight); Group II: Standard (diclofenac 10 mg/kg i.p/ morphine1 mg/kg i.p); Group III, IV, V, VI (ethanolic extractof Moringa oleifera (EMO) 50, 100, 200, 400 mg/kg, respectively). The EMO leaveswere administered at 50, 100, 200, 400 mg/kg doses orally1 hour before the experiments. For peripheral analgesiceffect, acetic acid inducedwrithingtest was used. The central analgesiceffectwas screened using Eddy’s hot plate method. The standard drug used in acetic acid inducedwrithingtest was diclofenac and in Eddy’s hot plate test was morphine.

Results : The EMO leafshowedsignificant(P < 0.01) analgesicactivityat 100, 200, 400 mg/kg in the acetic acid inducedwrithingtest showing 32.21%, 59.71% and 78.61% inhibitionof writhes, respectivelyin comparison with the control. In the Eddy’s hot plate test EMO at 400 mg/kg showedsignificant(P < 0.01) analgesicactivityfrom 15 min to 90 min with a mean rank ranging from 28.92 to 26.00, second mean rank following morphinein comparison with control. In both the tests, EMO showedsignificant(P < 0.01) analgesicactivityin a dose-dependent manner.

Conclusion : The ethanolic leafextractof Moringa oleifera exhibitedanalgesicactivityin both models showing its both central and peripheral analgesicactions.

Moringa oleifera, a species with potentialanalgesicand anti-inflammatoryactivities

Moringa oleifera has long been used in large demand in folkmedicineto treatpain. The present study was undertaken to examine the antinociceptiveand anti-inflammatoryspectrum of M. oleifera leafextractsdiscriminating the constituents’ nature by using different kind of experimental models in rats. Pharmacological evaluation of a non-polar and/or polar extractsat several doses (30–300 mg/kg, p.o.) was explored through experimental nociceptionusing formalin test, carrageenan-inducedpaw edemaand arthritiswith subcutaneous injection of collagen in rats. Basic morphology characterization was done by scanning electronic microscopy and laser scanning confocal microscopy. Not only polar (from 30 or 100 mg/kg, p.o.) but also non-polar extractproducedsignificantinhibitionof the nociceptivebehavior with majorefficacyin the inflammatoryresponse in different assessed experimental models. This antinociceptiveactivityinvolved constituents of different nature and depended on the intensity of the inducedpainful stimulus. phytochemicalanalysis showedthe presence of kaempferol-3-glucoside in the polar extractand fatty acids like chlorogenic acid, among others, in the non-polar extract.

Data obtained with M. oleifera leafextractsgive evidenceof its potentialfor paintreatment.

analgesiceffectsof methanolic extractsof the leafor root of Moringa oleifera on complete Freund’s adjuvant-inducedarthritisin rats.

Objective : Moringa oleifera (family Moringaceae) has been widely used in African folkmedicine, and researchers have recently revealedits anti-inflammatoryeffectsin human. This study aimed to evaluate the analgesicpropertiesof methanolic extractsof M. oleifera in complete Freund’s adjuvant (CFA)-inducedarthritisin rats.

Methods : Adult male Wistar rats, weighing 200 to 220 g, were used in this study. Adjuvant arthritiswas inducedon day 0 by a single subcutaneous injection of CFA. The prepared extractsfrom both the root and leaf(200, 300 and 400 mg/kg) of M. oleifera were administered intraperitonealy to rats in the treatmentgroups 0, 3 and 6 d after CFA injection and indomethacin (5 mg/kg) was used as a positive control drug. Thermal hyperalgesiaand mechanical allodynia were evaluated for the analgesiceffect0, 3 and 6 d after CFA injection. Combined methanolic root and leafextractsof M. oleifera (200 mg/kg) were also tested for the analgesiceffect.

Results : The potency of the root or leafextractsof M. oleifera (300 and 400 mg/kg) was similar to that of indomethacin, resulted in significantreductions in both thermal hyperalgesiaand mechanical allodynia in rats with CFA-inducedarthritiscompared with the control group after 3 and 6 d, respectively(P<0.01 or P<0.05). Combined root and leafextracts(200 mg/kg) of M. oleifera resulted in a significantreductionin thermal hyperalgesiacompared with the control group after 3 and 6 d, respectively(P<0.01). Prophylactic injections of combined root and leafextractsof M. oleifera (200 mg/kg) resulted in a significantreductionin thermal hyperalgesiacompared with the control group, the root extractsgroup, and the leafextractsgroup after 3 and 6 d, respectively(P<0.01).

Conclusion : The methanolic extractsof the root or leafof M. oleifera are effectivein the reductionof paininducedby CFA in rats. A comparison of single and combination therapies of root and leafextractsalso showeda synergistic effecton painreduction.

anti-inflammatoryand analgesicactivityof stembarkof Moringa Oleifera.

The present study evaluates the anti-inflammatoryand analgesicactivitiesof various extractsof stembarkof Moringa oleifera using various experimental models. The analgesicactivityof stembarkof Moringa oleifera carried out using acetic acid-induced writhingin mice and tail flick test in rats. The anti-inflammatoryactivitywas evaluated using carrageenan-inducedrat paw edemaand cotton pellet-granuloma formation in rats. The effectsof the administration of reference standard (diclofenac) were also evaluated. Two different extracts(Petroleum ether and Methanolic) of Moringa oleifera at the dose level of 100,200 and 400 mg/kg, p.o. were tested. treatmentwith Methanol extract(100, 200, and 400 mg/kg, p.o.) showedsignificant(p<0.01) inhibitionof carrageenan inducedrat paw edema. maximum inhibitionwas observedat 400 mg/kg dose as compared to the control , cotton pellet granuloma formation and acetic acid-inducedwrithing; however, pet ether and methanolic extracts(400 mg/kg, p.o.) were foundto be more effectivein increasinglatency period in tail flick method.

The resultsobtained indicate that Moringa oleifera has analgesicand antiinflammatoryactivities that supports the folkmedicinaluse of the plant.

novelGuaiane Endoperoxides, Nardoguaianone A–D, from Nardostachys chinensis rootsand their antinociceptiveand Antimalarial activities

Four novelguaianoids, nardoguaianone A, B, C and D, were isolated from Nardostachys chinensis roots. The structures were elucidated by spectral means and chemical transformation. antinociceptiveactivitiesof the constituents of N. chinensis, including some of the above novelcompounds, were investigated by the formalin test.  As a result, it was revealedthat nardoguaianone A and D showedactivityat the second phase of paininducedby formalin injection.

Nigella sativa seeds

analgesiceffectof Nigella sativa seedsextracton Experimentally inducedpainin Albino Mice

Objective:To determine the analgesiceffectof ethanolic extractof Nigella sativa seedson experimentally-inducedpainin albino mice.

Study Design:Randomized controlled trial (RCT). Place and Duration of Study: Physiology Department, Services Institute of medicalSciences (SIMS), Lahore, from May to September, 2009.

Methodology:The study was carried out in 90 male albino mice using acetic acid inducedwrithingtest as a chemical model of nociception. The mice were divided in three groups of 30 each. Group A was given normal saline (control); group B was given Nigella sativa seed extractin a dose of 50 mg/kg; and group C received diclofenac sodium, as a reference drug.  Number of writhings in treatedand control groups were compared.

Results:The ethanolic extractof Nigella sativa seedsgiven intraperitoneally causedsignificant(p < 0.05) analgesiceffect on nociceptiveresponse initiated by 0.6% acetic acid; although this analgesiceffectwas less than that producedby diclofenac sodium.

Conclusion:Ethanolic extractof Nigella sativa possessed significantanalgesiceffectin mice.

analgesicand anti-inflammatoryactivitiesof the Methanolic stembarkextractof Nyctanthes arbor-tristis Linn.

Stembarkof Nyctanthes arbor-tristis Linn. was extracted in methanol to evaluate their analgesicand anti-inflammatoryactivities. The analgesicactivitywas determined on Wistar albino rats by hot plate method, tail flick assay, and tail immersion method using morphinesulphate as standard drug at a dose of 5 mg/kg of body weight and the resultswere expressedas mean increasein latency after drug administration ± SEM. The anti-inflammatoryactivitywas assessed by Carrageenan-inducedrat paw oedemausing diclofenac sodium as standard drug at a dose of 100 mg/kg of body weight and expressedin terms of mean increasein paw volume ± SEM. stembarkextractwas given at a dose of 250 mg/kg and 500 mg/kg of body weight. Both standard drugs and extractwere administered orallyto the animals. Control received distilled water orally. resultsshowedthat Nyctanthes arbor-tristis Linn. had potentanalgesicand anti-inflammatoryactivities.

STUDY THE analgesicAND sedativeeffectOF Ocimum basilicum ALCOHOLIC extractIN MALE RATS

This study was carried out on male rats to evaluate the analgesicand sedativeeffectof different doses of Alcoholic extractof Ocimum basilicum leaves. The analgesiceffectstudied by using formalin test, 20 male rats divided to a four groups (5 each), first group exposed water orallyonly before injection of formalin, second group exposed orallywith Diclofenac at a dose 0.71mg/kg B.W before injection of formalin, Third and fourth groups orallyincubated with Alcoholic extractof Ocimum basilicum leavesat a dose (50 and 100mg/kg BW) respectively. While the sedativeeffectstudied by using pentobarbitone sleeping time test and open field test, in each test 15 male rats used and divided to a three groups one of them treatedwith distillated water and the other two groups treatedwith Alcoholic extractof Ocimum basilicum leavesat a dose (50 and 100mg/kg BW) respectively. resultsof formalin test showeda significantreductionin the mean valueof nociceptiveresponse in Diclofenac group specially at late phase while, groups treatedwith Alcoholic extractof Ocimum basilicum leavesrevealeda significantreductionin the nociceptiveresponse valueat the both phases (early and late phase) moreover the group treatedwith 100mg/kg showedthe highest attenuation in the mean valueof nociceptiveresponse compared to 50mg/ kg treatedgroup.

Furthermore, the dose 100mg/kg producedthe potentsedativeeffectin pentobarbitone sleeping time test and open field test. These resultspointed to analgesicand sedativeeffectof Ocimum basilicum may duo to its consistence of the activeanalgesicand sedativecompounds and its effectare in a dose dependent manner

antinociceptiveeffectof Volatile Oils from Ocimum basilicum flowerson Adult Zebrafish

The species Ocimum basilicum L., Lamiaceae, is popular for culinary purposes and medicinaluse as a larvicide, repellent, antifungal, and antimicrobial agent. Therefore, the aim of the present study is to evaluate the chemical composition and antinociceptiveeffectof the volatile oil of O. basilicum flowersusing adult zebrafish (Danio rerio) (n = 6/group) treatedorally(20 µl) with volatile oil (0.25, 1.25, or 2.5 mg/ml; 20 µl) or vehicle (0.9% NaCl, 20 µl). The volatile oil of the O. basilicum flowerswas obtained by hydrodistillation and analyzed by GC–MS, and the antinociceptiveactionis evaluated by different stimuli using motor parameters. The analysis of the chemical profile identified fourteen componentswith linalool (1) as a majorchemical constituent (56.37%). The oraladministration of volatile oil did not show any acutetoxicity or behavior effectsin all tested doses. The volatile oil has a pharmacological potentialfor the treatmentof acutepainby modulation of opioidsystem, N-methyld-aspartate receptors(glutamatergic receptor), and the transient receptorpotentialvanilloid subtype 1 and acid-sensing ion channels.

Together, these data providesupport for analgesicpropertiesof the volatile oil and contribute to suggest that the adult zebrafish model presents the cheapest, cost-effectivepharmacological alternative for the discovery of novelanalgesics.

Onosma bracteatum wall: A potentanalgesicagent

Background:This study was aimed to find out the central and peripheral analgesicactivityof hydro methanolic extractof aerialpartsof Onosma bracteatum.

Material and methods:The central and peripheral analgesicactivityis evaluated by tail flick test and acetic acid inducedwrithingtest at the doses of 50, 100, 250 and 500mg/kg body weight respectivelyin animal models.

Results: The resultsobtained from Tail flick test revealedthat O. bracteatum possessespotentanalgesiceffectsby inducingsignificantincreasein latency period in dose dependent manner at all doses at 1, 2 and 3 hours post feeding respectively. The maximumeffectwas observedat a dose of 500mg/kg i.e. 258.9% (p<0.05) at 3hrs post feeding. Diclofenac sodium (5mg/kg body weight) run as standard also increased the latency period continuously and highest activitywas noted at 3hr i.e. 284.5% (p<0.05). Acetic acid inducedwrithingtest also showedsignificantactivityin a similar manner by O. bracteatum i.e 54% (p<0.05) at 500mg/kg while standard drug Diclofenic sodium (5mg/kg body weight) showed45.9% (p<0.05) activity.

Conclusion: It is concluded that O. bracteatum possessessignificantcentral and peripheral analgesicactivityin animal model.

Preliminary studiesof analgesicand anti-inflammatorypropertiesof Opuntia dillenii aqueous extract

Opuntia dillenii (Ker-Gawl) Haw is a cactus that belongs to the family Opuntiae. Lyophilized aqueous extractof the fruitsof the plant, used in Canarian traditional medicinefor gastrointestinal and bronchial troubles, was evaluated for analgesicand anti-inflammatorypropertiesin rats and mice. The Opuntia dillenii extract(100–400 mg/kg, i.p.) inhibited, in a dose-related manner, carrageenan-inducedpaw edemain rats. A dose-dependent actionwas obtained againstchemical (writhingtest) and thermic (hot plate test) stimuli, respectively, with doses of 50 and 100 mg/kg.

analgesicpotentialof Opuntia dillenii and its Compounds Opuntiol and Opuntioside againstpainModels in Mice.

Opuntia dillenii (Nagphana) traditionally used againstinflammationand also possessanalgesiceffect. Thus in the present study analgesicpropertiesof O. dillenii cladode methanol extract, its fractionsobtained via vacuum liquid chromatography along with isolated a-pyrones, opuntiol and its glucoside, opuntioside were analyzed. The acetic acid-inducedwrithes were reducedby O. dillenii test agentswith opuntioside being mosteffective(IC₅₀ 26 ± 0.9 mg/kg) and equipotentto diclofenac and ß-sitosterol. Consistently, it also elicited mostpotenteffect(IC₅₀: 28 ± 1.1 and 24 ± 1.2 mg/kg) during early and late phases of formalin-inducedpaw licking, producing effectsimilar to diclofenac and indomethacin. It was also mosteffectivein hot plate test. Naloxone (opioidantagonist) reversedthe analgesiceffectsof extractand fractionsbut failed to antagonize the opuntiol and opuntioside analgesiceffects.

In conclusion, edible O. dillenii extract, its fractions, opuntiol and opuntioside reducedperipheral and centrally mediatedpainvia opioiddependent and independent systems. Among them opuntioside emerged as mosteffectiveanalgesicpossibly due to the presence of glucose moiety at position 7 of its a-pyrone ring. This is the first report of opuntiol and opuntioside analgesiceffectwhich may serve as lead compounds in designing of new analgesics.

analgesicand anti-inflammatoryactionof Opuntia elatior Mill fruits

Background: Opuntia elatio Mill is a xerophytic plantwith potentially activenutrients. It is traditionally appreciated for its pharmacological properties; however, the scientific information on this plantis insufficient.

Objective: The present study evaluates the antinociceptiveand anti-inflammatoryactionof prickly pear.

Materials and Methods: Writhingand tail-immersion testswere carried out to evaluate analgesicaction, while the carrageenan-inducedpaw edemaand neutrophil adhesion testswere conducted in Albino wistar rats to assess anti-inflammatoryaction.

Results: ED50 valuesof the fruitjuice in writhing, tail immersion, and paw edematest were 0.919, 2.77, and 9.282 ml/kg, respectively. The fruitsof Opuntia producedanalgesicand anti-inflammatoryactionin a dose-dependent manner.

Conclusion: The resultsestablish the folklore use of prickly pear may be due to the presence of betacyanin and/or other phenoliccompounds.

phytochemicalScreening and Evaluation of analgesicactivityof Oroxylum indicum

We aimed to study phytochemicalscreening and analgesicactivityof ethanol extractof Oroxylum indicum. The dried powder of the barks of the plantwas extracted with 95% ethanol and was subjected to various phytochemicalteststo ascertain the principle constituents contained in the extract.

The resultrevealedthe presence of alkaloids, flavonoids, tannins, glycosides in the ethanol extractof Oroxylum indicum. The extractwas screened for analgesicactivityby using hot plate, acetic acid-inducedwrithingand formalin test. The ethanol extractof the plantat two different doses (250 and 500 mg/kg) showedsignificant(P<0.05) analgesiceffectin all test methods (hot plate, acetic acid-inducedwrithingand formalin). The analgesicactivitywas compared with a standard drug (ketorolac at 10 mg/kg). Based on the present findingsand previous literature review it can be concluded that flavonoidsand tanninsmight be responsible for the analgesicactivity. We suggest that ethanol extractof Oroxylum indicum might have potentialchemical constituents that could be used in the future for the development of novelanalgesicagent.

Investigation of the anti-inflammatoryand analgesicactivitiesof Ethanol extractof stembarkof Sonapatha Oroxylum indicum In Vivo

inflammationis all a pervasive phenomenon, which is elicited by the body in response to obnoxious stimuli as a protectivemeasure. However, sustained inflammationleads to several diseasesincluding cancer. Therefore it is necessary to neutralize inflammation. Sonapatha (Oroxylum indicum), a medicinalplant, is traditionally used as a medicinein Ayurveda and other folksystems of medicine. It is commonly used to treatinflammatorydiseasesincluding rheumatoidarthritisand asthma. Despite this fact its anti-inflammatoryand analgesiceffectsare not evaluated scientifically. Therefore, the anti-inflammatoryand analgesicactivitiesof Sonapatha (Oroxylum indicum) were studied in Swiss albino mice by different methods. The hot plate, acetic acid, and tail immersion testswere used to evaluate the analgesicactivitywhereas xylene-inducedear edemaand formalin inducedpaw edematestswere used to study the anti-inflammatoryactivityof Sonapatha.

The administration of mice with 250 and 300 mg/kg b.wt. of O. indicum reducedpainand inflammationindicating that Sonapatha possessesanalgesicand anti-inflammatoryactivities. The maximumanalgesicand anti-inflammatoryactivitieswere observedin mice receiving 300 mg/kg b.wt. of O. indicum ethanol extract. Our study indicates that O. indicum possessesboth anti-inflammatoryand analgesicactivitiesand it may be useful as an anti-inflammatoryagentin the inflammationrelated disorders.

antioxidant, analgesicand anti-inflammatoryactivitiesof barkof Oroxylum indicum Vent: An Endemic medicinalplantof Northeast India

The aim of this study is to examine possible antioxidant, analgesicand anti-inflammatoryactivitiesof the stembarkof Oroxylum indicum, an endemic plantof Northeast India. The hydro-alcoholic extractwas evaluated for their antioxidantactivityby using DPPH scavengingmethod and phenolicand flavanoidcontent was estimated. The analgesicand anti-inflammatoryassays were carried out on adult male Wistar albino rats by hot plate and carrageenan-inducedpaw edemamethod. The content of phenolicand flavanoidcompound in hydroalcoholic extractin terms of gallic acid and quercetin equivalent (GAE) is 52.67 mg/L and 64.63 mg/L respectively. The extractshowedantioxidantactivitywith IC50 valueof 39.82 -g/mL as compared to the ascorbic acid which exhibitedIC50 valueof 26.17 -g/mL. The analgesicactivitywas assayed by hot plate method using diclofenac as a standard drug at a dose of 10 mg/kg body weight and the resultswere expressedas mean increasein latency after drug administration. The anti-inflammatoryactivitywas evaluated by carrageenaninducedrat paw edemamodel using indomethacin standard drug at a dose of 10 mg/kg body weight. The resultswere expressedin terms of mean increasein paw volume – SEM. The extractof the stembarkwas given in doses of 250 and 500 mg/kg body weight.

All the doses were administered per orally. resultsrevealedthat Oroxylum indicum possesesremarkable analgesicand anti-inflammatoryactivities. Further studiesare needed for isolation of activemolecule and establishment of mechanismof action.

Evaluation of analgesicand antipyreticactivitiesof
various leafextractsof Oroxylum indicum (L.) vent

Background:The ethnobotanicalsurvey and traditional information revealedthat the Oroxylum indicum possessesantipyretic, analgesic, anti-inflammatoryand diuretic activities.

Aim: The present study was an attempt to investigate the analgesic& antipyreticactivityof various extractsof Oroxylum indicum leaves. Methods: The analgesicactivityof O. indicum extractswas evaluated on albino mice by tail immersion methods. Whereas antipyreticactivitywas studied on Brewer’s yeast-inducedpyrexia in Wister strain albino rats. All the crude extractsof O. indicum such as petroleum ether, chloroform and ethanol were tested for analgesicand antipyreticactivityat 100 and 200 mg/kg body weight. Aspirin (50mg/kg) and Paracetamol (100 mg/kg) were used as standard drugs for analgesicand antipyreticactivitiesrespectively.

Results: Among the entire extractpet. ether and ethanol extractshows significantactionin a dose of 200 mg/Kg body weight.  Whereas ethanol extractin a dose of 200 mg/Kg body weight exhibitedsignificantantipyreticactivity after 30 and 45 min as compared to standard paracetamol drug. conclusion: These findings demonstratethat O. indicum leaveshave remarkable analgesicand antipyreticactivitieswhen compared with positive control and thus have great potentialas a source for naturalhealth. The data were verified as statistically significantby using one way ANOVA (analysis of variance) at 5 % level of significance (p<0.05)

Taxonomic and phytomedicinalpropertiesof
Oroxylum indicum (L.) Vent: A wonderful gift of nature

This paper is a review on pharmacological studies, phytochemicalanalysis and problems associated with naturalseed germination of Oroxylum indicum (L.) Vent. The different partsof this plantlike leaves, fruits, stembark, seedsand rootsare used in indigenous medicinepreparation againstvarious diseases. Chemical investigation of various partsof this plantresulted in characterization of various bioactiveprinciples. It shows antioxidative, antitumour, antiinflammatory, analgesic, antimicrobial and hepatoprotectiveactivity. Due to significantmedicinalpropertiesand continuous increasingdemand, this planthas been put in endangered category (IUCN)

analgesiceffectof iridoid glycosides from Paederia scandens (LOUR.) MERRILL (Rubiaceae) on spared nerveinjuryrat model of neuropathicpain

Iridoid glycosides of Paederia scandens (IGPS) is a majoractivecomponent isolated from traditional Chinese herbP. scandens (LOUR.) MERRILL (Rubiaceae). The aim of the present study was to investigate the analgesiceffectof IGPS on spared nerveinjury(SNI) model of neuropathicpain. The SNI model in rats was established by complete transection of the common peroneal and tibial distal branches of the sciaticnerve, leaving the sural branch intact. The mechanical withdrawalthreshold (MWT) in response to mechanical stimulation was measured by electronic von Frey filaments on day 1 before operation and on days 1, 3, 5, 7, 10, and 14 after operation, respectively. Nitric oxide synthase (NOS) activityand nitric oxide (NO) production of spinal cord were measured by spectrophotometry and its cyclic guanosine monophosphate (cGMP) content by radioimmunoassay, mRNA expressionof inducible NOS (iNOS) and protein kinase G type I (PKG-I, including PKG ?a and PKG Iß) of spinal cord were analyzed by RT-PCR.

There was a marked mechanical hypersensitivity response observedon day 1 after operation in SNI model, which accompanied with decreasedMWT. treatmentwith IGPS (70, 140, 280 mg/kg) significantlyalleviatedSNI-inducedmechanical hypersensitivity response evidenced by increased MWT; as well as markedly decreasedNOS activity, NO and cGMP levels. At the same time, IGPS (70, 140, 280 mg/kg) could also inhibitmRNA expressionof iNOS, PKG ?a and PKG Iß in the spinal cord.

The resultssuggested that IGPS possessesantinociceptiveeffect, which may be partly related to the inhibitionof NO/cGMP/PKG signaling pathway in the rat SNI model of neuropathicpain.

Anti-nociceptiveactivityof aqueous fractionfrom the MeOH extractsof Paederia scandens in mice

Aim of the study: We examined the effectsof the aqueous fraction(AF) on nociceptionmodels mice inducedby the chemical and the thermal stimuli so as to elucidate the analgesicactivityand providescientific basis for the clinical use of Paederia scandens.

Materials and Methods: The AF of MeOH extractfrom P. scandens was evaluated on anti-nociceptiveactivityin mice using chemical and thermal models of nociception.

Results: Given orally, the aqueous fractionat doses of 200, 400 and 800 mg/kg producedsignificantinhibitions on chemical nociceptioninducedby intraperitoneal acetic acid and subplantar formalin injections and on thermal nociceptionin the tail-flick test and in the hot plate test. More significantinhibitionof nociceptionwas observedat dose of 800 mg/kg of this fraction. In the pentobarbital sodium -inducedsleeping time test and the open-field test, the aqueous fractionneither significantlyenhancedthe pentobarbital sodium -inducedsleeping time nor impaired the motor performance, indicating that the observedanti-nociceptionwas unlikely due to sedation or motor abnormality.

Conclusions: These resultssuggested that the aqueous fractionproducedanti-nociceptionpossibly related to the iridoid glycosides and polysaccharides in this fraction.

antinociceptiveactivityof petroleum ether fractionfrom the MeOH extractsof Paederia scandens in mice

The petroleum ether fractionof MeOH extractfrom Paederia scandens was evaluated on anti-nociceptiveactivityin mice using chemical and thermal models of nociception. Given orally, the petroleum ether fraction(PEF) at doses of 20, 40 and 80 mg/kg producedsignificantinhibitions on chemical nociceptioninducedby intraperitoneal acetic acid and subplantar formalin or capsaicin injections and on thermal nociceptionin the tail-flick test and in the hot plate test. More significantinhibitionof nociceptionwas observedat dose of 80 mg/kg of the petroleum ether fraction. In the pentobarbital sodium-inducedsleeping time test and the open-field test, the petroleum ether fractionneither significantlyenhancedthe pentobarbital sodium-inducedsleeping time nor impaired the motor performance, indicating that the observedanti-nociceptionwas unlikely due to sedation or motor abnormality.

Moreover, the petroleum ether fraction-inducedanti-nociceptionin both capsaicin and formalin testswas insensitive to naloxone, but was significantlyantagonized by glibenclamide. These resultssuggested that the petroleum ether fractionproducedanti-nociceptionpossibly related to glibenclamide-sensitive K+-ATP channels, which merited further studiesregarding the precise site and mechanismof action. The major constituents of the petroleum ether fraction(PEF) determined by GC/MS analysis, are linoleic acid, the sterols and vitamin E. Therefore it can be suggested that they exertsynergetic effectsand are together responsible for the antinociceptiveactivityof the PEF-fraction.

Paeonia lactiflora Pall. root extract

mechanismsinvolved in the therapeuticeffectsof Paeonia lactiflora Pallas in rheumatoidarthritis

Paeonia lactiflora Pallas, also named Chinese Paeony, is a Chinese herb. A decoction of its root has been used to treatpainful or inflammatorydisordersin traditional Chinese medicine. A water/ethanol extractof Radix Paeoniae is known as total glycosides of paeony (TGP), of which paeoniflorin is the majoractivecomponent. Preclinical studiesshow that TGP/paeoniflorin is able to diminish pain, jointswelling, synovial hypertrophy, and the severity of bone erosion and cartilage degradation in experimental arthritis. TGP/paeoniflorin suppresses inflammatoryprocess by reducingthe production of prostaglandin E2, leukotriene B4, nitric oxide, reactiveoxygen species, proinflammatorycytokinesand chemokines. TGP/paeoniflorin also inhibits the proliferation of lymphocytes and fibroblast-like synoviocytes, the formation of new blood vessels, and the production of matrix metalloproteinases.

Clinical data show that TGP is effectiveto relievethe symptoms and signs of rheumatoidarthritiswithoutsignificantadverse effects.  Recently, TGP is widely used to treatrheumatoidarthritisin China.

The analgesiceffectof Paeoniflorin on Neonatal Maternal Separation–inducedVisceral hyperalgesiain Rats

Paeoniflorin (PF) is one of the principle activeingredients of the root of Paeonia lactiflora Pall (family Ranunculaceae), a Chinese herbtraditionally used to relievepain, especially visceral pain. The present study aimed to investigate both the effectof PF on neonatal maternal separation–inducedvisceral hyperalgesiain rats and the mechanismby which such effectis exerted. A dose-dependent analgesiceffectwas producedby PF (45, 90, 180, and 360 mg/kg i.p.). Centrally administered PF (4.5 mg/kg i.c.v) also produceda significantanalgesiceffect. The analgesiceffectof PF (45 mg/kg i.p.) was maximal at 30 minutes after administration. Furthermore, it was foundthat nor-binaltorphimine (nor-BNI, 3 mg/kg i.p.), dl-a-methyltyrosine (a-AMPT, 250 mg/kg i.p.), and yohimbine (3 mg/kg i.p.) could block the analgesiceffectof PF (45 mg/kg i.p.). Time course determination of PF in brainnuclei showedthat the maximal concentration of PF was 30 minutes after intraperitoneal administration of PF (180 mg/kg) in cerebral nuclei, involving the amygdala, hypothalamus, thalamus, and cortex. These data indicate that PF has an analgesiceffecton visceral painin rats with neonatal maternal separation and that this effectmay be mediatedby ?-opioidreceptorsand a2-adrenoceptors in the central nervous system.

This study demonstrates that PF has an analgesiceffecton painin visceral hyperalgesic rats. These resultssuggest that PF might be potentially useful in clinical therapyfor irritable bowel syndrome as a pharmacological agentin alleviatingvisceral pain.

anti-inflammatoryand immunomodulatory effectsof Paeonia lactiflora Pall., a traditional Chinese herbalmedicine

In China, Korea, and Japan, a decoction of the dried root withoutbarkof Paeonia lactiflora Pall. has been used in the treatmentof rheumatoidarthritis, systemic lupus erythematosus, hepatitis, dysmenorrhea, muscle cramping and spasms, and fever for more than 1200 years. A water/ethanol extractof the root is now known as total glucosides of peony (TGP), which contains more than 15 components. Paeoniflorin is the mostabundant ingredientand accounts for the pharmacological effectsobservedwith TGP in both in vitro and in vivo studies. The analgesiceffectof TGP was confirmedin various animal models of pain, which may be mediatedpartly by adenosine A1 receptor. The direct anti-inflammatoryeffectsof TGP were observedin animal models of both acuteand subacuteinflammation, by inhibiting the production of prostaglandin E2, leukotriene B4, and nitric oxide, and by suppressing the increaseof intracellular calcium ion concentration. TGP was also reportedto have protectiveeffectsof cells againstoxidativestress. In vitro, dual effectsof TGP were noted on the proliferation of lymphocytes, differentiation of Th/Ts lymphocytes, and the production of proinflammatorycytokinesand antibodies. In vivo, TGP inhibitedthe delayed-type hypersensitivity in immuno-activated mice, and enhancedthe delayed-type hypersensitivity in immuno-suppressedmice. In adjuvant arthritisrats, paeoniflorin exertedimmunosuppressive effects. The beneficial effectsof TGP in treatingrheumatoidarthritiswere verified by randomized controlled trials. The adverse events of TGP were mainly gastrointestinal tract disturbances, mostlymild diarrhea.

Paeoniae Radix is one of the mostwell-known herbs in China, Korea, and Japan for more than 1200 years. Paeonies are divided into two groups: the tree Peony (also named Paeonia Moutan) and the herbaceous kinds. Paeonia lactiflora Pall. (also named Chinese Peony) is a herbaceous perennial flowering plantin the family Paeoniaceae with fleshy rootsand annual stems. It is about 60–100 cm tall with large compound leaves20–40 cm long. The flower buds are large and round, opening into large flowers8–16 cm diameter, with 5–10 white, pink, or crimson petals and yellow stamens (Figure 1). It is native to east Asia, and is grown on dry open stony slopes, riverbanks and sparse woodland edges.

Evaluation of analgesicactivityof Papaver libanoticum extractin Mice: Involvement of opioids receptors

Papaver libanoticum is an endemic plantto Lebanese region (family Papaveraceae) that has not been investigated before. The present study aimed to explore the analgesicactivityof dried ethanolic extractof Papaver libanoticum (PLE) using tail flick, hot plate, and acetic acid inducedwrithingmodels in mice. The involvement of opioidreceptorsin the analgesicmechanismwas investigated using naloxone antagonism. resultsdemonstratedthat PLE exhibiteda potentdose dependent analgesicactivityin all tested models for analgesia. The analgesiceffectinvolved activation of opioidreceptorsin the central nervous system, where both spinal and supraspinal componentsmight be involved. The time course for analgesiarevealedmaximumactivityafter three hours in both tail flick and hot plate methods, which was prolonged to 24 hours. Metabolites of PLE could be responsible for activation of opioidreceptors. The EC50 of PLE was 79 and 50 mg/kg in tail flick and hot plate tests, respectively. The total coverage of analgesiaby PLE was double that of morphinein both tests. In conclusion, PLE provedto have opioidagonistic activitywith a novelfeature of slow and prolonged effect. The present study could add a potentialtool in the armaments of opioiddrugs as a naturalpotentanalgesicand for treatmentof opioidwithdrawalsyndrome.

oralintake of purple passion fruitpeelextractreduces painand stiffness and improvesphysicalfunction in adult patients with knee osteoarthritis

Knee osteoarthritis(OA) is a common degenerativejointdisorder and a majorcause of painand disability. The hypothesis tested in this study was that the passion fruitpeelextract(PFP), a flavonoid-rich dietary supplement, would reducesymptoms due to knee OA. Thirty-three OA patients were enrolled in a randomized, double-blind, placebo-controlled trial with parallel-group design. Patients received either placebo or PFP pills (150 mg, daily) in a double-blinded fashion for 2 months. The OA clinical symptoms were evaluated monthly with Western Ontario and McMaster Universities (WOMAC) osteoarthritisIndex. In the PFP group, there was a significantimprovementin total WOMAC score and WOMAC subscale score of physicalfunction after 30 days and painafter 60 days. At 60 days, reductions of 18.6%, 18%, 19.6%, and 19.2% in pain, stiffness, physicalfunction, and composite WOMAC score, respectively, were self-reportedin the PFP group. Whereas, in the placebo group, the self-reportedWOMAC scores increased in every category. The resultsof this study show that PFP substantiallyalleviatedosteoarthritissymptoms. This beneficial effectof PFP may be due to its antioxidantand antiinflammatoryproperties.

effecton inflammatory-cytokinesProduction inhibitionand analgesicactivityof Perilla Frutescens extracts

Prostaglandins biosynthesis and nitric oxide production have been implicated in the process of inflammationand osteoarthritis. And nitric oxide (NO) activated the MMPs responsible for PG degradation in articular chondrocytes. Therefore, we have studied the effectson anti-inflammationand analgesicby ethyl acetate fractionfrom 70% ethanol extractof Perilla Frutescens (EPF). EPF inhibitedLPS plus inflammation-cytokines-inducedproteoglycan (PG) degradation, matrix-metalloproteinase (MMP-2,9) expressionin rabbit articular chondrocytes. Also, EPF have inhibitoryeffectson LPS or LPS plus inflammationcytokines-inducednitric oxide (NO) and PGE2 production in mouse macrophage andrabbit articular chondrocytes.

These resultssuggest that EPF decreases PGE2, iNOS, MMPs activityand PG degradation in mouse macrophage and/or rabbit articular chondrocytes. In vivo, EPF was shown to have inhibitoryeffectson acetic acid-inducedpain. The herbalextractwith this profile, may have utility in the treatmentof osteoarthritis.

analgesic, anti-inflammatoryand anti-ulcer propertiesof Thai Perilla frutescence fruitoil in animals

Perilla frutescens fruitoil (PFO) is rich in a-linolenic acid (ALA) and exhibitsbiological activities. We aimed to investigate analgesic, anti-inflammatoryand anti-ulcer activitiesof PFO and PFO-supplemented soybean milk (PFO-SM) in animal models. analgesicactivitywas assessed in acetic acid-inducedwrithingin mice, while anti-inflammatoryactivitywas performed in ethyl phenylpropiolate (EPP)-inducedear edemaand carrageenan-inducedhind paw edemain rats. Anti-ulcer effectswere conducted in water immersion stress, HCl/ethanol and indomethacin-inducedgastric ulcer in rats. Distinctly, PFO, containing 6.96 mg ALA and 2.61 mg LA equivalence/g, did not induce acutetoxicity (LD₅₀ > 10 mL/kg) in mice. PFO (2.5 and 5 mL/kg) and PFO-SM (0.05 mL PFO equivalence/kg) inhibitedincidences of writhing(16.8, 18.0 and 32.3%, respectively) in acetic acid-inducedmice. In addition, topical applications of PFO (0.1 and 1 mL/ear) significantlyinhibitedEPP-inducedear edema(59.3 and 65.7%, respectively) in rats, while PFO-SM slightly inhibitedear edema(25.9%).

However, PFO and PFO-SM did not inhibitcarrageenan-inducedhind paw edemain rats. Indeed, PFO (2.5 and 5 mL/kg) significantlyinhibitedgastric ulcers in rats that inducedby water immersion stress(92.4 and 96.6%, respectively), HCl/ethanol (74.8 and 73.3%, respectively) and indomethacin (68.8 and 88.9%, respectively), while PFO-SM did not. PFO displayed potentanalgesic, anti-inflammatoryand anti-ulcer properties, while PFO-SM exertedonly analgesicproperties. Thus, Thai PFO and its functional drink offer potentialbenefits in treatmentof analgesic, inflammatorydiseasesand gastric ulcer.

Diuretic and analgesiceffectsof the methanol extractof Phoenix sylvestris root.

The analgesicand diuretic activitiesof the methanol extractof Phoenix sylvestris root on Swiss albino mice were observed. The extractshowedsignificant(p<0.001) analgesicactivityby reductionof percent inhibitionof writhinginducedby acetic acid (0.5% v/v) in 20.07% and 32.57% at a dose level of 150 mg/kg and 300-mg/kg body weights respectively.

The methanol extractalso showeddiuretic effectat 1st hour of the study at 300-mg/kg and 2nd and 4th hour of the study at 150-mg/kg-body weight on swiss albino mice. The onset of diuretic effectwas faster at a dose of 300-mg/kg body weights than 150 mg/kg body weight. The obtained resultsmay give a clue for extensive phytochemicalinvestigation of the plantfor the development of herbalmedicine.

Anti-allodynic and anti-oedematogenic propertiesof the extractand lignans from Phyllanthus amarus in models of persistent inflammatoryand neuropathicpain

This study investigated the anti-allodynic and anti-oedematogenic effectsof the hexanic extract, lignan-rich fractionand purified lignans from a plantused in the traditional medicine, Phyllanthus amarus, in the inflammatoryand neuropathicmodels of nociception. The hexanic extractinhibitedthe allodynia and the oedemainducedby the intraplantar injection of complete Freund’s adjuvant (CFA). The inhibitionobservedwas 76±7% (ipsilateral paw), 64±7% (contralateral paw), and 41±2% (oedema). Otherwise, the lignan-rich fractionor the pure lignans did not affect CFA-inducedallodynia. Administered chronically, the lignan fractionreducedCFA-inducedpaw oedema(39±9%). When evaluated in the model of neuropathicpaincausedby partial ligation of sciaticnerve, the hexanic extractinhibitedthe mechanical allodynia (77±7%), with a similar efficacyto the gabapentin (71±10%). The anti-allodynic effectsof hexanic extractof P. amarus seem not to be associated with the impairment of motor co-ordination or with the development of tolerance.

Finally, the treatmentwith hexanic extractinhibitedthe increaseof myeloperoxidase activity, either following intraplantar injection of CFA or after sciaticnerveinjury. It is concluded that, apart from its anti-inflammatoryactions, which are probably linked to the presence of lignans, another as yet unidentified activeprinciple(s) present in the hexanic extractof P. amarus produces pronounced anti-allodynia in two models of inflammatoryand neuropathicpain. Considering that few drugs are currently available for the treatmentof chronicpain, especially of the neuropathictype, the present resultsmay have clinical relevance and open new possibilities for the development of new anti-allodynic drugs.

potentantinociceptiveactivityof a Hydroalcoholic extractof Phyllanthus corcovadensis

This study analyses the analgesiceffectof a hydroalcoholic extract(HE) from Phyllanthus corcovadensis in several models of painin mice. HE (3–60 mg kg-1, i.p.) or (100–500 mg kg-1, p.o.) causeda graded and potentanalgesiceffectagainstthe abdominal constriction response causedby acetic acid and acetylcholine with an ID50 of about 3 and 100 mg kg-1, respectively. In the tail-flick model HE (up to 500 mg kg-1, p.o.) was withouteffect, while morphine(1–10 mg kg-1, s.c.) causeda graded increasein painlatency (ID50, 3 mg kg-1). HE (1–300 mg kg-1) given both intraperitoneally and orallycauseda potentand graded inhibitionof the second phase of formalin-inducedpersistent painin mice with an ID50 of 1 and 80 mg kg-1, respectively. In contrast, morphine(1–5 mg kg-1, s.c.) inhibitedboth phases of formalin-inducedpainwith an ID50 of 2·5 mg kg-1. Indomethacin (1–10 mg kg-1, i.p.) only inhibitedthe second phase of formalin-inducedpainwith an ID50 of about 3 mg kg-1. The analgesiceffectof indomethacin, but not that causedby morphineand HE was accompanied by a graded inhibitionof formalin-inducedmouse paw oedema. In addition, HE up to 1 g kg-1 failed to preventcarrageenan- and dextran-inducedrat hindpaw oedema.

It is concluded that HE exhibitsa potentantinociceptiveprofile, either when given intraperitoneally or orally. The mechanismsthat underly its analgesiceffectare unclear at present, but appear to be unrelated to inhibitionof synthesis of arachidonic acid via cyclo-oxygenase or to activation of opioidreceptors.

analgesiceffectsof Callus Culture extractsfrom Selected Species of Phyllanthus in Mice

Abstract— The aim of this study was to evaluate the analgesiceffectof the methanolic extractfrom callus culture of Phyllanthus tenellus, P. corcovadensis and P. niruri in several models of painin mice. The extracts(medium containing 2,4-dichlorophenoxyacetic acid) of P. corcovadensis, P. niruri and P. tenellus (3–90 mg kg-1, i.p.) causedgraded inhibitionof abdominal constrictions inducedby acetic acid (0·6%), with ID50 (i.e. dose that reducedresponse of control by 50%) valuesof about 30, 19 and >30 mg kg-1, respectively. The extractof callus of Phyllanthus obtained in indole-3-butyric acid and indole-3-acetic acid media (3–90 mg kg-1, i.p.) causeda similar analgesiceffect. In the formalin test, the extractof P. tenellus obtained in indole butyric acid medium (3–100 mg kg-1, i.p.) inhibitedonly the second phase of formalin-inducedpainwith an ID50 valueof about 100 mg kg-1.

Both the indole acetic acid and indole butyric acid methanolic extractsof P. tenellus and P. corcovadensis (10–100 mg kg-1, i.p.) dose-dependently inhibitedboth phases of formalin-inducedpain(ID50 valuesfor the second phase were approx. 100 and 52 mg kg-1, respectively). However, the extractof callus from Phyllanthus failed to affect formalin-inducedpaw oedema, as well as the response to radiant heat in the tail-flick test. In addition, the analgesiceffectof morphine, but not the analgesiceffectscausedby Phyllanthus callus extract, was fully antagonized by naloxone. Preliminary phytochemicalanalysis revealedthe presence of several compounds having no apparent relationship with alkaloidsor flavonoidsbut showing the presence of phenols.

These resultsindicate that, similar to previous reporteddata from the extractof P. corcovadensis, the methanolic extractsof callus culture of P. niruri, P. corcovadensis and P. tenellus exhibitpotentanalgesicpropertiesagainstneurogenicand inflammatorypainthat seem to be unrelated to the activation of opioidmechanisms.

analgesiceffectsof Callus Culture extractsfrom Selected Species of Phyllanthus in Mice

The aim of this study was to evaluate the analgesiceffectof the methanolic extractfrom callus culture of Phyllanthus tenellus, P. corcovadensis and P. niruri in several models of painin mice. The extracts(medium containing 2,4-dichlorophenoxyacetic acid) of P. corcovadensis, P. niruri and P. tenellus (3–90 mg kg-1, i.p.) causedgraded inhibitionof abdominal constrictions inducedby acetic acid (0·6%), with ID50 (i.e. dose that reducedresponse of control by 50%) valuesof about 30, 19 and >30 mg kg-1, respectively. The extractof callus of Phyllanthus obtained in indole-3-butyric acid and indole-3-acetic acid media (3–90 mg kg-1, i.p.) causeda similar analgesiceffect. In the formalin test, the extractof P. tenellus obtained in indole butyric acid medium (3–100 mg kg-1, i.p.) inhibitedonly the second phase of formalin-inducedpainwith an ID50 valueof about 100 mg kg-1. Both the indole acetic acid and indole butyric acid methanolic extractsof P. tenellus and P. corcovadensis (10–100 mg kg-1, i.p.) dose-dependently inhibitedboth phases of formalin-inducedpain(ID50 valuesfor the second phase were approx. 100 and 52 mg kg-1, respectively).

However, the extractof callus from Phyllanthus failed to affect formalin-inducedpaw oedema, as well as the response to radiant heat in the tail-flick test. In addition, the analgesiceffectof morphine, but not the analgesiceffectscausedby Phyllanthus callus extract, was fully antagonized by naloxone. Preliminary phytochemicalanalysis revealedthe presence of several compounds having no apparent relationship with alkaloidsor flavonoidsbut showing the presence of phenols.

These resultsindicate that, similar to previous reporteddata from the extractof P. corcovadensis, the methanolic extractsof callus culture of P. niruri, P. corcovadensis and P. tenellus exhibitpotentanalgesicpropertiesagainstneurogenicand inflammatorypainthat seem to be unrelated to the activation of opioidmechanisms.

analgesiceffectsof Callus Culture extractsfrom Selected Species of Phyllanthus in Mice

Abstract— The aim of this study was to evaluate the analgesiceffectof the methanolic extractfrom callus culture of Phyllanthus tenellus, P. corcovadensis and P. niruri in several models of painin mice. The extracts(medium containing 2,4-dichlorophenoxyacetic acid) of P. corcovadensis, P. niruri and P. tenellus (3–90 mg kg-1, i.p.) causedgraded inhibitionof abdominal constrictions inducedby acetic acid (0·6%), with ID50 (i.e. dose that reducedresponse of control by 50%) valuesof about 30, 19 and >30 mg kg-1, respectively. The extractof callus of Phyllanthus obtained in indole-3-butyric acid and indole-3-acetic acid media (3–90 mg kg-1, i.p.) causeda similar analgesiceffect. In the formalin test, the extractof P. tenellus obtained in indole butyric acid medium (3–100 mg kg-1, i.p.) inhibitedonly the second phase of formalin-inducedpainwith an ID50 valueof about 100 mg kg-1. Both the indole acetic acid and indole butyric acid methanolic extractsof P. tenellus and P. corcovadensis (10–100 mg kg-1, i.p.) dose-dependently inhibitedboth phases of formalin-inducedpain(ID50 valuesfor the second phase were approx. 100 and 52 mg kg-1, respectively).

However, the extractof callus from Phyllanthus failed to affect formalin-inducedpaw oedema, as well as the response to radiant heat in the tail-flick test. In addition, the analgesiceffectof morphine, but not the analgesiceffectscausedby Phyllanthus callus extract, was fully antagonized by naloxone. Preliminary phytochemicalanalysis revealedthe presence of several compounds having no apparent relationship with alkaloidsor flavonoidsbut showing the presence of phenols. These resultsindicate that, similar to previous reporteddata from the extractof P. corcovadensis, the methanolic extractsof callus culture of P. niruri, P. corcovadensis and P. tenellus exhibitpotentanalgesicpropertiesagainstneurogenicand inflammatorypainthat seem to be unrelated to the activation of opioidmechanisms.

Scientific validation of folkmedicinalusesin Bangladesh of Piper betle L. leavesto alleviatepainand lower

The leavesof Piper betle L. (Piperaceae) are widely chewed in Bangladesh as betel quid with or without tobacco. Chewing of leavesof the plantis advised by the folkmedicinalpractitioners of Bangladesh to alleviatepain(particularly toothache) and lowering of blood sugar, as well as aid the digestive process. The objective of this study was to scientifically evaluate the folkmedicinalpractitioner’s claims of the antihyperglycemic and antinociceptivepropertiesof Piper betle leaves. Antihyperglycemic activityevaluation was conducted through oralglucose tolerance testsin glucose-loaded Swiss albino mice, while antinociceptiveactivitytestswere performed in gastric painmodels in Swiss albino mice, where gastric painwas inducedby intraperitoneal administration of acetic acid. In antihyperglycemic activitytests, methanolic extractof leavesdemonstrated dose-dependent and significantlowering of blood sugar in glucose-challenged mice. At extractdoses of 50, 100, 200 and 400 mg per kg body weight, prior oraladministration of the extractreducedblood sugar levels by 31.01, 34.38, 38.88 and 46.74%, respectively, as compared to control animals. A standard antihyperglycemic drug, glibenclamide, when orallyadministered at a dose of 10 mg per kg body weight lowered blood glucose levels by 46.07%. As such, the resultsstronglyindicate that leavesof the plantpossesspotentantihyperglycemic properties.

In antinociceptiveactivitytests, the methanolic extractof the leavessignificantlyand dose-dependently reducedthe number of gastric writhings in gastric pain-inducedmice. At doses of 50, 100, 200 and 400 mg extractper kg body weight, the percent reductions in writhings were, respectively, 47.00, 63.28, 69.40 and 71.48 as compared to control mice. The standard antinociceptivedrug, aspirin, when administered at doses of 200 and 400 mg per kg body weight, reducedthe number of writhings by 51.04 and 67.32%, respectively. The extract, therefore, appears to be more potentthan aspirin in alleviationof pain.

Overall, the resultsvalidate the folkmedicinalusesof the leavesof this plantand suggest that more scientific researches need to be carried out on isolation and identification of the relevant bioactivecomponentspresent within the leavesof this plant.

preventivepotentials of piperlongumine and a Piper longum extractagainststressresponses and pain

Aim

To compare stressresistance increasingand analgesicactivitiesof piperlongumine and a methanolic Piper longum fruitextract(PLE).
Methods

Efficacies of a single and repeated daily oraldoses (1–256 mg/kg/day) of PLE, piperlongumine, and 50 mg/kg/day doxycycline againstfoot shock stresstriggered alteration in body weights and core temperatures, and of their 11 daily doses on antidepressants like activityin tail suspension test and on pentobarbital inducedsedation in male mice were compared. In another experiment, analgesicactivitiesof single and repeated daily 5 mg/kg oraldoses of piperlongumine and PLE in mice hot plate test and in acetic acid inducedwriting testswere compared with those of aspirin and doxycycline.
results

After their single oraldoses no effectsof piperlongumine or PLE or doxycycline were observedin the footshock stressinducedhyperthermia test or in hot plate test. However, significanteffectsof piperlongumine and PLE in both the testswere observedafter their 5 or more daily doses. Both of them also dose dependently suppresseddaily handling and repetitive testing triggered alterations in body weights and core temperatures. Their doxycycline like antidepressant activityin tail suspension test and aspirin like analgesiceffectsin acetic acid writhingtest were observedafter their 11 daily 5 mg/kg oraldose.
conclusion

Piperlongumine is another bioactivesecondary metabolite of P. longum and other plantsof piper species with stressresponse suppressing, analgesic, and anti-inflammatoryactivities. Its bactericidal activitiescan also contribute to its therapeutically interesting bio-activityprofile.

analgesicand anti-inflammatoryactivitiesof Piper nigrum L.

Objective: To evaluate and compare the analgesicand anti-inflammatoryactivityof pure compound, piperine along with hexane and ethanol extractsof Piper nigrum L. fruitin mice and rats.

Methods: The analgesicactivitywas determined by tail immersion method, analgesy-meter, hot plate and acetic acid inducedwrithingtest. While the anti-inflammatoryactivitywas evaluated by carrageenan-inducedpaw inflammationin rats.

Results: Piperine at a dose of 5 mg/kg and ethanol extractat a dose of 15 mg/kg after 120 min and hexane extractat a dose of 10 mg/kg after 60 min exhibitedsignificant(P<0.05) analgesicactivityby tail immersion method, in comparison to ethanol extractat a dose of 10 mg/kg using analgesy-meter in rats. However, with hotplate method, piperine producedsignificant(P<0.05) analgesicactivityat lower doses (5 and 10 mg/kg) after 120 min. A similar analgesicactivitywas noted with hexane extractat 15 mg/kg. However, in writhingtest, ethanol extractsignificantly(P<0.05) stopped the number of writhes at a dose of 15 mg/kg, while piperine at a dose of 10 mg/kg completely terminated the writhes in mice. In the evaluation of anti-inflammatoryeffectusing plethysmometer, piperine at doses of 10 and 15 mg/kg started producing anti-inflammatoryeffectafter 30 min, which lasted till 60 min, whereas hexane and ethanol extractsalso produceda similar activityat a slightly low dose (10 mg/kg) but lasted for 120 min.

Conclusions: It is concluded from the present study that Piper nigrum L possessespotentanalgesicand anti-inflammatoryactivities.

Evaluation of analgesicpropertiesof Piper Nigrum essentialOil: a randomized, double-blind, placebo-controlled study

Objective:essentialoils are complex mixtures of chemical compounds, extracted from a wide range of plants. The volatile fractionof essentialoils is responsible for their characteristic aroma and presents diverse biological propertiesthat have been studied over the years. In Traditional Chinese medicine, Piper nigrum is considered to be pungent and hot. Although its chemical constituents and respective pharmacological propertieshave been described by several authors, the volatile fractionis still underestimated as a therapeuticagent. The aim of this study was to evaluate the analgesicpropertiesof the volatile fractionof Piper nigrum essentialoil, in patients presenting different types of pain.

Methods:Fifty-four patients presenting pain, were included in a randomized, double-blind, placebo-controlled study, over a 9-week period. The patients were randomly divided into two groups, and asked to inhale a vial containing Piper nigrum essentialoil, or a vial containing a placebo (sesame oil), for 15 minutes. A numerical painscale was applied before and after the inhalation.

Results: resultsshoweda statistically significantdecreasein painintensity in the patients that inhaled the black pepper essentialoil, while the placebo group patients showedno significantchange in painintensity.

Conclusion:Although the resultsare preliminary due to the limited sample size and short inhalation time, the volatile fractionof the Piper nigrum essentialshowedpromisingresultsin reducingpain. In the Chinese medicineperspective, these resultssupport the use of black pepper in different types of pain, since it warms the center and disperses cold.

Pepper as analgesicand anti-inflammatoryAlternative and Bio-enhancer agentfor treatmentof pain

Painis considered as an unpleasant distressing feeling in different partsof body in response to different stimuli. The use of opioids, narcotic and non-narcotic drugs is associated with adverse effects; therefore, research on naturalanalgesicshas been the subjects of many investigations. Due to the traditional importance of Piper nigrum in management of pain, the subject of this article was to evaluate the potency of P. nigrum in pain. The electronic sources (PubMed, Science Direct, Wiley, Springer, etc.) were used to prepare the manuscript by the key words of “black pepper”, “Piper nigrum” and “pain”.

The resultsof different animal studiesconfirmedthat among different species of pepper, P. nigrum or P. longum significantlyreducedthe severity of painand their analgesicpotencies were mediatedby piperine, which inducedthe inhibitionof inflammatorycytokinesand prostaglandin E₂ or activation of calcium influx. Although piperine is foundas analgesiccompounds in pepper, but other componentssuch as piperlongumine or essentialoil enhancedtheir analgesiceffects. P. nigrum, P. longum or piperine is one ingredientof analgesicformulates in combination with Zingiber officinale or Curcuma longa in human clinical studies. Therefore, formulate consists of piperine or P. nigrum in combination with analgesicherbs including Z. officinale, curcumin or ASU blend can be the subject of further clinical studies.

Evaluation of the analgesicactivityof ethyl acetate, methanol and aqueous extractsof Pleurotus eous mushroom

Objective:To evaluate the analgesicactivityof the ethyl acetate, methanol and aqueous extracts ofPleurotus eous (P. eous)mushroom.

Methods: The dried fruiting bodies were extracted with ethyl acetate, methanol and water. The analgesiceffectof extractsofP. eouswere investigated at doses250 500and1 000mg/kg body weight, using acetic-acid inducedwrithing, hot-plate, tail immersion and tail-clip tests.

Results:P. eousextractsproducedsignificantreductionin number of writhes inducedby intraperitoneal injection of acetic-acid(P<0.05). Moreover, in hot-plate and tail immersion test, all the three extractssignificantlyraised the painthreshold at different time of observation (0-60min) in comparison with control(P<0.05). In tail-clip test the extracts also causeda significantinhibitionof painat both the doses used(P<0.05).

Conclusions: The resultsof present study suggest that extractsofP. eouspossesspotentanalgesicproperty and could serve as a base for future drugs.

Polygala anatolica Boiss. et Heldr

Polygala anatolica Boiss. et Heldr.:
Is A potentialremedyfor inflammationand pain?

Species of Polygala genus have been used for the treatmentof inflamation and painin Turkish traditional medicine. The aim of the present study is to assess the anti-inflammatoryand analgesicactivitiesof P. anatolica. n-Hexane, ethyl acetate and methanol extractsof the aerialpartsand rootsof P. anatolica were investigated for their anti-inflammatoryand analgesiceffects. The methanol extractsprepared from the aerialpartsand rootsof P. anatolica were foundto be activein carrageenan- and PGE2-inducedpaw edemamodels and in Whittle method. Methanolic extractof the aerialpart inhibitedserotonin-inducedhind paw edema, while the root extractdid not exertinhibitory effectin the same model. In addition, Fr. B and C obtained from the methanol extractof P. anatolica aerialpartsshowedsignificantanti- inflammatoryactivity.

Morover, the analgesiceffectof the methanol extractsprepared from the rootsand aerialpartsand Fr.B and Fr.C were foundto be statistically significantwithoutinducingulceration. The methanol extract obtained from the aerialpartsof the plantand its saponoside and flavonoid fractionsshowedanti-inflammatoryand analgesicactivitiesin the trials.

Evaluation of the anti-inflammatoryand analgesicactivitiesof the Total Saponins extracted from Fermented Polygala japonica Houtt

This study was to investigate the anti-inflammatoryand analgesicactivitiesof the total saponins extracted from fermented Polygala japonica Houtt (FPH) compared with that of unfermented Polygala japonica Houtt (UFPH). The total saponins extracted from FPH and UFPH were evaluated for anti-inflammatoryactivityin xylene-inducedear swellingand acetic acid-inducedvascular permeability models in mice, analgesicactivityin acetic acid-inducedwrithingand hot plate models in mice. The total saponins extracted from FPH had the significantanti-inflammatory(p<0.001) and analgesic(p<0.01) activitieswith the doses of 6 g/kg b.w. in mice.

The resultsof this experimental study thus stronglysupport the potentialsignificantuse of the total saponins extracted from FPH for painand inflammatory.

analgesicand anti-inflammatoryeffectsof ethyl acetate fractionof Polygonum cuspidatum in experimental animals

Polygonum cuspidatum (PC) has been used for the treatmentof arthritisand urinary diseasesin traditional medicine. Despite recent evidencethat PC has anti-oxidant, anti-tumoral, and anti-inflammatoryeffects, analgesicand anti-inflammatoryeffectsof PC have not been elucidated yet in vivo. Thus, in the present study, analgesicand anti-inflammatoryeffectsof ethyl acetate extractof PC (EAPC) were investigated in vivo for the first time. Hot plate test and tail-flick test revealedthat EAPC at 200 mg/kg exertsanalgesiceffect(p < 0.05). In contrast, EAPC did not show significantanalgesiceffectin acetic acid–inducedwrithingtest. Serotonin-inducedpaw edemamodel and Freund’s complete adjuvant (FCA)–inducedadjuvant arthritismodel were used to examine anti-inflammatoryeffectof EAPC in vivo. In serotonin-inducedpaw edemamodel, EAPC suppressedswellinginflammatoryresponse within 12 min after serotonin injection, at both 100- and 200-mg/kg dose (p < 0.05).

Consistently, in FCA-inducedadjuvant arthritismodel, FCA at 200 mg/kg significantlysuppressedFCA-inducedjointswellingwithin 3 days (p < 0.05), whereas FCA at 100 mg/kg showedthe similar resultwithin 5 days (p < 0.05). Furthermore, EAPC effectivelyinhibitedpositive responses of c-reactiveprotein and rheumatoidfactor compared to untreatedcontrol. Taken together, our findingssuggest that EAPC can be a potentcandidate for rheumatoidarthritistreatment.

Anxiolytic effectsof polydatin through the blockade of neuroinflammationin a chronicpainmouse model

Background:Chronicpainis frequently comorbid with anxiety disorder, thereby complicating its treatment. Polydatin, a component from the root of Polygonum cuspidatum, has shown neuro protection in the central nervous system. However, its effectson painand anxiety processing have been rarely investigated. In this study, mice were injected with complete Freund’s adjuvant (CFA) at the hindpaw to induce pain- and anxiety-like behaviors.

Results:treatmentwith polydatin (25 mg/kg) alleviatedthe anxiety-like behaviors but not painperception in these mice. Polydatin treatmentreversedthe upregulation of N-methyl-D-aspartic acid receptorsand GluA1-containing a-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptorsin the amygdala of CFA-injected mice. Additionally, this treatmentreducedthe levels of proinflammatorycytokines, namely, tumor necrosis factor-alpha and interleukin-1ß, in the amygdala. Furthermore, activated nuclear factor kappa-B signaling was blocked in the amygdala from CFA-injected mice. By using docking technology, we foundpotentialstructural binding between polydatin and I?B kinase beta.
Conclusion:This study indicates the anxiolytic effectsof polydatin by suppressing inflammatorycytokinesin the amygdala.

Study on the Anti-nociceptiveand anti-inflammatoryeffectsof The extractof aerialPart and Rhizome of Paris polyphylla var. chinensis

Abstract: The antinociceptiveand anti-inflammatoryeffectsof the extractof aerialpartsand rhizome of Paris polyphylla var. chinensis were evaluated to find activefractions.The hot plate test,thermal radiation paintest and acetic acid-inducedmouse writhingtest were used to assess the anti-nociceptiveeffectand xylene-inducedmouse ear edemawas conducted to assess the anti-inflammatoryeffectof the extract,fractionsand sub-fractions(furostanol saponin,pennogenin saponin and dioscin saponin).

The resultsshowedthat the rhizome extractdisplayed the significantanti-nociceptiveeffects:the extractat the dose of 2.4 g crude material·kg-1 showedsignificantanti-nociceptiveeffectin the hot plate test,while the extractat the doses of both 0.6 and 2.4 g crude material·kg-1 displayed significantanti-nociceptiveeffectin the thermal radiation paintest.The extractat all doses of (0.3,0.6 and 2.4 g crude material·kg-1)displayed significantanti-nociceptiveeffectin a dose-dependent manner in the writhingtest.The extractsignificantlyinhibitedthe mouse ear edemainducedby xylene in a dose-dependent manner.The extractof aerialpartsshowedthe similar anti-nociceptiveand anti-inflammatoryeffectas those of rhizome.The anti-inflammatoryeffectof aerialpartsand rhizome are attributed to the steroidal saponins enriched in the fractionseluted by 50%,70% and 95% ethanol on macroporous resin chromatography.

All sub-fractions(furostanol,pennogenin and dioscin saponin) demonstratedthe potentanti-inflammatoryeffect,and among them,pennogenin saponins have the strongestactivity.The present investigation providedsome evidences for the development of quality evaluation systemconcerning the traditional efficacyof Paridis rhizoma and the comprehensive utilization of the aerialpartsof Paris polyphylla var. chinensis.

Experimental Study on analgesiaand Hemostasis of Paris polyphylla, Scutellaria baicalensis and Their Compatibility.

Objectives:The analgesicand hemostatic effectsof Paris polyphylla, Scutellaria baicalensis, and their compatibility were studied.

Methods: In the experiment on the writhingof mice inducedby acetic acid, 60 Kunming SPF mice were randomly selected, and were randomly divided into 6 groups according to the male-to-female ratio of 1:1, including blank control group, P. polyphylla group, S. baicalensis group, and three P. polyphylla and S. baicalensis compatibility groups(with the ratio of 1:2, 1:1 and 1:2). There were 10 mice in each group. In the experimental groups, the mice were given 1 g/mL Chinese medicineextractaccording to a dose of 20 mL/kg. In the control group, the mice were given 0.9% normal saline in equal volumes. Gavage was performed one time every 24 h and lasted for 14 d. 1 h after the gavage on the 14 th day, they were given 0.5% glacial acetic acid solution via intraperitoneal injection.  In the hot plate experiment, 60 Kunming SPF mice were selected, and the ratio of male to female, grouping, administration and gavage were the same as those of the glacial acetic acid-inducedwrithingexperiment. Gavage was lasted for 14 d. 1 h after the gavage on the 14 th day, the mice were placed on a hot plate apparatus at(55±0.5) ?, and the time of licking hindfoot was measured.  The hemostatic effectwas explored through three experimental methods of tail hemostasis, femoralartery hemostasis and liver hemostasis. 60 Kunming SPF mice were taken in each of the three experiments, and the male-female ratio and grouping were the same as above. The powder was covered on the surface of the wound sites, and the bleeding was observed. The hemostatic time was recorded, and the hemostatic time was recorded as 3 min if it exceeded 3 min.

Results: In the acetic acid-inducedwrithingexperiment, compared with the blank control group, the painof mice in the experimental groups was inhibited. Among them, P. polyphylla group, S. baicalensis group, compatibility 1:2 group, compatibility 1:1 group, and compatibility 2:1 group had significanteffects(P&lt;0.05), and the inhibitionrate of writhingwas 20.43%, 28.32%, 52.30%, 32.79 %, and 39.02%, respectively. The analgesiceffectof the compatibility 1:2 group was the mostobvious.  In the hot plate experiment, compared with the blank control group, the experimental groups had analgesiceffect. Among them, P. polyphylla group, S. baicalensis group, compatibility 1:2 group, compatibility 1:1 group, and compatibility 2:1 group had significanteffects(P&lt;0.05), and the increaserate of painthreshold was 29.17%, 47.83%, 61.54%, and 50.61%, and 53.83%, respectively. The analgesiceffectof the compatibility 2:1 group was the mostsignificant.  In the hemostatic experiment, there was a significantdifference in hemostatic time between the compatibility 1:2 group and the blank control group, P. polyphylla group, and S. baicalensis group (P&lt;0.05). The hemostatic effectof the compatibility 1:2 group was the best.

Conclusions: P. polyphylla, S. baicalensis, and its compatibility had good analgesicand hemostatic effects, and the best compatibility ratio was 1:2.

naturalProducts: Anti-hyperalgesic effectof an Ethanolic extractof Propolis in Mice and Rats

Propolis, or bee glue, which contains a complex mixture of secondary metabolites, has long been used in many countries for the management of several diseases. The purpose of this study was to evaluate, by means of several pharmacological models, the anti-hyperalgesic effectof propolis collected in the south of Brazil.

The abdominal constrictions inducedin mice by intraperitoneal injection of acetic acid (0.6%), kaolin (50 mg kg^-1) or zymosan (40 mg kg^-1) were inhibitedto different extents by an extractof propolis (1–60 mg kg^-1) administered intraperitoneally 30 min earlier; mean ID50 (concentrations resulting in 50% inhibition) valueswere 2.7, 10.8 and 10.7 mg kg^-1, respectively, and maximuminhibitionwas 58 ± 5, 57 ± 10 and 51 ± 5%, respectively. Given orally(25–200 mg kg^-1, 1 h previously) propolis also inhibitedthe abdominal constrictions inducedby acetic acid (maximuminhibition43 ±5%).

When injected intraperitoneally (3–60 mg kg^-1, 30 min previously), propolis attenuatedboth the neurogenic(first phase) and inflammatory(second phase) painresponses and paw oedemacausedby intraplantar injection of formalin (2.5%); maximuminhibitionwas 32 ±5, 43 ±6 and 19 ±2%, respectively. oraladministration of propolis (25–200 mg kg^-1, 1 h previously) inhibitedboth phases and reducedthe oedemaformation associated with the second phase of the formalin test (maximuminhibition22±5, 33 ±6 and 26±3%) and extractof propolis (3–30 mg kg^-1 i.p. or 25–100 mg kg^-1 p.o., respectively30 min and 1 h previously) significantlyinhibitedcapsaicin-inducedpainwith maximuminhibitionof 39±8 and 41 ±8%, respectively.

When assessed in the Randall–Sellito test of pain, the extractof propolis (3–30 mg kg^-1, i.p., 30 min previously) significantlyreversedthe hyperalgesiainducedby intraplantar injection of bradykinin (3 nmol per paw) in rats (P < 0.01). In contrast with morphinethe extractof propolis (. 100 mg kg^-1, 30 min previously) was ineffectivewhen assessed in the tail-flick and hot-plate thermal assays. Naloxone (5 mg kg^-1 i.p.) reversed(P < 0.01) the effectof morphine(5 mg kg^-1 s.c.) by 70 and 94% respectivelyin the first and second phases of the formalin test, but did not interfere with the analgesiceffectof propolis (10 mg kg^-1 i.p., 30 min previously).

These resultsshow that ethanolic extractof propolis, given systemically, has significantanti-hyperalgesic actionwhen assessed in chemical, but not thermal, models of nociceptionin mice and rats. Its analgesicactionseems to be unrelated to release or activation of the opioidsystem.

Pharmacodynamics assessment of ß-carboline from the rootsof Psammosilene tunicoides as analgesiccompound

Ethnopharmacological relevance: The root of Psammosilene tunicoides (W. C. Wu et C. Y. Wu) is a well-known medicinalherbfor the treatmentof pain, hemostasia and rheumatoidarthritisamong Chinese people.

Aim of the study: The present study aimed to investigate the antinociceptiveactivityand mechanismof ß-carboline alkaloids1–4 which were extracted from the rootsof P. tunicoides.

Materials and methods: The analgesiceffectswere evaluated using peripheral and central painmouse models of nociception, including the formalin test and the tail flick test. The levels of glutamic acid (Glu) and nitric oxide (NO) in cerebellar cortexes and spinal cords (L4-6) were determined. The anti-inflammatoryof all compounds were then assessed on RAW264.7 cells.

Results:Our resultsshowedthat compounds 1–4 had significantanalgesiceffectson both phases of formalin test of mice. Furthermore, all compounds showedsuppressive effectson Glu in the brainand NO levels in the braincortex and the spinal cord. Except for compound 1, the others could extend the painthreshold of hot water tail-flick in mice. In addition, compounds 2 and 3 (60 µmol/kg) could decreaseGABAAa1 protein levels in spinal cord. All compounds exhibitedanti-inflammatoryeffectsby inhibiting lipopolysaccharide (LPS)-inducedNO production in RAW264.7 cells with half-maximal inhibitoryconcentration (IC50) 1.1–34.9 µM.

Conclusion:ß-carboline alkaloidsfrom the rootsof P. tunicoides had significantanalgesicactivityby both central and peripheral mechanisms. Our findingssuggested that regulating the release of NO or Glu or GABAa1 are some of the mechanismsof analgesicactivityof ß-carboline alkaloids.

A water extractof leavesand stems of Psychotria sarmentosa has analgesicand antihyperalgesic activityin rats

An unboiled water extract(UBE) of stems and leavesof Psychotria sarmentosa Blume (Family: Rubiaceae) is drunk by some men in Sri Lanka after being physically assaulted, indicating that it may have potentanalgesicand/or anti-inflammatoryactivity. However, these activitiesare not described in either the Sri Lankan Ayurveda Pharmacopoeia or the Deshiya Chikithsa systemof medicinepractised in Sri Lanka. The aim of this study was to investigate whether an UBE of these partsof P. sarmentosa has such activities. Different doses of the U B E (7.5, 15.0 and 22.5 ml/kg) or vehicle were administered orallyto rats. 1 and 3 h later, the analgesicpotentialwas determined using hot plate and tail flick tests. In another set of rats, the highest dose of U B E was orallyadministered, and paw oedemainducedwith 1% car- rageenan. anti-inflammatoryactivity(up to 4 h) and antihy- peralgesic activity(at 1 h) were determined (by the hot plate technique).

All the doses of U B E were well tolerated and the highest had potentanalgesicactivity(in both tests, in terms of reactiontime and % maximumpossible effect) and anti- hyperalgesic activity(measured 1 h post-treatment). The UBE had no anti-inflarmnatory activity. Its analgesicactivitywas comparable to that of indomethacin and was not blocked by naloxone, (opioidreceptorblocker), metochlopramide (dopaminereceptorblocker) or atropine (cholinergic receptor blocker).

We conclude that the antinociceptiveactivityof the U B E was mediatedboth spinally and supraspinally, and the antihyperalgesic activityspinally. Both actionsmay have been mediatedthrough a paracetamol type of action

anti-inflammatoryand analgesiceffectsof ethanol and aqueous extractsof Pterocephalus hookeri (C.B. Clarke) Höeck

Aim of the study: This study evaluates the anti-inflammatoryand analgesicactivitiesof the ethanol and aqueous extractsof a Tibetan herbPterocephalus hookeri (C.B. Clarke) Höeck to provideexperimental evidencefor its traditional use such as cold, flu and rheumatoidarthritis.

Materials and methods: Investigations on the analgesiceffectsof P. hookeri (C.B. Clarke) Höeck were carried out, including hot-plate test and acetic acid-inducedwrithing. The anti-inflammatoryactivitieswere observedby utilizing the following models: carrageenin-inducededemaof the hind paw of rats, cotton pellet-inducedgranuloma formation in rats, acetic acid-inducedpermeability, and xylene-inducedear edemain mice. The effectsof the administration of indomethacin were also studied.

Results:It has been shown that the ethanol and aqueous extractssignificantlyincreased the hot-plate painthreshold and reducedacetic acid-inducedwrithingresponse in mice. The ethanol and aqueous extractsremarkably inhibitedthe increasein vascular permeability inducedby acetic acid and ear edemainducedby xylene. The ethanol extractalso significantlydecreasedthe carrageenin-inducedrat paw edemaperimeter and inhibitedthe increaseof granuloma weight.

Conclusion:The resultsshow that the ethanol and aqueous extractshave both central and peripheral analgesicactivitiesand as anti-inflammatoryeffects, supporting the traditional application of this herbin treatingvarious diseasesassociated with inflammationand pain.

antinociceptiveand anti-inflammatoryactivitiesof a standardizedextractof bis-iridoids from Pterocephalus hookeri

Ethnopharmacological relevance: Pterocephalus hookeri (C.B. Clarke) Höeck, one of the mostpopular Tibetan herbs, has been widely applied in Tibetan medicineprescriptions. Chemical investigations have led to the isolation of many bis-iridoids. However, the pharmacological activitiesof bis-iridoid constituents of this planthave never been reportedbefore.

Aim of the study: This study evaluated the anti-inflammatoryand analgesicactivitiesof afractionof bis-iridoid constituents of P. hookeri (BCPH) in order to provideexperimental evidencefor its traditional use, such as for cold, flu, and rheumatoidarthritis.

Materials and methods: The analgesiceffectsof BCPH were investigated using the hot-plate test and acetic acid-inducedwrithingtest. The anti-inflammatoryactivitieswere observedusing the following models: carrageenin-inducededemaof the hind paw of rats and xylene-inducedear edemain mice. The effectsof dexamethasone administration were also studied.

Results: BCPH significantlyincreased the hot-platepainthreshold and reducedacetic acid-inducedwrithingresponse in mice. Moreover, BCPH remarkably inhibitedxylene-inducedear edemaand reducedthe carrageenin-inducedrat paw edemaperimeter.

Conclusion: The resultsreveal that BCPH has central, peripheral analgesicactivitiesas well as anti-inflammatoryeffects, supporting the traditional application of this herbin treatingvarious diseasesassociated with inflammationand pain.

The anti-arthritic activityof total glycosides from Pterocephalus hookeri, a traditional Tibetan herbalmedicine

Context : Pterocephalus hookeri (C. B. Clarke) Hock., a traditional Tibetan herbalmedicinerich in glycosides, has been used to treatseveral diseasesincluding rheumatoidarthritis.

Objective : To evaluate the anti-arthritic activityof total glycosides from P. hookeri, and its possible mechanismsof action.

Materials and methods:Anti-arthritic activityof total glycosides from P. hookeri (oraladministration for 30 days at 14–56 mg/kg) was evaluated using paw swelling, arthritisscores and histopathological measurement in adjuvant-inducedarthritis(AA) Sprague-Dawley rats. The NF-κB p65 expressionin synovial tissues, and serum superoxide dismutase (SOD) activity, malondialdehyde (MDA) and nitric oxide (NO) levels was measured in AA rats, respectively. Further assessment of anti-inflammatoryand analgesicactivitiesof these glycosides were carried out using inflammationand hyperalgesiamodels inducedby xylene, carrageenan, agar and acetic acid, respectively.

Results:Total glycosides (56 mg/kg) decreasedthe paw swelling(38.0%, p < 0.01), arthritisscores (25.3%, p < 0.01) and synovial inflammationin AA rats. The glycosides significantly(p < 0.05–0.01) attenuatedthe inflammationinducedby xylene, carrageenan, acetic acid and agar, increased the painthreshold in acetic acid-inducedwrithingin mice and mechanical stimuli-inducedhyperalgia in AA rats. The glycosides (14, 28, 56 mg/kg) also suppressedthe NF-κB p65 expression(33.1–78.2%, p < 0.05–0.01), reducedMDA (21.3–35.9%, p < 0.01) and NO (20.3–32.4%, p < 0.05–0.01) levels, respectively, enhancedthe SOD activity(7.8%, p < 0.05) at 56 mg/kg in AA rats.

Conclusion:Our findingsconfirmedthe anti-arthritic property of the total glycosides from P. hookeri, which may be attributed to its inhibitionon NF-κB signalling and oxidativestress.

analgesicand anti-inflammatoryactivitiesof Flower extractsof Punica granatum Linn. (Punicaceae)

Punica granatum has been used for centuries to confer healthbenefits in a number of inflammatorydiseases. Based on its usage in Ayurvedic and Unani medicine, dietary supplements containing pomegranate extractare becoming popular for the treatmentand prevention of arthritisand other inflammatorydiseases. Pet-ether, dichloromethane and methanol fractionsof flower part were chosen for pharmacological screening and analgesicand anti-inflammatoryactivitiesin animal model.

The anti-inflammatoryactivitywas assessed using the carrageenan-inducedrat paw edemamodel. The analgesiceffectwas measured in mice using the acetic acid-inducedwrithingtest. In the acetic acid-inducedwrithingtest in mice, pet-ether, dichloromethane and methanol fractionsat 200 mg/kg doses level showed75.77% (p

naturalanti-inflammatoryagentsfor painrelief

The use of both over-the-counter and prescription nonsteroidalmedicationsis frequently recommended in a typical neurosurgical practice. But persistent long-term use safety concerns must be considered when prescribing these medicationsfor chronicand degenerativepainconditions. This article is a literature review of the biochemical pathwaysof inflammatorypain, the potentially serious side effectsof nonsteroidaldrugs and commonly used and clinically studied naturalalternative anti-inflammatorysupplements.

Although nonsteroidalmedicationscan be effective, herbs and dietary supplements may offer a safer, and often an effective, alternative treatmentfor painrelief, especially for long-term use.

Qianghuo Shengshi decoction exertsanti-inflammatoryand analgesicvia MAPKs/CREB signaling pathway

Ethnopharmacological relevance: Traditional Chinese medicineQianghuo Shengshi decoction (QSD) is widely used in the treatmentof nervous headache, rheumatoidarthritis, sciatica, allergic purpura, and other clinical diseasesin China. However, the underlying mechanismsof its anti-inflammatoryand analgesiceffectshas not been elucidated.

Aim of the study: The aim of this study was to confirmthe anti-inflammatoryand analgesiceffectsand the underlying mechanismof QSD in vivo. In addition, this study was also to isolate and analyze the main activecomponentsof QSD by high performance liquid chromatography (HPLC).

Materials and methods: In this study, the acetic acid writhingtest, hot plate test and ear swellingtest and formalin test were carried out to explore the anti-inflammatoryand analgesiceffectsof QSD. The doses were set to 7.8 g/kg, 15.6 g/kg and 31.2 g/kg body weight. Western blot was utilized to study further possible mechanismsof QSD. Moreover, the HPLC method was used to isolate and identify the componentsin the extraction of QSD.

Results: Twelve characteristic peaks were recognized in the HPLC spectrum, which all were the known compounds. The QSD exhibiteddose-dependent effectsin anti-inflammatoryand analgesicaspects. Compared with model group, the writhingtimes of in groups of different doses of QSD (15.6 g/kg and 31.2 g/kg (oraladministration = p.o.)) were reducedby 33.0% and 45.8% and indicated the QSD showedsignificant(p < 0.05) peripheral analgesiceffect. QSD ((31.2 g/kg), p.o.) showedsignificant(p < 0.05) analgesiceffectin the hot plate test. inhibitionrates of QSD ((15.6 g/kg and 31.2 g/kg), p.o.) in ear swellingtest inducedby p-xylene were 27.5% and 54.6% and demonstratedthe significant(p < 0.05) anti-inflammatoryactivity. QSD ((31.2 g/kg), p.o.) significantly(p < 0.05) reducedtimes of paw licking in formalin test, and its inhibitionrates were 34.3% and 28.0% in Phase I and Phase Ⅱ response, respectively. Western blot resultsshowedthat QSD inhibitedthe phosphorylation of mitogen-activated protein kinase (MAPK) protein and cAMP response element-binding protein (CREB).

Conclusion: These resultsof this study undoubtedly confirmedthat QSD expressedobvious analgesicand anti-inflammatoryactivities. anti-inflammatoryand analgesiceffectsof QSD may be achievedby regulating the MAPKs protein and further regulating the expressionof CREB. In all, QSD may play an anti-inflammatoryand analgesicrole through a variety of activeingredients.

naturalanti-inflammatoryagentsfor painrelief

The use of both over-the-counter and prescription nonsteroidalmedicationsis frequently recommended in a typical neurosurgical practice. But persistent long-term use safety concerns must be considered when prescribing these medicationsfor chronicand degenerativepainconditions. This article is a literature review of the biochemical pathwaysof inflammatorypain, the potentially serious side effectsof nonsteroidaldrugs and commonly used and clinically studied naturalalternative anti-inflammatorysupplements.

Although nonsteroidalmedicationscan be effective, herbs and dietary supplements may offer a safer, and often an effective, alternative treatmentfor painrelief, especially for long-term use.

antinociceptiveactivityof Ricinus communis L. leaves

Objective: To evaluate the antinociceptiveactivityof the methanol extractof Ricinus communis leaves(MRCL).

Methods: Antinociceptiveactivitywas evaluated using acetic acid inducedwrithingtest, formalin inducedpaw licking and tail immersion method in mice at doses of 100, 125 and 150 mg/kg bw.

Results: The resultsindicated that MRCL exhibitedconsiderable antinociceptiveactivityagainstthree classical models of painin mice. Preliminary phytochemicalanalysis suggested the presence of saponin, steroids and alkaloids.

Conclusions: It can be concluded that MRCL possessesantinociceptivepotentialthat may be due to saponin, steroids and alkaloidsin it.

analgesicand anti-inflammatoryeffectsof Rosa damascena Hydroalcoholic extractand its essentialOil in Animal Models

Extractsobtained from the petals of Rosa damascena (Rosaceae) are used in Iranian folkmedicineas remediesfor the treatmentof some inflammatorydiseases. In this study the hydroalcoholic extractand essentialoil of the plantwere investigated for its possible anti-inflammatoryand analgesicactivities. The extractwas administered at the doses (p.o.) of 250, 500 and 1000 mg/kg and the doses of essentialoil were 100, 200 and 400 μL/kg. The acetic acid-inducedwrithingresponse, formalin-inducedpaw licking time in the early and late phases and light tail flick test were used in mice to assess analgesicactivity. For evaluation of anti-inflammatoryeffectcarrageenan-inducedpaw edemaserved as a valid animal model in rats.

The extractsignificantlyattenuatedthe writhingresponses inducedby an intraperitoneal injection of acetic acid and also showedpotentanalgesiceffectin both phases of formalin test but not in light tail flick test. In addition, the higher dose of the extractsignificantly(P < 0.05) reducedcarrageenan-inducedpaw edema. essentialoil of the plantat all administered doses failed to show any analgesicor anti-inflammatoryeffectin above mentioned tests.

These resultsprovidesupport for the use of hydroalcoholic extractof Rosa damascena in relievinginflammatorypain, and insight into the development of new agentsfor treatinginflammatorydiseases.

anti-inflammatory, analgesicand hepatoprotectiveeffectof Semen of Rumex crispus

Rootsof Rumex crispus (Rc) (Polygonaceae) has been used as therapeuticagentsof acuteand chroniccutaneous diseases, cathartics, fever and jaundice in folkmedicines. Recently, seedsof Rc has known as a digestive, an anticancer agentand a remedyof acutehepatitis, among many traditional folkmedicines. So far it isn’t reportedabout pharmacological effectsof Rumecis Semen.

The present study describes the preliminary evaluations of biological activities, anti-inflammatoryactivity(AA, Carrageenan) analgesicactivity(writhingtest), and hepatoprotectiveactivities($\mathrm{CCl4),\; of\; its\; methanol\; extract,\; ethyl\; acetate\; fractionand\; butanol\; fraction.\; Among\; them\; butanol\; fractionshowedthe\; highest\; activityin\; analgesicacivity.}$

The pharmacological effectsof Salvia species on the central nervous system

Salvia is an importantgenus consisting of about 900 species in the family Lamiaceae. Some species of Salvia have been cultivated world wide for use in folkmedicineand for culinary purposes. The dried root of Salvia miltiorrhiza, for example, has been used extensively for the treatmentof coronary and cerebrovascular disease, sleep disorders, hepatitis, hepatocirrhosis, chronicrenal failure, dysmenorrhea, amenorrhea, carbuncles and ulcers. S. officinalis, S. leriifolia, S. haematodes, S. triloba and S. divinorum are other species with importantpharmacological effects. In this review, the pharmacological effectsof Salvia species on the central nervous systemwill be reviewed.

These include sedativeand hypnotic, hallucinogenic, skeletal muscle relaxant, analgesic, memory enhancing, anticonvulsant, neuroprotectiveand antiparkinsonian activity, as well as the inhibitionof ethanol and morphinewithdrawalsyndrome.

The anti-inflammatoryand the antinociceptiveeffectsof Mixed Agrimonia pilosa Ledeb. and Salvia miltiorrhiza Bunge extract

arthritisis a common condition that causespainand inflammationin a joint. Previously, we reportedthat the mixture extract(ME) from Agrimonia pilosa Ledeb. (AP) and Salvia miltiorrhiza Bunge (SM) could ameliorategout arthritis. In the present study, we aimed to investigate the potentialanti-inflammatoryand antinociceptiveeffectsof ME and characterize the mechanism. We compared the anti-inflammatoryand antinociceptiveeffectsof a positive control, Perna canaliculus powder (PC).

The resultsshowedthat one-off and one-week treatmentof ME reducedthe painthreshold in a dose-dependent manner (from 10 to 100 mg/kg) in the mono-iodoacetate (MIA)-inducedosteoarthritis(OA) model. ME also reducedthe plasma TNF-α, IL-6, and CRP levels. In LPS-stimulated RAW 264.7 cells, ME inhibitedthe release of NO, PGE2, LTB4, and IL-6, increased the phosphorylation of PPAR-γ protein, and downregulated TNF-α and MAPKs proteins expressionin a concentration-dependent (from 1 to 100 µg/mL) manner.

Furthermore, ME ameliorated the progression of ear edemain mice. In mostof the experiments, ME-inducedeffectswere almostequal to, or were higher than, PC-inducedeffects. conclusions: The data presented here suggest that ME shows anti-inflammatoryand antinociceptiveactivities, indicating ME may be a potentialtherapeuticfor arthritistreatment.

Pharmacological and molecular docking assessment of cryptotanshinone as natural-derived analgesiccompound

medicinalplantsfrom traditional chinese medicineare used increasingly worldwide for their benefits to healthand quality of life for the relevant clinical symptoms related to pain. Among them, Salvia miltiorrhiza Bunge is traditionally used in asian countries as antioxidant, anticancer, anti-inflammatoryand analgesicagent. In this context, several evidences support the hypothesis that some tanshinones, in particular cryptotanshinone (CRY), extracted from the roots(Danshen) of this plantexhibitanalgesicactions. However, it is surprisingly noted that no pharmacological studieshave been carried out to explore the possible analgesicactionof this compound in terms of modulation of peripheral and/or central pain.

Therefore, in the present study, by using peripheral and central painmodels of nociception, such as tail flick and hot plate test, the analgesiceffectof CRY in mice was evaluated. Successively, by the aim of a computational approach, we have evaluated the interactionmode of this diterpenoid on opioidand cannabinoid system. Finally, CRY was dosed in mice serum by an HPLC method validated according to European medicinesAgency guidelines validation rules.

Here, we report that CRY displayed anti-nociceptiveactivityon both hot plate and tail flick test, with a prominent long-lasting peripheral analgesiceffect. These evidences were indirectly confirmedafter the daily administration of the tanshinone for 7 and 14 days. In addition, the analgesiceffectof CRY was reverted by naloxone and cannabinoid antagonists and amplified by arginine administration. These findingswere finally supported by HPLC and docking studies, that revealeda noteworthy presence of CRY on mice serum 1 h after its intraperitoneal administration and a possible interactionof tested compound on μ and k receptors.

Taken together, these resultsprovidea new line of evidences showing that CRY can produce analgesiaagainstvarious phenotypes of nociceptionwith a mechanismthat seems to be related to an agonistic activityon opioidsystem.

Evaluation of marine brown algae Sargassum ilicifolium extractfor analgesicand anti-inflammatoryactivity

Background: The methanolic extractof Sargassum ilicifolium (Pheophyceae) was used to evaluate its analgesicand anti-inflammatoryactivityin the present study.

Materials and Methods: Analgesicactivitywas tested using Acetic acid writhingmethod and Eddy hot plate method in Male albino mice and Wister rats respectivelyat a dose level of 1, 10, 50, 100mg/kg p.o. At the same dose, its anti-inflammatoryactivitywas also tested using Carrageenan inducedrat paw edemamethod resultAcetic acid writhingtest and Eddy’s hot plate episodes were significantlyand dose dependently reduced. Carrageenan (a standard inflammatoryagent) inducedpaw edemain rats was significantlyreducedafter intraperitonal administration of methanolic extract.

Results: Showeddose dependant significantactivityin comparison with standard and control.

Conclusion: Methanolic extractsof the brown seaweeds Sargassum ilicifolium have potentanalgesicand anti-inflammatoryactivityat moderate doses.

analgesicAnd anti-inflammatorypropertiesOf Aqueous extractFrom leavesOf Solanum torvum (Solanaceae)

Solanum torvum is used in Cameroonian traditional medicinefor the management of painand inflammation. The present work assesses the pain-killing and anti-inflammatorypropertiesof the aqueous extractsof Solanum torvum leaves. Acetic acid- and pressure- inducedpains were reducedby this extractwhile carrageenan-inducedinflammationwas inhibitedat various doses of the extract. The extracttherefore has both analgesicand anti-inflammatoryproperties.

Evaluation Of analgesicpotentialOf Solanum Trilobatum roots

In the present work, the antinociceptiveactionwas assayed in several experimental models in mice: writhing, formalin and hot plate tests. The crude alkaloidfraction(25, 50, 100 mg/kg) and in a dose-dependent manner significantlyreducedthe nociceptionby acetic acid intTaperitoneal injection (P<0.00 I). In the formalin test, the extract(50 and 100 mg/kg) also significantlyreducedthe painful stimulus in both phases of the test (P<0.001). treatmentwith the extract(25, 50, 100 mg/kg) when given i.p. or pentazocine (5 mg/kg, s.c.) produceda significantincreaseof the reactiontime in hot plate test.

These resultshowedthat the alkaloidextractof Solanum trilobatum contains activeanalgesicprinciples acting both centrally and peripherally.

analgesic, anti-inflammatoryand Anti-Biofilm-Forming activityof Potato (Solanum tuberosum L.) peelextract

The utilization of naturalresources, one of which is plants, has been researched as an alternative to synthetic drugs because of their naturalcontent. Potato (Solanum tuberosum L.) peels, the partsof potatoes that are often cut off and discarded, have been reportedto have some phenoliccompounds and flavonoidsin their composition. The extractof potato peelswas investigated for its analgesic, anti-inflammatory, and anti-biofilm-forming properties. A hot plate test was conducted to assess the analgesicactivityin treatmentdoses of 50 mg/kg, 100 mg/kg, and 200 mg/kg with paracetamol as the reference drug and distilled water as the negative control, while carrageenan-inducedpaw edemawas used to assess anti-inflammatoryactivityin treatmentdoses of 100 mg/kg, 200 mg/kg, and 400 mg/kg with diclofenac as the reference drug and distilled water as the negative control. Anti-biofilm-forming activitywas tested by using the crystal violet assay.

The resultsshowedthat, compared with the negative control, treatmentdoses of 100 mg/kg and 200 mg/kg significantly(p < 0.05) reducedpainstimuli, whereas a treatmentdose of 100 mg/kg, 200 mg/kg, and 400 mg/kg significantly(p < 0.05) reducedthe edemavolume increment. However, compared with the positive control, paracetamol and diclofenac were associated with the least painstimulus and the least edemavolume increment, respectively. Potato peelextractagainstS. mutans biofilm formation demonstratedeffectiveness (p < 0.05).

Based on these data, it can be concluded that potato peelextracthas analgesic, anti-inflammatory, and anti-biofilm-forming activities, as demonstratedin this study.

anti-inflammatoryactivityof Some Characteristic Constituents from the Vine stems of Spatholobus suberectus

The dried vine stems of Spatholobus suberectus are commonly used in traditional Chinese medicinefor treatinggynecological and cardiovascular diseases. In this study, five new compounds named spasuberol A (2), homovanillyl-4-oxo-nonanoate (5), spasuberol C (6), spasuberoside A (14), and spasuberoside B (15), together with ten known compounds (1, 3, 4, 7–13), were isolated from the dried vine stems of S. suberectus. Their chemical structures were analyzed using spectroscopic assays. This is the first study interpreting the detailed structural information of 4.

The anti-inflammatoryactivityof these compounds was evaluated by reducingnitric oxide overproduction in RAW264.7 macrophages stimulated by lipopolysaccharide. Compounds 1 and 8–10 showedstrong inhibitoryactivitywith half maximal inhibitoryconcentration (IC50) valuesof 5.69, 16.34, 16.87, and 6.78 μM, respectively, exhibitinghigher activitythan the positive drug l-N6-(1-iminoethyl)-lysine (l-NIL) with an IC50 valueof 19.08 μM. The IC50 valuesof inhibitoryactivityof compounds 2 and 4–6 were 46.26, 40.05, 45.87, and 28.29 μM respectively, which were lower than l-NIL, but better than that of positive drug indomethacin with an IC50 valueof 55.44 μM.

Quantitative real-time polymerase chain reactionanalysis revealedthat assayed compounds with good anti-inflammatoryactivity, such as 1, 6, 9, and 10 at different concentrations, can reducethe messenger RNA (mRNA) expressionof some pro-inflammatorycytokinessuch as tumor necrosis factor α (TNF-α), nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX-2). The anti-inflammatoryactivityand the possible mechanismof the compounds mentioned in this paper were studied preliminarily.

Preliminary studieson antiinflammatoryand analgesicactivitiesof Spilanthes acmella in experimental animal models

To evaluate the antiinflammatoryand analgesicactivitiesof the aqueous extractof Spilanthes acmella (SPA) in experimental animal models.

SPA was evaluated for antiinflammatoryactionby carrageenan-inducedrat paw edema. The analgesicactivitywas tested by acetic acid-inducedwrithingresponse in albino mice and tail flick method in albino rats.

The aqueous extractof SPA in doses of 100, 200 and 400 mg/kg showed52.6, 54.4 and 56.1% inhibitionof paw edemarespectivelyat the end of three hours and the percentage of protection from writhingwas 46.9, 51.0 and 65.6 respectively. In the tail flick model, the aqueous extractof SPA in the above doses increased the painthreshold significantlyafter 30 min, 1, 2 and 4 h of administration. SPA showeddose-dependent actionin all the experimental models.

The present study indicates that SPA has significantantiinflammatoryand analgesicproperties.

analgesiceffectsof Triterpenoid Saponins From Stauntonia chinensis via Selective increasein inhibitorySynaptic Response in Mouse Cortical Neurons

Triterpenoid saponins from Stauntonia chinensis (TSS) are potentialtherapeuticagentsbecause of its analgesicproperties. However, the underlying mechanismsof the anti-nociceptiveactivityof TSS are largely unclear, especially in CNS. The present study confirmedthe analgesiceffectof TSS using four models of acutepainbased on thermal or chemical stimuli. TSS treatmentspecifically impaired the threshold of thermal- and chemical-stimulated acutepain. Naloxone did not block the anti-nociceptiveeffectsof TSS, which showedno participation of the opioidsystem. We investigated the electrical signal in cultured cortical neurons to explore whether TSS treatmentdirectly affected synaptic transmission. TSS treatmentselectively increased spontaneous inhibitorysynaptic release and GABA inducedcharge transfer in mouse cortical neurons.

The effectsof TSS were maintained for at least 8 h in cultured neurons and in injected mice. Taken together, our resultssuggest that the analgesicrole of TSS in cortex occurs via a particular increasein the inhibitorysynaptic response at resting state, which supports TSS as a potentialcandidate for inflammatorypainrelief.

analgesiceffectsof Triterpenoid Saponins From Stauntonia chinensis via Selective increasein inhibitorySynaptic Response in Mouse Cortical Neurons

The aim of this investigation was to study the anti-nociceptiveand anti-inflammatoryactivitiesof Stauntonia chinensis (S. chinensis) and the possible actionmechanismsof effectivefractions. The anti-nociceptiveand antiinflammatoryactivitiesof S. chinensis extracts, including the 60% EtOH extract(YMG), the n-BuOH extract(YMGB) and the aqueous residue (YMGW) of YMG, and the fractionsfrom YMGB (YMGB1~YMGB7) were investigated by using the mouse acetic acid-inducedwrithingtest and the rat formalin test.

The effectof these extractson the PGE2 production was tested as well. In the mouse acetic acid-inducedwrithingtest and the rat formalin test, YMGW and YMGB displayed anti-nociceptiveand anti-inflammatoryactivities, suggesting that they were the activeingredients of YMG. Among the fractionsisolated from YMGB, YMGB1, YMGB3, YMGB4 and YMGB6 were the main activeingredients producing anti-nociceptiveactivityand YMGB3, YMGB5, YMGB6 and YMGB7 were the main activeingredients producing anti-inflammatoryactivity. Additionally, YMGW, YMGB and its separations reducedthe production of PGE2, which might be the mechanismof them producing anti-inflammatoryactivity.

These resultsdemonstratedthe activeingredients of S. chinensis producing anti-nociceptiveand anti-inflammatoryactivities, which is valuableto validate the substance basis of S. chinensis’s pharmacological actions.

Bidesmoside triterpenoid glycosides from Stauntonia chinensis and relationship to anti-inflammation
Ten triterpenoid glycosides, yemuoside YM_26–35 (1–9and 12), were isolated from a traditional Chinese medicineknown as “Ye Mu Gua” (Stauntonia chinensis DC.) along with two known ones, kalopanax saponin C (10) and sieboldianoside A (11). Their structures, as elucidated by spectroscopic analyses and chemical methods, were either penta-saccharidic or hexa-saccharidic bidesmoside triterpenoid glycosides. To help explain the clinical applications of “Ye Mu Gua” for its anti-inflammatoryeffects, the inhibitoryactivityon the release of inflammatorymediators (nitric oxide, TNF-a and IL-6) of 1–12and the related aglycone, hederagenin (13), was evaluated in vitro. It was foundthat compound 13, but not 1–12, exhibitedsignificantinhibitoryactivity.

The abundant triterpenoid glycosides in “Ye Mu Gua” might therefore be transformed into their respective aglycones, and thus inhibitthe release of inflammatoryfactors in vivo. This could then account for the clinical valueof “Ye Mu Gua” as regards anti-inflammatoryeffects. This proposed explanation of how “Ye Mu Gua” may have an effectis similar to the concept of prodrugs for chemical drugs which could be extended to some traditional medicines. That is, the majorcomponentsmight be biologically activenot directly, but via biochemical transformation in vivo. Hence, we propose a “traditional medicine’s prodrug characteristic” concept.

phytochemicalscreening and study of antioxidantand analgesicpotentials of ethanolic extractof Stephania japonica Linn.

The present study was conducted to evaluate the possible phytochemicals present, antioxidantactivityand analgesicpotentialof ethanolic extractof leavesof Stephania japonica (Linn.). For investigating the antioxidantactivity, four complementary test systems, namely 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicalscavenging, reducingpower assay, Fe++ ion chelating ability and total phenoliccontent were used. analgesicactivityof the extractwas evaluated using acetic acid-inducedwrithingmodel of painin mice. In DPPH freeradicalscavengingtest, IC 50 valuefor ethanolic crude extractwas foundmoderate (18.57 ± 0.079 μg/ml) while compared to the IC50 valuesof the reference standards ascorbic acid and BHA (1.93 ± 0.027 and 4.10 ± 0.035 μg/ml), respectively.

In reducingpower assay, the maximum absorbance for ethanolic crude extractwas foundto be 2.013 ± 0.024 at 100 μg/ml, compared to 2.811 ± 0.013 and 2.031 ± 0.019 for standard ascorbic acid and butylated hydroxyanisole (BHA), respectively. The IC 50 valueof the extractas % Fe ++ ion chelating ability was determined as 18.68 ± 0.029, where ethylenediaminetetraacetic acid (EDTA) showed8.87 ± 0.035.

The total phenolicamount was also calculated as moderate in ethanolic crude extract(237.71 ± 0.57 mg/g of gallic acid equivalent). At the dose of 500 mg/kg body weight, the extractshowedsignificantanalgesicpotentialin acetic acid induced writhingin mice, showing 41.47% inhibition(P < 0.001) comparable to that producedby diclofenac Na (45.02%) used as standard drug. These resultsshow that ethanolic extractof leavesof S. japonica (Linn.) has moderate antioxidantand potentanalgesicactivity.

These activitiesincreasewith the increaseof concentrations. The potency of the extractmay be due to the presence of phytochemicals like tannins, flavonoids, phenolics etc.

analgesicand anti-inflammatorypropertiesof brucine and brucine N-oxide extracted from seedsof Strychnos nux-vomica

To further understand the purpose of the traditional processing method of the seedsof Strychnos nux-vomica L. (Loganiaceae) as well as analgesicand anti-inflammatoryactivitiesof brucine and brucine N-oxide extracted from this medicinal plantfrom ScienceDirect’s AI-generated Topic Pages” medicinalplant, various painand inflammatorymodels were employed in the present study to investigate their pharmacological profiles. Both brucine and brucine N-oxide revealedsignificantprotectiveeffectsagainstthermic and chemical stimuli in hot-plate test and writhingtest. However, on different phases they exertedanalgesicactivitiesin formalin test.

Brucine N-oxide showedstrongerinhibitoryeffectthan brucine in carrageenan-inducedrat paw edema, both of them significantlyinhibitedthe release of prostaglandin E₂ in inflammatorytissue, reducedacetic acid-inducedvascular permeability and the content of 6-keto-PGF_1a in Freund’s complete adjuvant (FCA) inducedarthritisrat’s blood plasma. In addition, brucine and brucine N-oxide were shown to reducethe content of 5-hydroxytryptamine (5-HT) in FCA-inducedarthritisrat’s blood plasma, while increasethe content of 5-hydroxytryindole-3-acetic acid (5-HIAA) accordingly.

These resultssuggest that central and peripheral mechanismare involved in the painmodulation and anti-inflammationeffectsof brucine and brucine N-oxide, biochemical mechanismsof brucine and brucine N-oxide are different even though they are similar in chemical structure.

analgesicand anti-inflammatoryactivityand pharmacokinetics of alkaloidsfrom seedsof Strychnos nux-vomica after transdermal administration: effectof changes in alkaloidcomposition

Ethnopharmacological relevance: Strychnos nux-vomica L. (Loganiaceae) is grown extensively in southern Asian countries. The dried seed of this plant, nux vomica, has been clinically used in Chinese folkmedicinefor improvingblood circulation, relievingrheumatic pain, reducingswellingand treatingcancer.

Aim of the study: This study was carried out to investigate the effectof removing moststrychnine from the total alkaloidfraction(TAF) extracted from nux vomica on analgesicand anti-inflammatoryactivityand pharmacokinetics after transdermal administration.

Materials and methods: Most strychnine was removed from TAF and the resulted modified total alkaloidfraction(MTAF) was obtained. The contents of strychnine and brucine in TAF and MTAF were determined. Then the analgesicand anti-inflammatoryactivityof TAF, MTAF, brucine and strychnine dissolved in hydrogel was compared after transdermal administration. Furthermore, in vitro and in vivo transdermal absorption profiles of brucine after administration of TAF, MTAF and brucine dissolved in hydrogel were also compared.
results

Results : In contrast to TAF, moststrychnine was removed from MTAF and the ratio of brucine to strychnine was adjusted from 1:1.8 to 2.7:1. MTAF showedsignificantanalgesicactivityin all the chemical-, thermal- and physical- inducednociceptionmodels, which indicated the presence of both centrally and peripherally mediatedactivities. MTAF also showedsignificantanti-inflammatoryactivityagainstxylene-inducedear edema. But TAF and strychnine demonstratedlittle activityin all those pharmacological tests. Brucine showedto be effectivein acetic acid-inducedwrithingand xylene-inducedear edematest. Brucine in MTAF was absorbed more completely than it alone at the same dosage of brucine after transdermal administration.

Conclusion : The resultsfrom the present study appeared to support the viewpoint that moststrychnine should be removed from TAF to improveanalgesicand anti-inflammatoryactivity. The relatively higher pharmacological activityof MTAF compared to brucine alone is partly due to the enhancedtransdermal absorption of brucine.

phytochemicalstudy, cytotoxic, analgesic, antipyreticand anti-inflammatoryactivitiesof Strychnos nux-vomica

The strychnine tree (Strychnos nux-vomica L.) (S. nux-vomica) belonging to family Loganiaceae has been a very promisingmedicationfor certain disorders. Different chromatographic methods were used to isolate the phenoliccompounds from the aqueous methanolic extractof the S. nux-vomica leaves. Their identification was achievedthrough spectroscopic techniques. Cytotoxicity, analgesic, antipyreticand anti-inflammatoryactivitiesof S. nux-vomica leavesextractwere evaluated. Five phenoliccompounds were isolated and identified; Kaempferol-7 glucoside 1, 7-Hydroxy coumarin 2, Quercetin-3-rhamnoside 3, Kaempferol 3-rutinoside 4, and Rutin 5.

Furthermore, the cytotoxic activityof the extractwas evaluated againstdifferent cancer cell lines. The extractshowedpotentialcytotoxic activityagainsthuman epidermoid larynx carcinoma cells (Hep-2) and againstbreast carcinoma cell line (MCF-7). Colon carcinoma cells (HCT) were the least one affected by the extract. In addition, the extractexhibitedpromisinganalgesic, antipyreticas well as anti-inflammatoryactivities. It is concluded that, leavesextractof S. nux vomica possesspotentcytotoxic, analgesic, antipyreticand anti-inflammatoryactivities. These activitiescould be due to the presence of phenoliccompounds revealedby our phytochemicalinvestigations.

analgesicand anticonvulsant effectsof extractsfrom the leavesof Strychnos nux vomica linn

Strychnos nux vomica belongs to the family Loganiaceae is a fleshy herbaceous plantused in the Indian traditional medicineas nervine stomachic, tonic, aphrodiasic, spinal stimulant, also respiratory and cardiac stimulant. In excessive doses, it is a virulent poison producing titanic convulsions 1. In the present work, the analgesiceffectsof methylene chloride/methanol (I:I) (CH2Cl2/ CH3OH) extractand its hexane, methylene chloride (CH2Cl2), ethyl acetate, n-butanol fractionsand aqueous residue has been evaluated using acetic acid, formalin and pressure test. The anticonvulsant effectsof the CH 2Cl2/CH3OH extractwere also investigated on seizures inducedby pentylene tetrazole (PTZ 70 mg/kg), strychnine sulphate (STN 2.5 mg/kg) an thiosemicarbazide (TSC 50 mg/kg)CH2Cl 2/CH3OH extractand its fractions, administered orallyat the doses of 150 and 300mg/kg, exhibitedprotectiveeffectof at least 30% on the paininducedby acetic acid.

The CH2Cl2 fractionat 300 mg/kg showeda maximal effectof 78.49%. The CH2Cl 2/CH3OH extractand its CH2Cl2 fractionat the doses of 150 and 300 mg/kg significantlyreducedthe first phase of paininducedby formalin while the second phase was completely inhibited. The CH2Cl2 fractionproducedmore than 45% reductionin the sensitivity to paininducedby pressure. The CH2Cl 2/CH3OH extractof Strychnos nux vomica significantlyincreased the latency period in seizures inducedby PTZ and significantlyreducedthe duration of seizures inducedby the three convulsant agents. The extractprotected20% of animals againstdeath in seizures inducedby TSC and STN . These resultssuggest a peripheral and central analgesicactivitiesas well as an anticonvulsant effectof the leavesof Strychnos nux vomica.

Processing of Nux Vomica. VII. antinociceptiveeffectsof Crude alkaloidsfrom the Processed and Unprocessed seedsof Strychnos nux-vomica in Mice

We examined the antinociceptiveeffectsof the crude alkaloidfractions(CAF) of nux vomica (the dried seedsof Strychnos nux-vomica L.) and the influences of various processing methods upon their antinociceptionin three analgesictestsin mice. In the tail-pressure test, the CAF (0.01-1 μg/kg, i.p.) of nux vomica that was unprocessed or treatedwith sand-, licorice-, oil- or vinegar and sand-processing showedclear antinociception. The CAF (1 μg/kg, i.p.) of vinegar-processed nux vomica showedantinociception, withouteffectsat lower doses of 0.01 and 0.1 μg/kg and those treatedwith urine- or urine and sand-processing were withouteffectsat doses of 0.01-1 μg/kg. morphine(2 mg/kg, s.c.) showedshort-lasting antinociception, withouteffectsat a dose of 1 μg/kg. In the hot-plate test, the CAF (100 μg/kg, i.p.) of nux vomica having undergone sand-processing produceda significantantinociception, withouteffectsat lower doses of 0.01 and 1 μg/kg. The CAF (0.01-100 μg/kg, i.p.) of nux vomica that was unprocessed or treatedwith oil- or vinegar and sand-processing and morphine(1 and 100 μg/kg, s.c.) were withouteffects.

In the acetic acid-inducedwrithingtest, the CAF (1 μg/kg, i.p.) of nux vomica that was treatedwith sand-processing significantlyinhibitedthe writhingbehavior, while those of nux vomica that was unprocessed or treatedwith oil- or vinegar and sand-processing and morphinewere withouteffectsat a dose of 1 μg/kg. The present resultsdemonstratethe antinociceptiveeffectsof the CAF of nux vomica and suggest that sand-processing is good for the analgesicpotency of nux vomica. It is also suggested that the CAF of nux vomica has distinct antinociceptivepotency, even after treatmentwith licorice-, oil-, vinegar and sand-processing.

analgesicand anti-inflammatoryeffectsof the dry matter of culture broth of Termitomyces albuminosus and its extracts

Aim of the study : The objectives of this study were to investigate the analgesicand anti-inflammatoryeffectsof the dry matter of culture broth (DMCB) of Termitomyces albuminosus in submerged culture and its crude saponin extract(CSE) and crude polysaccharide extract(CPE).

Materials and methods : The analgesiceffectsof DMCB, CSE and CPE were evaluated with models of acetic acid-inducedwrithingresponse and formalin test in mouse. The anti-inflammatoryeffectsof DMCB, CSE and CPE were evaluated by using models of xylene-inducedmouse ear swellingand carrageen-inducedmouse paw edema.

Results :The DMCB, CSE and CPE significantlydecreasedthe acetic acid-inducedwrithingresponse and the licking time on the late phase in the formalin test. treatmentof DMCB (1000 mg/kg), CSE (200 mg/kg) or CPE (200 mg/kg) inhibitedthe mouse ear swellingby 61.8%, 79.0% and 81.6%, respectively. In the carrageen-inducedmouse paw edematest, the group treatedwith indomethacin showedthe strongestinhibitionof edemaformation by 77.8% in the third hour after carrageenan administration, while DMCB (1000 mg/kg), CSE (200 mg/kg) and CPE (200 mg/kg) showed48.4%, 55.6% and 40.5%, respectively.

Conclusion: The resultssuggested that DMCB of Termitomyces albuminosus possessed the analgesicand anti-inflammatoryactivities. Saponins and polysaccharides were proposed to be the majoractiveconstituents of Termitomyces albuminosus in submerged culture.

Tetrahydropalmatine

L-Tetrahydropalmatine alleviatesmechanical hyperalgesiain models of chronicinflammatoryand neuropathicpainin mice

Chronicpainis categorized as inflammatoryand neuropathic, and there are common mechanismsunderlying the generation of each painstate. Such painis difficult to treatand the treatmentat present is inadequate. Corydalis yanhusuo is a traditional Chinese medicinewith demonstratedanalgesicefficacyin humans. The potentialantihyperalgesic effectof its activecomponent is L-tetrahydropalmatine (L-THP). L-THP has been used for the treatmentof headache and other mild pain. However, little is known about its analgesiceffecton chronicpainand its mechanism. Here, we report that L-THP exertsremarkable antihyperalgesic effectson neuropathicand inflammatorypainin animal models. neuropathichypersensitivity was inducedby segmental spinal nerveligation and inflammatoryhypersensitivity was inducedby an intraplantar injection of complete Freund’s adjuvant.

To determine the receptormechanismunderlying the antihyperalgesic actionsof L-THP, we used SCH23390, an antagonistof a dopamineD1 receptor, in an attempt to block the antihyperalgesic effectsof L-THP. We foundthat L-THP (1-4 mg/kg, i.p.) produceda dose-dependent antihyperalgesic effectin spinal nerveligation and complete Freund’s adjuvant models. The antihyperalgesic effectsof L-THP were abolished by a dopamineD1 receptorantagonistSCH23390 (0.02 mg/kg).

Furthermore, L-THP (4 mg/kg, i.p.) did not influence motor function. These findingssuggest that L-THP may amelioratemechanical hyperalgesiaby enhancingdopamineD1 receptor-mediateddopaminergic transmission.

Thuja Orientalis (More Pankh)

EVALUATION OF anti-inflammatoryAND analgesicpotentialOF AQUEOUS METHANOLIC extractOF THUJA ORIENTALIS IN ALBINO RATS

This study was conducted for evaluating a naturalsource to treatinflammationand pain, to avoid the severeside effects of currently used agentsfor these ailments. Thuja Orientalis (More Pankh) is commonly used for the treatmentof pain and inflammatorydisordersin traditional medicine. Carrageenan inducedinflammatorymodel, acetic acid induced writhingtest and hot plate methods were used to evaluate anti-inflammatory, peripheral and central analgesicproperties of aqueous methanolic extractof Thuja Orientalis fruit(To-Cr) in albino rats. Completely randomized design (CRD) was constructed for the study and one way ANOVA was applied to compare means.

The resultsshowedthat TO-Cr has significantanti-inflammatoryand analgesicproperties

analgesicactivityof Thuja orientalis leaves

Present study reports analgesicactivityof petroleum ether, chloroform, methanolic and aqueous extractof leavesof Thuja orientalis. Hot plate and tail immersion methods were used for evaluation of central analgesicactivityand acetic acid inducedwrithingmodel was used for evaluation of peripheral analgesicactivity. Hot plate acetic acid inducedwrithingmodel was used for evaluation of central analgesicactivityas well as peripheral analgesicactivity.

Resultsindicate that petroleum ether extractof leavesat 50 mg/kg, i.p. dose produceda significantincreasein reactiontime (P<0.05) in tail immersion method and increased in response latency period (P<0.05) in hot plate method, againststandard drug pentazocin. Aqueous extractof leavesof Thuja orientalis significantly(P<0.05) attenuatedthe number of writhingwhen compared to standard drug paracetamol in acetic acid inducedwrithingmodel.

Edible medicinaland Non-medicinalplants

100 coloured illustrations in this volume. Referenced up-to-date-information on nutritiveand medicinalproperties, and other non-edible uses botanicaldescription and common and vernacular names to help in plantidentification medicaland scientific glossaries.

analgesicand anti-inflammatoryeffectof UP3005, a botanicalcomposition Containing two standardized extractsof Uncaria gambir and Morus alba

Background: Osteoarthritis(OA) is a chronicdebilitating degenerativejointdisease characterized by cartilage degradation and synovial inflammationexhibitedby clinical symptoms such as jointswelling, synovitis, and inflammatorypain. Present day painrelieftherapeuticsheavily relies on the use of prescription and over the counter nonsteroidalanti-inflammatorydrugs as the first line of defense where their long-term usage causesdetrimental gastrointestinal and cardiovascular-related side-effects. As a result, the need for evidencebased safer and efficaciousalternatives from naturalsources to overcome the mostprominent and disabling symptoms of arthritisis a necessity.

Materials and Methods: Describe the anti-inflammatoryand analgesiceffectof UP3005, a composition that contains a standardized blend of two extractsfrom the leafof Uncaria gambir and the root barkof Morus alba in carrageenan-inducedrat paw edema, abdominal constriction (writhing’s) and ear swellingassays in mouse with oraldose ranges of 100–400 mg/kg.

Results: In vivo, statistically significantimprovementin painresistance, and suppression of paw edemaand ear thickness in animals treatedwith UP3005 were observedcompared with vehicle-treateddiseased rats and mice. Ibuprofen was used a reference compound in all the studies. In vitro, enzymatic inhibitionactivitiesof UP3005 were determined with IC50 valuesof 12.4 μg/ml, 39.8 μg/ml and 13.6 μg/ml in cyclooxygenase-2 (COX-1), COX-2 and lipoxygenase (5-LOX) enzyme activityassay, respectively.

Conclusions: These data suggest that UP3005, analgesicand anti-inflammatoryagentof botanicalorigin with balanced dual COX-LOX inhibitionactivity, could potentially be used for symptom management of OA.

Uncaria gambir (W. Hunter) Roxb: From phytochemicalcomposition to pharmacological importance

Purpose:To present an overview of the ethnopharmacology, phytochemistry, and pharmacological effectsof the ‘wonder’ plant, Uncaria gambir (W. Hunter) Roxb.

Methods: The literature search for information on phytochemicalcomposition and pharmacological importance of U. gambir was undertaken using diverse electronic search engines, including Google, Scopus, Web of Science, scientific literature, and databases (Pubmed, Springer and Science Direct). Other relevant literature sources include books, book chapters, conference papers, theses, and other scientific publications.

Results: Uncaria gambir Roxb possessessignificantmedicinalpotentials as an antioxidant, anthelmintic, antibacterial, anti-diabetic, and for the management of osteoarthritis. Interest has increased among researchers for the utilization of this plantin complementary medicine, for example, to relievesore throat, spongy gum, and dysentery, to treatatherosclerosis and obesity, and to prolong sexual intercourse.

Conclusion: Uncaria gambir demonstrates significantpharmacological properties.  This review will be useful for prospective research and development of this ethnomedicinalplantinto potentially valuablehealthproducts.

Gambir extract(Uncaria Gambir) decreases inflammatoryResponse and increases Gastric Mucosal Integrity in Wistar Rats – Model Gastritis

Background:Uncaria gambir (local name: gambir) is a plantnative to Sumatera, Malaya and Borneo. This plantis potentialas local wisdom for therapeutics. In Sumatera, gambir was used as a traditional treatmentfor fever, diarrhoea, diabetics and wound healing.

Aim:To explore the efficacyof gambir extracton TNF alpha level, prostaglandin E2 level, lesson area, body weight, lipid profile and leptin level in Wistar rat-model gastritis.

Methods:This study was an experimental study, with a pre-post-test control group design. The subjects in this study were 30 male rats, 8 weeks old, weight 150-200 gram. Rats were administered with gambir extractat the dose of 20, 40 and 80 mg/kg BW/day for 3 days. Gambir was extracted by maceration methods. Statistical analysis was performed by SPSS 18.

Results:Gambir extractat the dose of 80 mg/kg BW exhibitedthe highest efficacyin reducingTNF alpha level, lesion area and increasingprostaglandin E2 level compared to gambir extractat doses of 20 mg/kg BW, 400 mg/kg BW, negative control, and positive control.

Conclusion:Gambir extractwas effectivein reducingTNF alpha level, lesson area, and increasingprostaglandin E2 level in Wistar rat-model gastritis.

naturalanti-inflammatoryagentsfor painrelief

The use of both over-the-counter and prescription nonsteroidalmedicationsis frequently recommended in a typical neurosurgical practice. But persistent long-term use safety concerns must be considered when prescribing these medicationsfor chronicand degenerativepainconditions.

This article is a literature review of the biochemical pathwaysof inflammatorypain, the potentially serious side effectsof nonsteroidaldrugs and commonly used and clinically studied naturalalternative anti-inflammatorysupplements. Although nonsteroidalmedicationscan be effective, herbs and dietary supplements may offer a safer, and often an effective, alternative treatmentfor painrelief, especially for long-term use.

antinociceptiveand anti-inflammatoryeffectsof Urtica dioica leafextractin animal models

Objective:This study was aimed to examine the antinociceptiveand anti-inflammatoryeffectsof Urtica dioica leafextractin animal models.

Materials and Methods:Hydroalcoholic extractof the plantleaveswas prepared by percolation method. Male Swiss mice (25-35 g) and male Wistar rats (180-200 g) were randomly distributed in control, standard drug, and three experimental groups (n=6 in each group). Acetic acid-inducedwrithing, formalin test, and carrageenan-inducedpaw edemawere used to assess the antinociceptiveand anti-inflammatoryeffects.

Results:The extractdose-dependently reducedacetic acid-inducedabdominal twitches. In formalin test, the extractat any of applied doses (100, 200, and 400 mg/kg) could not suppress the licking behavior of first phase while doses of 200 and 400 mg/kg significantlyinhibitedthe second phase of formalin test. In carrageenan test, the extractat a dose of 400 mg/kg significantlyinhibitedthe paw edemaby 26%.

Conclusion:The resultsconfirmthe folkloric use of the plantextractin painful and inflammatoryconditions. Further studiesare needed to characterize the activeconstituents and the mechanismof actionof the plantextract.

Evaluation of a root extractgel from Urtica dioica (Urticaceae) as analgesicand anti-inflammatorytherapyin rheumatoidarthritisin mice

Purpose:To develop and characterize an herbalgel prepared from methanol root extractof Urtica dioica (Urticaceae) (Stinging nettle) for the treatmentof arthritisin mice.

Methods:A methanol root extractfrom Urtica dioica was prepared, and a gel was then prepared using Carbopol 934. The prepared gel was subjected to various physicaltests(color, appearance, pH, texture, viscosity) and in vivo evaluation, including primary skinirritation, analgesic, and anti-inflammatorytests, in arthritic mice and compared with 2 % indomethacin gel, which was used as standard.

Results: The prepared herbalgel was of light gray color with a smooth texture. It showeda pH of 7.1 and a viscosity of 21.2 cps. The gel exhibitedpseudoplastic rheology, as evidenced by shear thinning with increased shear rate. It was non-irritating to the skinin primary skinirritation test in mice and showed55.05 % inhibitionof paw edemain a carrageenan-inducedhind rat paw edemamodel, comparable to that of the standard gel (53.93 %), after 24 h. The gel showed58.21 % analgesia, versus 61.19 % analgesiafor the indomethacin gel standard in writhingtest.

Conclusion: The topical gel from methanol root extractof U. dioica may be an efficaciousand safe alternative to non-steroidal anti-inflammatorydrugs in the treatmentof rheumatoidarthritisbut this requires further investigations to ascertain its safety and clinical efficacy.

antioxidant, antimicrobial, antiulcer and analgesicactivitiesof nettle (Urtica dioica L.)

In this study, water extractof nettle (Urtica dioica L.) (WEN) was studied for antioxidant, antimicrobial, antiulcer and analgesicproperties. The antioxidantpropertiesof WEN were evaluated using different antioxidanttests, including reducingpower, freeradicalscavenging, superoxide anion radicalscavenging, hydrogen peroxide scavenging, and metal chelating activities. WEN had powerful antioxidantactivity. The 50, 100 and 250 μg amounts of WEN showed39, 66 and 98% inhibitionon peroxidation of linoleic acid emulsion, respectively, while 60 μg/ml of α-tocopherol, exhibitedonly 30% inhibition. Moreover, WEN had effectivereducingpower, freeradicalscavenging, superoxide anion radicalscavenging, hydrogen peroxide scavenging, and metal chelating activitiesat the same concentrations.

Those various antioxidantactivitieswere compared to standard antioxidants such as butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), quercetin, and α-tocopherol. In addition, total phenoliccompounds in the WEN were determined as pyrocatechol equivalent. WEN also showedantimicrobial activityagainstnine microorganisms, antiulcer activityagainstethanol-inducedulcerogenesis and analgesiceffecton acetic acid-inducedstretching.

Stinging nettle (Urtica dioica L.): a reservoir of nutritionand bioactivecomponentswith great functional potential

In recent years a lot of the scientific interest has been concentrated on the identification of factors among low cost herbs that can be helpful in improvingthe healthof humans. A shocking feature of herbalanalysis has been that rarely any rare, exotic and exquisite planthas provedmore fascinating. Typically some common, less familiar, and disdained weed have been discovered to possessundreamt of virtues. Urtica dioica is a weed and its seeds, leavesand even rootsare used for medicinalpurpose.

It is a sensible reservoir of micronutrientsand nutritional elements which leads us to focus our study on this herb. Despite of being wholesome, leavesare easily digested and high in minerals (especially iron), vitamin C and pro-vitamin A. U.dioica is used as both medicineand food in many countries particularly in Mediterranean region because of being widespread and having conjointly exceptional biological activities. This comprehensive review is an effort to summarise the recent data on nutrition, pharmacological and clinical effectsof U. dioica keeping in view the increased demand by patients to use naturalproducts with antioxidantactivity, anti diabetic activityand having potentialfor treatmentof inflammatorydiseases.

The review of nutritional propertiesis also an importantaspect as every person needs general nutritional support in order to stay well or become optimally healthy. This review providesan overview of U. dioica in relation to antioxidantactivity, anti diabetic activity, antimutagenic activity, antimicrobial activity, analgesiceffectand treatmentof inflammatorydiseasesthat promotes its use.

analgesicand anti-inflammatoryeffectsof hydroalcoholic extractisolated from Semen vaccariae.

Semen vaccariae, the seedsof Vaccaria segetalis (Neck.) Garcke, is usually used as an importantmedicationfor female mammary gland diseases; it has also been used to promote lactation for centuries in China. The purpose of this work was to evaluate the analgesicand anti-inflammatoryeffectsof hydroalcoholic extractfrom semen vaccariae (HESV) with oraldoses of 50, 100 and 200mg/kg⋅bw in mice and rats. We observedthat the HESV could effectivelyinhibitacetic acid-inducedabdominal contractionand could elevate the latency time to thermal stimuli in the hot-plate test in mice. In the xylene-inducedear-swellingtest in mice, HESV could suppress the ear swelling. Additionally, HESV could significantlydecreasethe peritoneal capillary permeability and leukocyte infiltration in mice inducedby the intraperitoneal injection of acetic acid. HESV also significantlyreducedpaw thickness 2-4 hours after the injection of carrageenan in the carrageenan-inducedrat paw edematest.

This study was the first to demonstratethat the oraladministration of HESV might play an importantrole in the process of analgesiaand anti-inflammation, supporting its use for female mammary gland diseasesin traditional medicine.

Auricular Acupressure for analgesiain Perioperative Period of Total Knee Arthroplasty

Objective: We examined whether auricular acupressure (AA) can alleviatepostoperative painand decreasenarcotic consumption and its adverse effectsfor osteoarthritispatients after total knee arthroplasty (TKA).

Design: A prospective, randomized, sham control trial comparing AA and a sham control.

Setting: Department of Orthopedics, the first Hospital affiliated to Zhejiang University of Traditional Chinese medicine, Hangzhou, China.

Subjects:Ninety patients with degenerativeosteoarthritisundergoing TKA.

Interventions: The AA group received true AA by embedding vaccaria seedsat four specific AA points (knee joint, shenmen, subcortex, sympathesis) ipsilateral to the surgery site, while the control group received four nonacupuncture points on the auricular helix.

Outcome Measures: Visual analog scale (VAS), the consumption of analgesicvia patient-controlled analgesia, the incidence of analgesia-related adverse effects, Hospital for Special Surgery scores (HSS), and range of motion (ROM) were recorded.

Results:VAS scores were similar at 12, 24, 36, and 48 h postsurgery (P > 0.05), but AA group scores were lower than those of the control group at 3, 4, 5, and 7 days (P < 0.05). Patients in the AA group consumed lower doses of analgesicthan those in the control group after surgery (P < 0.05). The incidence of analgesia-related adverse effectsin the AA group was lower than that in the control group (P < 0.05). Although HSS scores were similar in the two groups preoperatively and at 3 months postoperatively (P > 0.05), HSS scores 2 weeks postoperatively were higher in the AA group than in the control group (P < 0.05), but there was no difference between groups in ROM (P > 0.05).

Conclusion: Applying auricular acupoint acupressure in the perioperative period of TKA is favorable for alleviatingpostoperative pain, decreasing opioidconsumption and its adverse effects, and promotingearly rehabilitation. Also, this intervention has the advantage of lower costs, fewer complications, simple application, and high safety.

A New Curcuminoid Compound Which Has potentanalgesicactivityagainstinflammatoryand neuropathicpain

The drug treatmentfor neuropathicpainremains a challenge due to poor efficacyand patient satisfaction. Curcumin has been reportedto alleviateneuropathicpain, but its clinical application is hindered by its low solubility and poor oralbioavailability. Curcumin diglutaric acid (CurDG) is a curcumin prodrug with improvedwater solubility and in vivo antinociceptiveeffects. In this study, we investigated the anti-inflammatorymechanismsunderlying the analgesiceffectof CurDG in the chronicconstriction injury(CCI)-inducedneuropathymouse model. Repeated oraladministration of CurDG at a low dose equivalent to 25 mg/kg/day produceda significantanalgesiceffectin this model, both anti-allodynic activityand anti-hyperalgesic activityappearing at day 3 and persisting until day 14 post-CCI surgery (p < 0.001) while having no significanteffecton the motor performance.

Moreover, the repeated administration of CurDG diminished the increased levels of the pro-inflammatorycytokines: TNF-α and IL-6 in the sciaticnerveand the spinal cord at the lowest tested dose (equimolar to 25 mg/kg curcumin). This study providedpre-clinical evidenceto substantiate the potentialof pursuing the development of CurDG as an analgesicagentfor the treatmentof neuropathicpain.

antiinflammatoryand analgesicactionsof 4′,5,6-trihydroxy-3’7- dimethoxy flavone-from Vicoa indica DC

Objective:To evaluate the antiinflammatory-analgesicproperty of the 4′,5,6-trihydroxy-3′,7-dimethoxy flavonefrom Vicoa indica DC using different agentsand models.

Methods:antiinflammatoryeffectswere producedby different inflammatoryagentsand after 4 hours the hind paw of the animals were sacrified and weighed in a torsion balance. analgesiceffectswere assessed by using different models and by acetic acid. In the former the analgesiceffectwas noted for a stipulated period of time and in the latter the writhings was counted for 15 minutes.

Results:The drug 4′,5,6- trihydroxy-3′,7-dimethoxy flavoneat 50 mg/kg body weight was very effectivein producing inhibitionin both antiinflammatory-analgesicmodels.

Conclusion:This drug recorded consistent inhibitoryand antiodema effectsin the different agentsused for the study.

anti-inflammatoryand analgesiceffectsof Cucurbitacins from Wilbrandia ebracteata

The anti-inflammatoryand antinociceptiveactionsof the CH₂Cl₂ extractand semipurified fraction(F-III) from rootsof Wilbrandia ebracteata Cogn. have been investigated in rats and mice. The CH₂Cl₂ extract(1-10 mg/kg, i.p.; ID₅₀ 5 mg/kg) and (3-30 mg/kg, p.o.; ID₅₀ 15 mg/kg) inhibited, in a dose-related manner, carrageenan-inducedpaw edemain rats. The subfraction(F-III) from CH₂Cl₂ extractand compounds isolated as cucurbitacin B and E also inhibitedcarrageenan-inducededema. The CH₂Cl₂ extractand F-III also exhibitedsignificantanalgesicactionin acetic acid-inducedpainin mice. In the formalin test, the CH₂Cl₂ extract(0.3-10 mg/kg, i.p.) and (3-30 mg/kg, p.o.) causedinhibitionof the neurogenic(first phase) and inflammatoryphase (second phase) of formalin-inducedpain. However, the CH₂Cl₂ extractwas more effectivein relation to the second phase than in inhibitionof the formalin-inducededema.

These findingssuggest that CH₂Cl₂ extracthas potentanti-inflammatoryand analgesicactionand that F-III and cucurbitacin B and E may account for these actions.

treatmentof low back painexacerbations with willow barkextract: a randomized double-blind study

Purpose: herbalmedicinesare widely used for the treatmentof pain, although there is not much information on their effectiveness. This study was designed to evaluate the effectiveness of willow (Salix) barkextract, which is widely used in Europe, for the treatmentof low back pain.

Subjects and Methods :We enrolled 210 patients with an exacerbation of chroniclow back painwho reportedcurrent painof 5 or more (out of 10) on a visual analog scale. They were randomly assigned to receive an oralwillow barkextractwith either 120 mg (low dose) or 240 mg (high dose) of salicin, or placebo, with tramadol as the sole rescue medication, in a 4-week blinded trial. The principal outcome measure was the proportion of patients who were pain-freewithouttramadol for at least 5 days during the final week of the study.

Results: The treatmentand placebo groups were similar at baseline in 114 of 120 clinical features. A total of 191 patients completed the study. The numbers of pain-freepatients in the last week of treatmentwere 27 (39%) of 65 in the group receiving high-dose extract, 15 (21%) of 67 in the group receiving low-dose extract, and 4 (6%) of 59 in the placebo group (P <0.001). The response in the high-dose group was evident after only 1 week of treatment. significantlymore patients in the placebo group required tramadol (P <0.001) during each week of the study. One patient suffered a severeallergic reaction, perhaps to the extract.

Conclusion:Willow barkextractmay be a useful and safe treatmentfor low back pain.

Methanol extractsof Xanthium Sibiricum rootsinhibitthe inflammatoryresponses via the inhibitionof NF-κB and STAT3 activation in murine macrophages

Ethnopharmacological relevance:Xanthium sibiricum has been used as a traditional Chinese medicinefor the treatmentof appendicitis, bronchitis, arthritis, and other inflammatoryailments. However, its pharmacological activityrelated to an anti-inflammatoryeffectremain unknown. This present study aims to investigate the anti-inflammatoryeffectof methanol extractsof X. sibiricum roots(MXS), and to further determine its underlying mechanismof actionin order to assess the medicinalvalueof X. sibiricum roots.

Materials and methods:To assess the anti-inflammatoryactivityof MXS in lipopolysaccharides (LPS)-stimulated RAW 264.7 macrophages, the production of nitric oxide (NO) was measured using the Griess reagentsystem. The levels of pro-inflammatorycytokinesand mediators were quantified using an Enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction(RT-PCR). Subsequently, immunoblotting analyses were employed to detect inflammatorymediators as well as to elucidate the underlying regulatory mechanismssuppressedby MXS.

Results: MXS inhibitedLPS-stimulated NO production and inducible nitric oxide synthase (iNOS) expressionin RAW 264.7 macrophages within the non-cytotoxic concentration range (50-400 μg/ml). In addition, mRNA and protein levels of pro-inflammatorycytokinessuch as interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α were significantlysuppressedby MXS at the concentration of 400 μg/ml. Furthermore, MXS (200 μg/ml) clearly reducedthe phosphorylation levels of the inhibitorof kappa Bα (IκBα) and signal transducer and activator of transcription 3 (STAT3), withoutaffecting changes in the phosphorylation levels of mitogen-activated protein kinases (MAPKs). When five majorcomponents(betulin, betulinic acid, β-sitosterol, stigmasterol, and scopoletin) of MXS were separately investigated, stigmasterol and β-sitosterol seemed to play majorinhibitoryroles in the LPS-inducedproduction of inflammatorymediators such as NO, IL-6, and TNF-α.

Conclusion:Our resultsdemonstratethat MXS has an anti-inflammatoryproperty in LPS-stimulated RAW 264.7 macrophages, and its anti-inflammatoryactivityis exertedby the regulation of nuclear factor-κB (NF-κB) and STAT3 signaling pathways.

Determination of TPA Content in Xanthium sibiricum Patrin ex Widder and Its anti-inflammatoryeffect

Objective:To establish a method of determining the content of total phenolicacid in Xanthium sibiricum Patrin ex Widder and investigate its anti-inflammatoryaction.

Methods:Chlorogenic acid was used as reference substance and diluted with 50% methanol solution to constant volume. The absorbancy was determined at wavelength of 426 nm by ultraviolet spectroscopy. With aspirin as positive control, the anti-inflammatoryactionof Xanthium sibiricum Patrin ex Widder was studied by ear swellingcausedby xylene in mice.

Results: The average content of total phenolicacid in Xanthium sibiricum Patrin ex Widder was 5.22% and the RSD reached 0.17%. It could significantlyrelieveear swellingcausedby xylene in mice. Compared with normal saline, the resultwas of significantdifference (P < 0.01).

Conclusion: The method was convenient and accurate, so it could be used to measure the content of total phenolicacid in Xanthium sibiricum Patrin ex Widder and explore its anti-inflammatoryaction.

Bioactivity-guided fractionation for anti-inflammatoryand analgesicpropertiesand constituents of Xanthium strumarium L.

The aim of this study was to fractionate an extractof Xanthium strumarium L. (EXS) and to investigate the anti-inflammatoryand analgesicpropertiesof the extractand its fractions. The ethanol extractof X. strumarium (EXS) was fractionatedon the basis of polarity. Among the different fractions, the n-butanol fractionshowedthe highest anti-inflammatoryactivityin the croton-oil-inducedear edematest and furthermore reducedthe number of writhings inducedby acetic acid in mice in a dose-dependent manner. This indicates that the n-butanol fractionof X. strumarium possessespotentanalgesiceffectswhich are likely to be mediatedby its anti-inflammatoryactivity.

Bioassay-guided fractionation of EXS led to the isolation and identification of ten caffeoylquinic acids and three heterocyclics by HPLC–DAD–MSn from the activen-butanol fraction, implying that the activecompounds are polar in nature. The isolated caffeoylquinic acids could partially explain the antinociceptiveeffectof X. strumarium polar extract.

analgesiceffectof Zanthoxylum nitidum extractin inflammatorypainModels Through Targeting of ERK and NF-κB Signaling

Background: Zanthoxylum nitidum (Roxb.) DC., also named Liang Mianzhen (LMZ), one kind of Chinese herbcharacterized with anti-inflammatoryand relievingpainpotency, which is widely used to treatinjuries, rheumatism, arthralgia, stomach painand so on in China. But its mechanismrelated to the anti-hyperalgesic has not been reported. The aim of this study was to investigate the analgesicactivityof Liang Mianzhen on mice with Complete Freund adjuvant (CFA)-inducedchronicinflammatorypain. Meanwhile, the peripheral and central mechanismsof analgesiceffectof Liang Mianzhen were further examined via observing the effectsof Liang Mianzhen on the signal pathway associated with inflammatoryinducedhyperalgesia.
Methods: The inflammatorypainmodel was established by intraplantar injection of CFA in C57BL/6J mice. After 1 day of CFA injection, the mice were treatedwith LMZ (100 mg/kg) for seven consecutive days, and the behavioraltestswere measured after the daily intragastric administration of LMZ. The morphological changes on inflamed paw sections were determined by hematoxylin eosin (HE) staining. Changes in the mRNA expressionlevels of tumor necrosis factor (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and nuclear factor κB p65 (NF-κBp65) were measured on day seven after CFA injection by using real-time quantitative PCR analysis and enzyme linked immunosorbent assay (ELISA) method, respectively. Moreover, immunohistochemistry and western blotting were used to detect extracellular regulated protein kinases 1/2 (ERK1/2) and NF-κB signal pathway activation.
Results: The extractof LMZ (100 mg/kg) showeda significantanti-inflammatoryand analgesiceffectin the mice model. The paw edemavolume was significantlyreducedafter the administration of LMZ compared to CFA group, as well as the paw tissues inflammatorydamage was relived and the numbers of neutrophils in mice was reducedsignificantly. The CFA-inducedmechanical threshold and thermal hyperalgesiavaluewere significantimprovedwith LMZ treatmentat day three to day seven. We also foundthe mRNA levels of TNF-α, IL-1β, IL-6 and NF-κBp65 were down-regulate after 7 days from the LMZ treatmentcompared to CFA group. Meanwhile, LMZ significantlysuppressedover-expressionof the phosphorylation of ERK1/2 and NF-κBp65 in peripheral and central.
Conclusion: The present study suggests that the extractof LMZ attenuates CFA-inducedinflammatorypainby suppressing the ERK1/2 and NF-κB signaling pathway at both peripheral and central level.

[Comparative Study on effectsof Anti-contusion injury, analgesiaand anti-inflammationof Root and stemof Zanthoxylum nitidum].

Objective: To providethe scientific evidencefor expansion of medicinalpartsof Zanthoxylum nitidum by comparing the effectsof anti-contusion injury, analgesiaand anti-inflammationof its root and stem.

Methods: The pharmacological effectsbetween root and stemof Zanthoxylum nitidum were compared by observing the anti-injuryeffectin rats with injurystruck by hammer. The analgesiceffectin mice was evaluated by writhingtest and hot plate test, and the anti-inflammatoryeffecton paw edemainducedby carrageenan and granuloma inducedby cotton pellet were investigated in rats.

Results: Both root and stemof Zanthoxylum nitidum relievedthe exterior and histological symptoms of rats’ injurylegs struck by hammer, decreasedthe numbers of mice’s writhing, enhancedpainthreshold of mice on heat plate, inhibitedthe edemaof rats inducedby carrageenan, and suppressedthe granuloma of rats inducedby cotton pellet.

Conclusion: Stemof Zanthoxylum nitidum has similar effectsof anti-contusion injury, analgesiaand anti-inflammationwith root of Zanthoxylum nitidum.

antinociceptiveactivityof Rhoifoline A from the ethanol extractof Zanthoxylum nitidum in mice

Aim of the study: Antinociceptiveactivityof Rhoifoline A (RA), a benzophenanthridine alkaloidobtained from the ethanol extractof Zanthoxylum nitidum, was evaluated in mice using chemical and thermal models of nociception.

Materials and methods: RA was evaluated on anti-nociceptiveactivityin mice using chemical and thermal models of nociception.

Results: RA administered intraperitoneally at doses of 10, 20, 40 and 80 mg/kg exhibitedsignificantinhibitions on chemical nociceptioninducedby intraperitoneal acetic acid and subplantar formalin, and on thermal nociceptionin the tail-flick test and the hot plate test. RA neither significantlyimpaired motor coordination in the rotarod test nor did spontaneous locomotion in the open-field test. RA did not enhancethe pentobarbital sodium inducedsleep time. These resultsindicated that the observedantinociceptiveactivityof RA was unrelated to sedation or motor abnormality. Core body temperature measurement showedthat RA did not affect temperature during a 2-hour period. Furthermore, RA-inducedantinociceptionin the hot plate test was insensitive to naloxone or glibenclamide but significantlyantagonized by L-NAME, methylene blue and nimodipine.

Conclusion: Therefore, it is reasonable that the analgesicmechanismof RA possibly involved the NO-cGMP signaling pathway and L-type Ca2+ channels.

analgesiceffectof the Lignans Compound Crystal-8 from Zanthoxylum Nitidum ( Roxb. ) DC. and the Relationship between Crystal-8 and receptors

Objective:To study whether crystal-8 exertsanalgesiceffecton the central nervous system,and to observe the relationship between crystal-8 and receptors.

Methods:A total of 32 SD rats were randomly divided into the 0.9% sodium chloride solution group, positive control group ( rotundine 2 mg·kg-1 ) , high dose of crystal-8 group ( 2 mg·kg-1 ) and low dose of crystal-8 group ( 1 mg · kg-1 ) . The changes of painthreshold were measured by the thermal stimulation test following intracerebroventricular (ICV) injection.The SD rats or mice were randomly divided into the 0.9% sodium chloride solution group, receptortool medicinegroup ( including naloxone, reserpine, haloperidol, scopolamine) , crystal-8 group, receptortool medicineplus crystal-8 group. The painthreshold was detected by the thermal stimulation test at 15, 30, 45, 60, 90, 120 min after dosing, then the influence of analgesiceffectof crystal-8 on the neurotransmitter was observed.

Results:Compared with the 0.9% sodium chloride solution group, the painthreshold of rats was improvedafter taking the crystal-8 by intracerebroventricular (ICV) injection(P<0.01).Compared with the crystal-8 group, the naloxone plus crystal-8 group, the haloperidol plus crystal-8 group, the scopolamine plus crystal-8 group couldn’t increasethe painthreshold, there was no significantdifference among these groups(P>0.05).However, Reserpine plus crystal-8 group could significantlydecreasethe painthreshold in rats compared with the crystal-8 group(P<0.01).The analgesiceffectof crystal-8 was interfered by reserpine.

Conclusion:The analgesiceffectof crystal-8 may be involved in the central mechanism,which relates to monoamine neurotransmitters, but has nothing to do with the opioidreceptor, M receptor, and the inhibitionof central DA receptor.

[studieson the antispasmodic and analgesicactionsof crystal-8 isolated from Zanthoxylum nitidum (ROXB.) DC].

effectsof a ginger extracton knee painin patients with osteoarthritis