Number Of Acetic Acid-induced Writhes Research Articles

Schinus terebinthifolia leaf lectin has central and peripheral antinociceptive action mediated by its carbohydrate-recognition domain and delta-opioid receptors

Ethnopharmacological relevancePreparations from the bark and leaves of Schinus terebinthifolia Raddi are commonly used to treat toothaches and sore throats. The use of medications based on leaves of this plant has also been reported for pain of arthritis, toothache, and sore throat. Some evidence indicated that the lectin SteLL is an antinociceptive agent from leaves. Aim of the studyThis study evaluated the antinociceptive activity of S. terebinthifolia leaf lectin (SteLL) using mouse models of peripheral and central nociception. Materials and methodsAnimals were treated intraperitoneally with SteLL at 1, 5, and 10 mg/kg. An acetic acid-induced abdominal writhing test was performed to screen for the antinociceptive effect of the lectin. Next, the formalin test was used to assess the effects of SteLL on neurogenic (first phase) and inflammatory (second phase) pain, as well as to investigate the involvement of the carbohydrate-recognition domain (CRD) of SteLL and opioid receptors in the antinociceptive effect. The tail immersion test was performed to assess the central antinociception. Additionally, a rotarod test was performed to evaluate the effects of lectin on motor coordination in mice. ResultsSteLL reduced the number of acetic acid-induced writhes by 83.5–100.0%. In the first phase of the formalin test, SteLL reduced paw licking time by 49.4–50.5%, while in the second phase, SteLL reduced paw licking time by 80.5–82.6%. This antinociceptive effect was reversed by the previous incubation of the lectin with ovalbumin (indicating the possible involvement of the CRD) and by the administration of naloxone, a nonselective opioid receptor antagonist. When testing selective antagonists of opioid receptors (μ, δ, and κ), only naltrindole, a selective δ receptor antagonist, blocked the antinociceptive action of SteLL during the second phase of the formalin test. In the tail immersion test, SteLL (1, 5, and 10 mg/kg) administration reduced sensitivity to thermal stimulus, which was observed even after 2 h. SteLL (10 mg/kg) did not affect animal motor coordination in rotarod test when compared to the control group. ConclusionSteLL has peripheral and central analgesic action involving opioid receptor modulation without affecting the motor coordination of animals. These results provide new perspectives for developing analgesic agents using lectins.

Analgesic, anti-inflammatory and antipyretic studies on the residual aqueous fraction of Uapaca togoensis (Pax) stem bark in rodents

Uapaca togoensis Pax. (Euphorbiaceae) is used in traditional medicine to treat several diseases including pain, inflammation and fever. This study investigated analgesic, anti-inflammatory and anti-pyretic effects of the residual aqueous fraction of the plant. Preliminary phytochemical screening and acute toxicity studies were conducted. Analgesic activity was evaluated using acetic acid-induced writhing, hot plate and formalin-induced pain tests at doses of 250, 500 and 1000 mg/kg, p.o. Anti-inflammatory and antipyretic activities were investigated using carrageenaninduced paw edema and Brewer’s yeast-induced pyrexia model respectively in rats. Oral median lethal dose of the fraction was found to be greater than 5000 mg/kg. The fraction significantly (p<0.05) reduced the number of acetic acid-induced writhes and increased the reaction time of mice to thermal stimuli. In the formalin test, a significant (p<0.05) reduction in mean pain score was observed at the second phase. A significant (p<0.05) decrease in paw edema at the 4th and 5th hours and a reduction in temperature was also observed at the 22nd hour. Phytochemical screening revealed the presence of saponins, tannins, steroids, cardiac glycosides, flavonoids, alkaloids and triterpenes. The result of the study revealed that the fraction possesses analgesic, anti-inflammatory and antipyretic activities, validating the folkloric use of the plant.
 Keywords: Analgesic, Anti-inflammatory, Anti-pyretic, Uapaca togoensis, Residual Aqueous Fraction

Phytochemical composition of essential oils from Cinnamomum camphora leaves of different areas and their analgesic properties

This article was aimed to analyze the essential oils from Cinnamomum camphora leaves of four areas by GC-MS and to study their analgesic properties. Analgesia test was performed employing mouse acetic acid writhing method, hot plate method and reserpine induced migraine model, and plasma and brain tissue NO and prostaglandin E2 (PGE2) contents were determined. The major compounds from essential oils of Suzhou C. camphora leaves (SZ), Nanjing C. camphora leaves (NJ), Nantong C. camphora leaves (NT) and Lianyungang C. camphora leaves (LY) are different, but they all consist of nerolidol and (E)--atlantone. (E)--atlantone exists as the main constituent and it is first reported in this plant. In the hot plate test, NJ or LY (1 ml×kg-1 each) significantly prolonged the reaction time after 30 min treatment and plasma and brain tissue NO and PGE2 in the mice with NJ or LY (1 ml•kg-1) administration were significantly decreased. In the acetic acid-induced writhing test, NJ (1 ml×kg-1 each) significantly decreased the number of acetic acid-induced writhes in mice compared to the animals that received vehicle only. In the migraine test, Plasma NO in the mice with NJ or NT (1 ml×kg-1) and NJ (0.25 ml×kg-1) administration were significantly decreased. NJ and LY have obvious analgesic effect and the mechanism is related to the reduction of central and peripheral NO and PGE2 levels. NJ was effective on migraine mice induced by reserpine and the mechanism may be related to the inductionof NO release. NJ and LY have significantly analgesic effects in three experimental models of pain.

Analgesic and antiinflammatory activities of the essential oil from Artemisia sieberi Besser

The analgesic activity of Artemisia sieberi oil was assessed by acetic acid-induced writhing test and Eddy’s hot plate method; while the acute anti-inflammatory effect was investigated by inflammatory paw edema test in rats. The administration rout of the essential oil, standard drugs and the vehicle used in all assays was intraperitoneal injection. The 1 and 2.5 mg/kg doses of the studied oil significantly decreased the number of acetic acid-induced writhes in mice. The dose of 1 mg/kg of the oil also exhibited a central analgesic effect as evidenced by a significant increase in reaction time at several time points after 15 min treatment in the hot plate method. In addition, the 1 mg/kg dose of the oil significantly reduced carrageenan induced paw edema in rats at the first hour of the test by 72.7% inhibition and lasted to the third hour of the test by 74.3% inhibition found to be very close to that of the standard drug, diclofenac sodium (50 mg/kg). The major components of the oil were characterized as camphor (31.2%) and 1,8-cineole (20.0%). The results suggest that A. sieberi essential oil has a significant effect against acute inflammation and has central and peripheral anti-nociceptive effects.

Antinociceptive and anti-inflammatory properties of Tetracera alnifolia Willd. (Dilleniaceae) hydroethanolic leaf extract.

Background Tetracera alnifolia Willd. (Dilleniaceae) is used in traditional African Medicine for the treatment of headache, abdominal pain, and rheumatism. Hence, this study sought to investigate the antinociceptive and anti-inflammatory effects of the hydroethanolic leaf extract of T. alnifolia (HeTA) in rodents. Methods Antinociceptive activity was evaluated using the acetic acid-induced writhing, formalin-/capsaicin-induced paw licking and hot plate tests in mice. The contribution of opioidergic, l-arginine-nitric oxide, and ATP-sensitive potassium channel pathways in HeTA-induced antinociception was also evaluated. The anti-inflammatory effect was assessed using the carrageenan-induced paw edema, xylene ear edema, cotton pellet granuloma, and complete Freund's adjuvant (CFA)-induced arthritis in rats. Results HeTA (100, 200, and 400 mg/kg, p.o.) produced significant (p<0.05) decrease in mean number of acetic acid-induced writhing, time spent licking paw in formalin, and capsaicin tests as well as time course increase in nociceptive reaction latency in hot plate test. HeTA-induced antinociception was prevented by pretreatment of mice with naloxone (non-selective opioid receptor antagonist), l-arginine (nitric oxide precursor), or glibenclamide (ATP-sensitive potassium channel blocker). HeTA (100 mg/kg, p.o.) produced a significant anti-inflammatory effect against carrageenan-induced rat paw edema (1-5 h), xylene-induced ear edema, cotton pellet-induced granuloma formation, and CFA-induced arthritis in rats. The effects of HeTA in various models were similar to the effect of the standard reference drugs. Conclusions Findings from this study showed that HeTA possesses antinociceptive effect possibly mediated through peripheral opioid receptors with activation of l-arginine-nitric oxide and ATP-sensitive potassium channel pathway as well as anti-inflammatory activity.

Calycophyllum spruceanum BENTH ameliorates acute inflammation in mice

Ethnopharmacological relevanceCalycophyllum spruceanum (Benth.) Hook. F. ex K. Schum. is widely distributed in the Amazonian region of Brazil, where it is popularly known as “mulateiro”, “pau-mulato”, “pau-mulato-de-várzea”, “escorrega-macaco” or “pau-marfim”. Preparations of C. spruceanum barks are used in the form of tea, poultice or skin patches to treat stomach diseases, skin inflammation and uterus tumors. Purpose of the studyTo investigate in vivo the antinociceptive and anti-inflammatory activities of the hydroalcoholic extract of Calycophyllum spruceanum barks (HECSb) in order to validate its popular usage in inflammatory conditions. Materials and methodsChemical analysis of HECSb was performed using the UHPLC-MS system. Mice were treated per oral with HECSb (5–5000 mg/kg) and evaluated for acute toxicity (during 15 days); motor activity (Rota rod test); body weight (up to 72 h); antinociceptive activity: writhes induced by 0.8% acetic acid; paw licking induced by 2.5% formalin; paw withdrawal (von Frey test) induced by carrageenan (300 μg) or PGE2 (100 ng); anti-inflammatory (paw edema model). For histopathological analysis subplantar tissue fragments were collected 1 h after paw edema induction. ResultsHECSb chemical analysis revealed the presence of caffeoylquinic derivatives, small organic acids, and phenolic compounds. HECSb showed antinociceptive effect, reducing the number of acetic acid-induced writhes by 72% at 120 mg/kg, paw licking (phase 2- Formalin test) by 33% at 60 mg/kg and 49% at 120 mg/kg; and paw withdrawal elicited by carrageenan (53% at 120 mg/kg) and PGE2 (120 mg/kg) at 0.5 h (48%) and 1 h (45%). HECSb (120 mg/kg) also inhibited the paw edema elicited both by carrageenan (48%) and PGE2 (92%). Histopathological analysis (leukocyte infiltration, edema, focal areas of hemorrhage, vascular congestion) of HECSb treatment at 120 mg/kg demonstrated normal morphology [median 0 (0,1)] compared to PGE2, showing severe alterations [median 3 (2,3); p = 0,0035]. HECSb did not induce acute toxicity nor altered body mass or motor coordination. ConclusionsHECSb shows antinociceptive and anti-inflammatory effect in mice without inducing apparent acute toxicity.

Analgesic and Anti-inflammatory Activities of the Essential Oil from Artemisia aucheri Boiss

Artemisia aucheri is a native plant to the south of Iran and used as a pain killer and for the treatment of some inflammatory based disorders. Regarding the presence of high content of volatile terpenoids in the plant we were prompted to investigate the analgesic and antiinflammatory activities of the essential oil from A. aucheri aerial parts in the animal models. The oil was also analyzed by GC and GC-MS in order to identify the potentially responsible compounds for observed properties. The analgesic activity of the oil was assessed by acetic acid-induced writhing and Eddy's hot plate methods while the acute anti-inflammatory effect was investigated by inflammatory paw edema in rat. The studied oil significantly decreased the number of acetic acid-induced writhes in mice compared with animals that received vehicle only. It also exhibited a central analgesic effect as evidenced by a significant increase in reaction time in the hot plate method. The oil also significantly reduced carrageenan induced paw edema in rats. The major components of the oil were characterized as camphor (51.0%) and 1,8-cineol (25.0%), which might be responsible for these observed activities. The results suggest that A. aucheri essential oil possesses biologically active constituent(s) that have significant activity against acute inflammation and have central and peripheral antinociceptive effects which support the ethnomedicinal claims of the plant application in the management of pain and inflammation.

Evaluation of the analgesic effects of ammoxetine, a novel potent serotonin and norepinephrine reuptake inhibitor.

The selective serotonin (5-HT) and norepinephrine (NE) reuptake inhibitors (SNRIs) are commonly used for the treatment of neuropathic pain and fibromyalgia. Ammoxetine ((±)-3-(benzo[d] [1,3]dioxol-4-yloxy)-N-methyl-3-(thiophen-2-yl)propan-1-amine) has been identified as a novel potent SNRI. In this study, we evaluated the acute analgesic properties of ammoxetine in different animal models of pain, and examined the involvement of monoamines in its analgesic actions. The analgesic effects of ammoxetine were assayed using models of acetic acid- and formalin-induced pain in mice, neuropathic pain induced by sciatic nerve injury (SNI), chronic constriction injury (CCI) and reserpine-induced fibromyalgia pain in rats. The contents of 5-HT and NE in brain regions of fibromyalgia rats were measured using HPLC-ECD. In all the experiments, duloxetine was used as a positive control drug. Oral administration of ammoxetine (0.625-10 mg/kg) or duloxetine (2.5-40 mg/kg) dose-dependently decreased the number of acetic acid-induced writhing and formalin-induced first phase and second phase paw licking time in mice. Oral administration of ammoxetine (2.5-10 mg/kg) or duloxetine (10 mg/kg) alleviated mechanical allodynia in SNI and CCI rats and thermal hyperalgesia in CCI rats. The antiallodynic effect of ammoxetine in CCI rats was abolished by pretreatment with para-chlorophenylalanine methyl ester hydrochloride (PCPA, a 5-HT synthesis inhibitor) or α-methyl-para-tyrosine methylester (AMPT, a catecholamine synthesis inhibitor). Oral administration of ammoxetine (30 mg/kg) or duloxetine (50 mg/kg) significantly attenuated tactile allodynia in rats with reserpine-induced fibromyalgia. In the fibromyalgia rats, administration of ammoxetine (10, 30 mg/kg) or duloxetine (30, 50 mg/kg) dose-dependently increased the levels of 5-HT and NE, and decreased the metabolite ratio of 5-HT (5-HIAA/5-HT) in the spinal cord, hypothalamus, thalamus and prefrontal cortex. Ammoxetine effectively alleviates inflammatory, continuous, neuropathic and fibromyalgia-related pain in animal models, which can be attributed to enhanced neurotransmission of 5-HT and NE in the descending inhibitory systems.

Anti-inflammatory and analgesic activity of aqueous extracts of dried leaves of Murraya koenigii Linn.

Background: Murraya koenigii, commonly known as karipatta or curry leaf, is analgesic and can be used effectively against inflammation and itching. The various pharmacological activities such as vasodilation, antimicrobial, antidiabetic, antiulcer, analgesic, phagocytic, and antioxidant activities of this plant have also been reported. Aims and Objectives: To evaluate the anti-inflammatory and analgesic activity of aqueous extract of dried leaves of M. koenigii Linn. in male Wistar rats. Materials and Methods: Adult male Wistar rats (100–150 g body weight) were used in this study. Aqueous extract of M. koenigii Linn. was used to evaluate acute anti-inflammatory and analgesic activity by plethysmometer and hot plate method by oral administration at doses of 100, 300, and 500 mg/kg body weight in healthy albino rats. Result: In acute studies, the aqueous extract showed anti-inflammatory activity by significant reduction in the paw edema volume, in a dose-dependent manner when compared with the control and standard drug. Aqueous extract of M. koenigii Linn. significantly and dose-dependently reduced the number of acetic acid-induced writhing and significantly increased the latency of paw licking in hot plate method. Statistical analysis was carried out by one-way ANOVA, followed by Turkey's test. Conclusion: Aqueous extract of M. koenigii Linn. possesses both anti-inflammatory and analgesic activity in a dose-dependent manner.

Pharmacological evaluation of Mallotus philippinensis (Lam.) Muell.-Arg. fruit hair extract for anti-inflammatory, analgesic and hypnotic activity.

Objective:Recently, we observed wound healing activity of 50% ethanol extract of Mallotus philippinensis Muell. Arg (MP) fruit hairs extract (MPE). In several intestinal infections, localized inflammation is of common occurrence and hence we evaluated the anti-inflammatory, analgesic and hypnotic activity of MPE in different rat experimental models.Materials and Methods:Anti-inflammatory activity was evaluated by carrageenan (acute) and turpentine oil induced formalin (subacute) induced paw edema and while granuloma pouch (subacute) in rats. Analgesic and hypnotic activity of MPE was undertaken by tail-flick, hot-plate, and acetic acid-induced writhing tests while pentobarbitone-induced hypnotic potentiation in rats.Results:MPE at a dose of 200 mg/kg at 3 h after their administration showed inhibition of formalin-induced paw edema by 41.60% (P < 0.001) and carrageenan-induced paw edema by 55.30% (P < 0.001). After 7 days of treatments, MPE showed 38.0% (P < 0.001) inhibition against formalin-induced paw edema and reduced weight of turpentine-induced granuloma pouch by 29.6% (P < 0.01) and volume of exudates by 26.1% (P < 0.01), respectively. MPE (200 mg/kg) showed dose-dependent elevation in pain threshold and peak analgesic effect at 120 min as evidenced by increased latency period in tail flick method and increased reaction time in the hot-plate test while the reduction in the number of acetic acid-induced writhes by 45.7% (P < 0.001). The pentobarbitone-induced hypnosis model showed potentiation, as defined by increased duration of sleep in treated group rats as compared to control.Conclusion:Thus, the study revealed MPE is effective in reducing acute and subacute inflammation and showed effective and similar analgesic activity. This seemed to be safe in the treatment of pain and inflammation.

Analgesic, anti-inflammatory and anti-pyretic activities of D-3-O-methylchiroinositol isolated from stem bark of Piliostigma thonningii

D-3-O-methylchiroinositol isolated from the stem bark of Piliostigma thonningii was evaluated for analgesic, anti-inflammatory and anti-pyretic activities. The compound was screened for analgesic activity by the acetic acid-induced writhing and tail immersion tests. The anti-inflammatory activities were evaluated by the carrageenan-induced paw edema and Freund adjuvant-induced arthritis tests, while its anti-pyretic activity was determined using the yeast-induced pyrexia test. D-3-O-methylchiroinositol (10, 30 and 60 mg/kg) significantly (P < 0.01) reduced the number of acetic acid-induced writhing. In the tail immersion test, by 15, 45, 30 and 60 min post-treatment, tail withdrawal times in D-3-O-methylchiroinositol (30 and 60 mg/kg) were significantly (P < 0.01) longer compared to reaction times recorded in control group. The paw volumes obtained in the 60 mg/kg D-3-O-methylchiroinositol group by 1 h post-carrageenan injection were significantly (P < 0.05) lower than the paw volume of control rats. At 2 and 3 h, the paw volumes in the D-3-O-methylchiroinositol (10, 30 and 60 mg/kg) were significantly (P < 0.05) lower than paw volume of the control group. In the subacute phase of arthritis (18 h), paw volumes in D-3-O-methylchiroinositol (30 and 60 mg/kg) were significantly (P < 0.05 and P < 0.01, respectively) lower compared to paw volume in the control group. In the chronic phase (30 days) of arthritis, paw volumes in the D-3-O-methylchiroinositol (10, 30 and 60 mg/kg) were significantly (P < 0.01) lower than paw volume of the control group. The rectal temperatures of the 60 mg/kg D-3-O-methylchiroinositol were significantly lower at 1, 2, 3, 4 and 5 h post-yeast injection compared to those of the control. The findings of this study establish that D-3-O-methylchiroinositol has analgesic, anti-inflammatory and anti-pyretic activities.

Antinociceptive activity of Sargassum polyceratium and the isolation of its chemical components

Marine algae have been the focus of important studies over the past fifty years, with a considerable number of components important to chemists and taxonomists having been isolated and characterized. The scientific data available on Sargassum polyceratium are extremely limited. The objective of the present study was to evaluate the antinociceptive activity of an ethanol extract of S. polyceratium and to isolate its components. Intraperitoneal treatment with ethanol extract of S. polyceratium reduced the number of acetic acid-induced writhes and the amount of time spent in paw-licking in the second phase of the formalin test. Ethanol extract of S. polyceratium also reduced the amount of time spent in paw-licking in the glutamate test; however, there was no difference in the reaction time in the hot plate test at any of the doses tested. The chemical components isolated from ethanol extract of S. polyceratium were identified using one- and two-dimensional spectroscopic methods such as infrared spectroscopy, mass spectrometry and 1H and 13C nuclear magnetic resonance spectroscopy. The analytical results were also compared with data obtained in the literature. The following porphyrin derivatives were isolated from S. polyceratium: 132-hydroxy-(132-R)-pheophytin-a, 132-hydroxy-(132-S)-pheophytin-a, pheophytin-a, and the steroid fucosterol. The present results indicate that the ethanol extract of S. polyceratium has antinociceptive activity. In addition, four new substances were isolated from the species evaluated.

Analgesic and Antiinflammatory Activities of the Essential Oil of the Unique Plant Zhumeria majdae

The analgesic and anti-inflammatory properties of Zhumeria majdae essential oil were investigated in mice and rats. The analgesic activity of the oil was assessed by acetic acid-induced writhing and Eddy's hot plate methods while the acute anti-inflammatory effect was investigated by inflammatory paw edema in rat. Z majdae oil significantly decreased the number of acetic acid-induced writhes in mice compared with animals that received vehicle only. Also it exhibited a central analgesic effect as evidenced by a significant increase in reaction time in the hot plate method. The oil also significantly reduced carrageenan induced paw edema in rats. The inhibitory activity of Z. majdae essential oil was found to be very close to that of the standard drug, diclofenac sodium (50 mg/kg). The studied oil was analyzed by GC and GC-MS and seventeen constituents were identified, representing 99.2% of the oil. The major components of the oil were characterized as linalool (63.4%) and camphor (27.5%), which might be responsible for these observed activities. The results suggest that Z. majdae essential oil possesses biologically active constituent(s) that have significant activity against acute inflammation and have central and peripheral antinociceptive effects which support the ethnomedicinal claims of the plant application in the management of pain and inflammation.

Analgesic and anti-inflammatory activities of Citrus aurantium L. blossoms essential oil (neroli): involvement of the nitric oxide/cyclic-guanosine monophosphate pathway.

The analgesic and anti-inflammatory properties of Citrus aurantium L. blossoms essential oil (neroli) were investigated in mice and rats. The analgesic activity of neroli was assessed by acetic acid-induced writhing and Eddy's hot plate methods, while acute and chronic anti-inflammatory effects were investigated by inflammatory paw edema in rat and the cotton pellet-induced granuloma tissue model, respectively. Mechanistic studies were conducted using L-nitro arginine methyl ester (L-NAME), an inhibitor of NO synthase. Neroli significantly decreased the number of acetic acid-induced writhes in mice compared to animals that received vehicle only. Also, it exhibited a central analgesic effect, as evidenced by a significant increase in reaction time in the hot plate method. The oil also significantly reduced carrageenan-induced paw edema in rats. The inhibitory activity of neroli (especially at 40mg/kg) was found to be very close to the standard drug, diclofenac sodium (50mg/kg). In cotton pellet-induced granuloma, neroli was effective regarding the transudate and granuloma formation amount. Neroli was analyzed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) and twenty-three constituents, representing 91.0% of the oil, were identified. The major components of neroli were characterized as linalool (28.5%), linalyl acetate (19.6%), nerolidol (9.1%), E,E-farnesol (9.1%), α-terpineol (4.9%), and limonene (4.6%), which might be responsible for these observed activities. The results suggest that neroli possesses biologically active constituent(s) that have significant activity against acute and especially chronic inflammation, and have central and peripheral antinociceptive effects which support the ethnomedicinal claims of the use of the plant in the management of pain and inflammation.

ANTINOCICEPTIVE AND ANTI-INFLAMMATORY EFFECTS OF HYDROALCOHOLIC EXTRACT OF LEAVES OF PIPTADENIA GONOACANTHA (MART.) MACBR. IN EXPERIMENTAL ANIMAL MODELS

This study aimed to evaluate the anti-inflammatory and antinociceptive effects of hydroalcoholic extract of P.gonoacantha leaves (EPG). The toxic effect of the EPG was tested against A.salina in order to determine a secure dose for subsequent assays. The antinociception was evaluated using the acetic acid-induced writhing and hot plate tests in Wistar rats. The anti-inflammatory effect of EPG was evaluated by carrageenan-induced paw edema tests in rats. The bioassay with A.salina showed low toxicity of EPG (LC50=1,508mg/L). Oral administration of EPG (50, 100 and 150mg/kg) significantly decreased the number of acetic acid-induced writhes, around 61.3%, 71.8% and 64.9% respectively. However, EPG failed to prolong the latency time in the hot plate test, suggesting that EPG predominantly inhibits peripheral pain mechanisms. The oral administration of EPG at doses of 50 and 100mg/kg significantly inhibited paw edema at 3rd h after the injection of the phlogistic agent by 34.5% and 37.5%, respectively. These data suggest that EPG has both antinociceptive and anti-inflammatory activities, and these effects may be attributed to inhibition of COX-2 and prostaglandin release.

Antinociceptive, anti-inflammatory and antipyretic activities of the leaf methanol extract of Ruta graveolens L. (Rutaceae) in mice and rats.

Ruta graveolens has been used to treat toothache, earache, rheumatism and fever with little scientific evidence corroborating these uses. The leaf methanol extract of Ruta graveolens was evaluated for antinociceptive activity using the acetic acid writhing and hot-plate tests in mice, also anti-inflammatory and antipyretic activities using the carrageenan-induced oedema and E. coli-induced pyrexia tests in rats, respectively. R. graveolens (100 mg/kg, i.p.), significantly reduced the number of acetic acid-induced writhes by 54 %. R. graveolens (400 mg/kg, i.p.), significantly delayed the reaction time in mice to thermal stimulation 15, 30, 45, and 60 min after treatment. Combined treatment of the lowest and sub-effective doses of the leaf methanol extract (25 mg/kg, i.p.), and indomethacin (10 mg/kg, i.p.) significantly reduced the number of acetic acid-induced writhes in mice. The leaf methanol extract of R. graveolens (50 - 400 mg/kg, i.p.), significantly reduced carrageenan-induced oedema over the 4 h period of testing. Combined treatment of the lowest doses of R. graveolens (25 mg/kg, i.p.) and indomethacin (2 mg/kg, i.p.) produced a significant reduction in carrageenan-induced oedema over the 4 h period of testing. R. graveolens (100 -400 mg/kg, i.p.) significantly reduced E. coli-induced pyrexia over the 5 h period of testing. Given together, the lowest dose of R. graveolens (25 mg/kg, i.p.) and pentoxifylline (10 mg/kg, i.p.) produced a significant reduction in pyrexia induced by E. coli (50 µg/kg, i.m.) over the 5 h period of measurement. The LD50 value obtained for R. graveolens was greater than 4000mg/kg (p.o), suggesting that the plant species may be safe in or nontoxic to mice. The data obtained indicate that R. graveolens has antinociceptive, anti-inflammatory and antipyretic activities, justifying the use of the plant species by traditional medicine practitioners in the management and treatment of pain, inflammation and fever.

Analgesic and hypnotic activities of Laghupanchamula: A preclinical study.

Background:In Ayurvedic classics, two types of Laghupanchamula -five plant roots (LP) have been mentioned containing four common plants viz. Kantakari, Brihati, Shalaparni, and Prinshniparni and the fifth plant is either Gokshura (LPG) or Eranda (LPE). LP has been documented to have Shothahara (anti-inflammatory), Shulanashka (analgesic), Jvarahara (antipyretic), and Rasayana (rejuvenator) activities.Aim:To evaluate the acute toxicity (in mice), analgesic and hypnotic activity (in rats) of 50% ethanolic extract of LPG (LPGE) and LPE (LPEE).Materials and Methods:LPEG and LPEE were prepared separately by using 50% ethanol following the standard procedures. A graded dose (250, 500 and 1000 mg/kg) response study for both LPEE and LPGE was carried out for analgesic activity against rat tail flick response which indicated 500 mg/kg as the optimal effective analgesic dose. Hence, 500 mg/kg dose of LPEE and LPGE was used for hot plate test and acetic acid induced writhing model in analgesic activity and for evaluation of hypnotic activity.Results:Both the extracts did not produce any acute toxicity in mice at single oral dose of 2.0 g/kg. Both LPGE and LPEE (250, 500, and 1000 mg/kg) showed dose-dependent elevation in pain threshold and peak analgesic effect at 60 min as evidenced by increased latency period in tail-flick method by 25.1-62.4% and 38.2-79.0% respectively. LPGE and LPEE (500 mg/kg) increased reaction time in hot-plate test at peak 60 min analgesic effect by 63.2 and 85.8% and reduction in the number of acetic acid-induced writhes by 55.9 and 65.8% respectively. Both potentiated pentobarbitone-induced hypnosis as indicated by increased duration of sleep in treated rats.Conclusion:The analgesic and hypnotic effects of LP formulations authenticate their uses in Ayurvedic system of Medicine for painful conditions.

Carvacryl acetate, a derivative of carvacrol, reduces nociceptive and inflammatory response in mice

AimsThe present study aimed to investigate the potential anti-inflammatory and anti-nociceptive effects of carvacryl acetate, a derivative of carvacrol, in mice. Main methodsThe anti-inflammatory activity was evaluated using various phlogistic agents that induce paw edema, peritonitis model, myeloperoxidase (MPO) activity, pro and anti-inflammatory cytokine levels. Evaluation of antinociceptive activity was conducted through acetic acid-induced writhing, hot plate test, formalin test, capsaicin and glutamate tests, as well as evaluation of motor performance on rotarod test. Key findingsPretreatment of mice with carvacryl acetate (75mg/kg) significantly reduced carrageenan-induced paw edema (P<0.05) when compared to vehicle-treated group. Likewise, carvacryl acetate (75mg/kg) strongly inhibited edema induced by histamine, serotonin, prostaglandin E2 and compound 48/80. In the peritonitis model, carvacryl acetate significantly decreased total and differential leukocyte counts, and reduced levels of myeloperoxidase and interleukin-1 beta (IL-1β) in the peritoneal exudate. The levels of IL-10, an anti-inflammatory cytokine, were enhanced by carvacryl acetate. Pretreatment with carvacryl acetate also decreased the number of acetic acid-induced writhing, increased the latency time of the animals on the hot plate and decreased paw licking time in the formalin, capsaicin and glutamate tests. The pretreatment with naloxone did not reverse the carvacryl acetate-mediated nociceptive effect. SignificanceIn conclusion, the current study demonstrated that carvacryl acetate exhibited anti-inflammatory activity in mice by reducing inflammatory mediators, neutrophil migration and cytokine concentration, and anti-nociceptive activity due to the involvement of capsaicin and glutamate pathways.

Peripheral antinociception and anti-edematogenic effect of a sulfated polysaccharide from Acanthophora muscoides

BackgroundSulfated polysaccharides from red marine algae have presented a variety of potentially therapeutic biological effects, however, their antinocicpetive and anti-inflammatory properties are not well understood. MethodsMale Swiss mice were pretreated with a sulfated polysaccharidic fraction obtained from the marine alga Acanthophora muscoides (AmII) (1, 3 or 9mg/kg, iv) 30min prior to either receiving an injection of 0.8% acetic acid or 1% formalin or prior to a thermal stimulus. AmII (1, 3 or 9mg/kg, sc) was evaluated on carrageenan-, dextran- bradykinin-, histamine- and serotonin-induced rat paw edema models. AmII (500 jig, sc) was also injected into the paw. Additionally, mice were treated with the total sulfated polysaccharides from A. muscoides (Am-TSP) (20mg/kg, ip) for 14 days. ResultsAmII reduced the number of acetic acid-induced writhes and licking time in the second phase of the formalin test, but it did not alter the response latency in the hot plate test, suggesting that its antinociceptive action occurs through a peripheral mechanism. AmII did not reduce carrageenan-induced paw edema and MPO activity. However, it reduced dextran-, histamine- and serotonin- induced paw edemas, but not bradykinin-induced edema, suggesting that histamine is the major target of AmII anti-edematogenic activity. AmII inj ected into the paw did not evoke local edema. Furthermore, Am-TSP induced no consistent signs of systemic damage, as revealed by body mass, organs wet weight and by biochemical, hematological and histopathological analyses. ConclusionAmII has important antinociceptive and anti-inflammatory properties and represents an important therapeutic agent warranting future studies.

Anti-nociceptive effect of vitexin mediated by the opioid system in mice

In the present study, we determined the potential anti-nociceptive activity of vitexin, a C-glycosylated flavone, by conducting some acute nociceptive tests in mice. Centrally mediated anti-nociceptive effect was evaluated by hot-plate and tail-clip tests, whereas peripherally mediated anti-nociception was assessed by acetic acid-induced writhing tests. Rota-rod test was performed to evaluate the probable effect of vitexin on the motor coordination of mice. Vitexin administered orally at doses of 10, 20, and 30mg/kg significantly increased the reaction times of animals in the hot-plate and tail-clip tests and reduced the number of acetic acid-induced writhes and stretches in writhing tests, which clearly indicated the presence of the anti-nociceptive effect. This effect disappeared by pretreatment with naloxone (a non-selective opioid receptor antagonist, 5.48mg/kg, i.p.), which indicated the involvement of opioid mechanisms in anti-nociception. We evaluated the contribution of mu, delta, and kappa subtypes of opioid receptors to the anti-nociceptive activity by using naloxonazine (7mg/kg, s.c.), naltrindole (0.99mg/kg, i.p.), and nor-binaltorphimine (1.03mg/kg, i.p.), respectively. Pretreatment using these antagonists reversed the anti-nociceptive effect of vitexin in all the nociceptive tests, which indicated that mu, delta, and kappa opioid receptors contributed to the anti-nociceptive effect of this flavonoid. Falling latencies of mice in the Rota-rod test did not change upon the administration of vitexin, which indicated that vitexin showed specific anti-nociceptive effect. To the best of our knowledge, this is the first study on centrally and peripherally mediated anti-nociceptive effect of vitexin via opioid-related mechanisms.