Antinociceptive and antiedematogenic effects of the aqueous extract of Hyptis pectinata leaves in experimental animals

The aqueous leaf extract of Hyptis pectinata (L.) Poit (Lamiaceae), popularly known in Brazil as "sambaicatá" or "canudinho", was tested for its antinociceptive effects using the abdominal writhing, hot plate and formalin test models, and for its aniedematogenic effects using the carrageenin and arachidonic acid-induced rat paw edema. The aqueous extract of Hyptis pectinata administered orally at doses of 100, 200 and 400 mg/kg had a significant antinociceptive effect in the test of acetic acid-induced abdominal writhing, with 43, 51 and 54% reduction of writhes, respectively, compared to the control. An increase in hot-plate latency of 47 and 37.5% was also observed in animals receiving doses of 200 and 400 mg/kg, p.o. when placed on a hot plate. In the formalin test, doses of 200 and 400 mg/kg, p.o. had no significant effect during the first phase of the test (0-5 min), while the dose of 200 mg/kg, p.o. reduced the nociceptive effect by 70% during the second phase (20-25 min). At the dose of 600 mg/kg, p.o., the aqueous extract inhibited carrageenin-induced rat paw edema by 34.1%, and the dose of 300 mg/kg administered intraperitoneally inhibited the rat paw edema induced by subplantar injection of arachidonic acid by 32.8%. These results suggest that the aqueous extract from the Hyptis pectinata leaves produces antiedematogenic and antinociceptive effects. The antinocipetion observed with the hot-plate test probably involves the participation of the opioid system.     

Evaluation of the analgesic effect of alkaloid extract of Peganum harmala L.: possible mechanisms involved

The seeds of Peganum harmala L. (Pgh) (Zygophyllaceae) have been used in Moroccan traditional medicine for treatment of a various diseases and to relieve dolorous process. The major objective of this paper was to investigate the mechanism of the analgesia induced by alkaloid extract of Peganum harmala. In the present work, the antinociceptive action was assayed in several experimental models in mice: writhing, formalin, and hot plate tests. The alkaloid extract (12.5 and 25mg/kg) and in a dose-dependent manner significantly reduced the nociception by acetic acid intraperitoneal injection (p<0.001). In the formalin test, the extract also significantly reduced the painful stimulus in both phases of the test (p<0.001). Treatment with the extract when given by (i.p. or i.c.v.) or with morphine (10mg/kg, i.p.) produced a significant increase of the reaction time in hot plate test. These result showed that the alkaloid extract of Pgh contains active analgesic principles acting both centrally and peripherally. Furthermore, this antinociceptive effect has been avoided by naloxone at a dose of 1mg/kg in the first phase of formalin and hot plate tests indicating that this extract act partly through an opioid-mediated mechanism. In conclusion, the alkaloid extract of Peganum harmala seems to have both central and peripheral antinociceptive activities which may be mediated by opioid receptors.     

Antinociceptive activity of the methanolic extract of Kaempferia galanga Linn. in experimental animals

Kaempferia galanga Linn. (Zingiberaceae) presents many chemical constituents of the volatile oil extracted from the rhizome. The rhizome of Kaempferia galanga is used by people in many regions for relieving toothache, abdominal pain, muscular swelling and rheumatism. In this study we investigated the antinociceptive activity in mice and rats using acetic acid-induced writhing, formalin, hot plate and tail-flick tests. The extract at test doses of 50, 100 and 200 mg/kg, p.o. clearly demonstrated antinociceptive activity in all tests. This activity was dose- and time-dependent. The extract administered at 200 mg/kg, p.o. had a stronger antinociceptive effect than aspirin (100 mg/kg, p.o.) but less than morphine (5 mg/kg, s.c.). Naloxone (2 mg/kg, i.p.) abolished the antinociceptive action of both morphine (5 mg/kg, s.c.) and the extract (200 mg/kg, p.o.) in a similar manner. In conclusion, the methanol extract of Kaempferia galanga markedly demonstrated the antinociceptive action in experimental animals. The antinociceptive mechanisms appear to be both peripherally and centrally mediated actions and the opioid receptors are probably involved. Therefore, our studies support the use in traditional medicine of Kaempferia galanga against pain caused by various disorders.     

Evaluation of the antinociceptive activity of extracts of Sonchus oleraceus L. in mice

Ethnopharmacological relevance

Sonchus oleraceus L. has been used to relieve pain in Brazilian folk medicine.

Aim of the study

Sonchus oleraceus L. has been used to relieve pain in Brazilian folk medicine. This study was conducted to establish the antinociceptive properties of hydroethanolic and dichloromethane extracts from aerial parts of Sonchus oleraceus in mice using chemical and thermal models of nociception.

Materials and methods

The formalin, hot plate, and tail immersion tests as well as acetic acid-induced writhing were used to investigate the antinociceptive activity in mice.

Results

Given orally, the extracts at test doses of 30–300 mg/kg, produced significant inhibitions on chemical nociception induced by intraperitoneal acetic acid and subplantar formalin since decreased the number of writhing episodes and the time licking. Treatment with the extracts in the same doses produced a significant increase of the reaction time in tail immersion and in the hot plate test. The extracts administered at 300 mg/kg, p.o. had a stronger antinociceptive effect than indomethacin (5 mg/kg, p.o.) and morphine (10 mg/kg, p.o.).

Conclusion

The extracts of Sonchus oleraceus markedly demonstrated antinociceptive action in mice, which supports previous claims of its traditional use.     

Antinociceptive and antiinflammatory activities of pine (Pinus densiflora) pollen extract

The study aimed to evaluate the antinociceptive and antiinflammatory activity of pine (Pinus densiflora) pollen in mice. The antinociceptive activity was determined using acetic acid-induced abdominal constriction and formalin-induced licking, and the hot plate test. Antiinflammatory effects were evaluated using carrageenan- and formalin-induced paw edema, and arachidonic acid-induced ear edema in mice. The ethanol extract of pine pollen (100 and 200 mg/kg, p.o.) produced a significant inhibition of both phases of the formalin pain test in mice, a reduction in mouse writhing induced by acetic acid and an elevation of the pain threshold in the hot plate test in mice. The pine pollen extract also produced a significant inhibition of carrageenan- and formalin-induced paw edema as well as arachidonic acid-induced ear edema in mice. The inhibitions were similar to those produced by aminopyrine and indomethacin, p.o. The different polyphenols found in pine pollen could account for the antinociceptive and antiinflammatory actions. The results obtained indicate that the extract possesses analgesic and antiinflammatory effects.     

Investigations on the antinociceptive effect of Psidium guajava leaf essential oil and its major constituents

The antinociceptive effect of leaf essential oil from Psidium guajava and its major constituents, β-caryophyllene and α-pinene was assessed using chemical (formalin and acetic acid) and thermal (hot-plate) nociceptive tests in adult male albino mice. Oral administration of 100, 200 and 400 mg/kg of essential oil produced a significant antinociceptive effect in the formalin test and at 200 and 400 mg/kg in the acetic acid- induced writhing test. Of the major components only α-pinene, but not the β-caryophyllene, demonstrated significant antinociception in the formalin test. Neither the essential oil nor the major components could exert any significant effect in the hot-plate test. Pretreatment of mice with caffeine (20 mg/kg, i.p.), significantly inhibited the antinociceptive effect of essential oil in the formalin test. Naloxone (1 mg/kg, s.c.), the opioid antagonist, however, failed to antagonize it. These results suggest that the antinociceptive effect of P. guajava essential oil is probably mediated by endogenously released adenosine. © 1998 John Wiley & Sons, Ltd.     

Antinociceptive and anti-inflammatory effects of Satureja hortensis L. extracts and essential oil

Satureja hortensis L. (Lamiaceae) is a medicinal plant used in Iranian folk medicine as muscle and bone pain reliever. In the present study, hydroalcoholic extract, polyphenolic fraction and essential oil of the aerial parts of the herb were prepared and evaluated for the analgesic activity using light tail flick, formalin and acetic acid-induced writhing in mice. Also, the anti-inflammatory effects of the above-mentioned preparations were assessed using carrageenan-induced paw edema in rats. Results showed that in the light tail flick test neither the essential oil nor the extracts could exert any significant effect. The hydroalcoholic extract (2000 mg/kg, p.o.) and the essential oil (200 mg/kg, p.o.) inhibited the mice writhing responses caused by acetic acid. In formalin test, hydroalcoholic extract (500-2000 mg/kg, p.o.), polyphenolic fraction (250-1000 mg/kg, p.o.) and the essential oil (50-200 mg/kg, p.o.) showed analgesic activity and pretreatment with naloxone (1 mg/kg, i.p.) or caffeine (20 mg/kg, i.p.) failed to reverse this antinociceptive activity. Polyphenolic fraction (1000 mg/kg, p.o.) and the essential oil (200 mg/kg) reduced edema caused by carrageenan. These results suggest that S. hortensis L. has antinociceptive and anti-inflammatory effects and probably mechanism(s) other than involvement of opioid and adenosine receptors mediate(s) the antinociception.     

Anti-inflammatory,analgesic activity and acute toxicity of Glaucium grandiflorum extract

The species of Glaucium have been used in Iranian herbal medicine as laxative, hypnotic, antidiabetic agents and also in the treatment of dermatitis. The anti-inflammatory and analgesic effects of the aerial parts of Glaucium grandiflorum Boiss & Huet (Papaveraceae), a native plant of Iran, were studied using carrageenan induced edema, formalin and hot plate tests. The G. grandiflorum extract at the dose of 200 mg/kg had more edema inhibition than indomethacin at the doses of 10 (P<0.01) and 8 mg/kg (P<0.001) in the carrageenan test. The ED₅₀ (i.p.) in the edema induced by carrageenan was 13.59 mg/kg. In formalin test, the extract (60–90 mg/kg, i.p.) caused graded inhibition of both phases of formalin-induced pain. In hot plate test, the i.p. administration of the extract at the doses of 60, 70, 80 and 90 mg/kg significantly raised the pain threshold at a observation time of 45 min in comparison with control (P<0.001). The extract, at the antinociceptive doses, did not affect motor coordination of animals when assessed in the rotarod model. The 72 h acute LD₅₀ value of this extract after i.p. administration in mice was 797.94 mg/kg.     

Antinociceptive effect of Lecythis pisonis Camb. (Lecythidaceae) in models of acute pain in mice

Ethnopharmacological relevance

Lecythis pisonis Camb., also known in Brazil as sapucaia, is used in folk medicine against pruritus, muscle pain and gastric ulcer.

Aim of the study

To investigate the antinociceptive effect of ethanol extract from Lecythis pisonis leaves (LPEE), fractions (hexane-LPHF, ether-LPEF and ethyl acetate-LPEAF) and mixture of triterpenes [ursolic and oleanolic acids (MT)] in mice.

Materials and methods

LPEE and LPEF were evaluated on the acetic acid induced writhings and formalin, capsaicin and glutamate tests. In addition, MT was investigated on the writhings induced by acetic acid, capsaicin and glutamate tests. In the study of some possible mechanisms involved on the antinociceptive effect of LPEF, it was investigated the participation of opioid system, K⁺_ATP channels and l-arginine-nitric oxide pathway.

Results

LPEE (12.5 and 25 mg/kg, p.o.), LPEF and MT (6.25, 12.5 and 25 mg/kg, p.o.) reduced the writhings in comparison to saline. LPEE (100 mg/kg, p.o.) and LPEF (50 mg/kg, p.o.) were effective in inhibiting both phases of formalin test. In capsaicin test, LPEE (100 and 200 mg/kg, p.o.), LPEF (12.5–50 mg/kg, p.o) and MT (6.25–25 mg/kg, p.o.) showed a significant antinociceptive effect compared to the control. LPEE (25 and 50 mg/kg, p.o.), LPEF (50 and 100 mg/kg, p.o.) and MT (12.5 and 25 mg/kg, p.o.) reduced the glutamate-evoked nociceptive response. Treatment with naloxone, l-arginine and glibenclamide reversed the effect of LPEF in glutamate test.

Conclusions

These results indicate the antinociceptive effect of Lecythis pisonis leaves and suggest that this effect may be related to opioid pathway, K⁺_ATP channels, and l-arginine-nitric oxide modulation. Furthermore, these data support the ethnomedical use of this plant.     

The antinociceptive and anti-inflammatory activities of Piptadenia stipulacea Benth. (Fabaceae)

Aim

In this study, we attempted to identify the possible antinociceptive and anti-inflammatory actions of the aqueous phase, the ethyl acetate phase and one unknown flavonoid obtained from aerial parts of Piptadenia stipulacea, known in Brazil as “jurema-branca”, “carcará” and “rasga-beiço”.

Materials and methods

Aerial parts of Piptadenia stipulacea were used and after fractionation, the flavonoid FGAL was obtained. Experiments were conducted on Swiss mice using the acetic acid-induced writhing test, the hot plate test, the formalin-induced pain test and zymosan A-induced peritonitis test.

Results

The aqueous and ethyl acetate phases (p.o., 100 mg/kg); and the flavonoid FGAL (p.o. and i.p. at 100 μmol/kg), reduced the nociception produced by acetic acid, by 49.92%, 54.62%, 38.97% and 64.79%, respectively. In vivo inhibition of nociception by the ethyl acetate phase (100 mg/kg, p.o.) in the hot plate test was favorable, indicating that this fraction exhibited central activity. The ethyl acetate phase (100 mg/kg, p.o.) reduced the formalin effects in both phases by 28.51% and 55.72%, respectively. Treatment with the aqueous phase (100 mg/kg, p.o.) and FGAL (100 μmol/kg, i.p.) only protected the second phase by 69.76% and 68.78%, respectively. In addition, it was observed in the zymosan A-induced peritonitis test that the aqueous phase, the ethyl acetate phase and the FGAL exhibited anti-inflammatory activity, reducing significantly the number of recruit cells by 35.84%, 37.70% and FGAL (1), respectively.

Conclusions

These data demonstrate that the FGAL elicits pronounced antinociceptive activity against several pain models. The actions of this flavonoid probably are due to antioxidative properties. However, pharmacological and chemical studies are continuing in order to characterize the mechanism(s) responsible for this antinociceptive action and also to identify other active substances present in Piptadenia stipulacea.     

Analgesic Effect of the Herbal Medicine Catuama in Thermal and Chemical Models of Nociception in Mice

The antinociceptive effect of the herbal medicine Catuama and the hydroalcoholic extract (HE) of each plant present in this extract were investigated in chemical and thermal models of nociception in mice. The extract of Catuama (200 mg/kg, p.o.) caused time-dependent and long-lasting antinociception against acetic acid-induced writhing, formalin and capsaicin-induced licking and also in the tail-flick and hot-plate assays. Its maximal analgesic effect was reached 6 h after its oral administration and this effect lasted for at least 12 h. When given 6 h prior to testing (100 and 200 mg/kg, p.o.), the extract elicited dose-related antinociception, but at 400 mg/kg, its analgesic effect was greatly reduced. The antinociception caused by the extract of Catauma, like those produced by morphine, was largely antagonized by naloxone. The daily administration of the extract (200 mg/kg, p.o. for 4 days) or morphine (5 mg/kg, s.c. for 4 days) produced progressive tolerance, an effect which was reverted by naloxone (5 mg/kg, i.p.). In addition, the Catuama extract showed cross-tolerance with morphine. The Catuama antinociception was not due to its non-specific effects such as muscle relaxation or sedation of animals, nor was it secondary to its antiinflammatory property. When analysed separately the hydroalcoholic extract (HE) obtained from Trichilia catigua, Paullinia cupana, Ptychopelatum olacoids, Zinziber officinalis (200 mg/kg, p.o., 6 h prior) all inhibited acetic acid-induced pain (82%±2%; 66%±2%; 42%±2% and 30%±4% of inhibition, respectively ( p <0.01). In the formalin test the HE of P. olacoids; P. cupana; T. catigua and to a lesser extent, Z. officinalis (200 mg/kg, p.o., 6 h prior) also inhibited both phases of formalin-induced pain ( p <0.01). Thus, antinociception caused by the Catuama extract seems to be dependent on the interaction of the several active principles present in these plants. The mechanisms underlying the antinociception caused by extract of herbal medicine Catuama is still not completely understood, but a significant number of these effects are related to its interaction with the naloxone sensitive opioid system. Together, the results indicate that the herbal medicine Catuama may constitute a useful therapeutic agent for the treatment of clinical pain. © 1997 by John Wiley & Sons, Ltd.     

Evaluation of antinociceptive,antinflammatory activities and phytochemical analysis of aerial parts of Urtica urens L.

The antinociceptive and antiinflammatory activities of the ethanol extract of the aerial part of Urtica urens were determined by experimental animal models. U. urens extract was found to possess significant antinociceptive activity in chemically induced mouse pain models (ED₅₀ 39.3 mg/kg: 17.2–74.5 mg/kg) in the writhing test and 62.8% inhibition of the licking time in the late phase of the formalin test at a dose of 500 mg/kg p.o. and antiinflammatory activity on carrageenan‐induced rat hind paw edema (41.5% inhibition at a dose of 300 mg/kg i.p.). The extract displayed activity neither in the thermal model of pain nor in the topical inflammation model. The major component of the extract was determined as chlorogenic acid (670 mg/1000 g dry weight) and could be partly responsible for this activity. Copyright © 2010 John Wiley & Sons, Ltd.     

Study on the antinociceptive effects of Thymus broussonetii Boiss extracts in mice and rats

In Morocco, Thymus broussonetii is widely used in folk medicine for the treatment of a variety of diseases including gastroenteric and bronchopulmonary disorders and to relieve dolorous process. The antinociceptive effect of the aqueous, butanolic and ethyl acetate extracts of this species was examined in rats and mice using chemical and thermal models. The results obtained showed that aqueous and butanolic extracts exerted an antinociceptive activity in the two phases of formalin (50-300 mg/kg), tail immersion and writhing tests. Whereas, the ethyl acetate extract reduced the nociceptive response only in the second phase of formalin (100-300 mg/kg) and writhing tests. The aqueous extract, which is the most effective, contains active analgesic principles acting both centrally and peripherally. Furthermore, this antinociceptive effect has been avoided by naloxone at a dose of 1mg/kg in the first phase of formalin and hot plate tests indicating that this extract acts partly through an opioid-mediated mechanism. The present results demonstrated that Thymus broussonetii contains active constituents which possess antinociceptive activity justifying its popular use to relieve some pains.     

The juice of fresh leaves of Boerhaavia diffusa L. (Nyctaginaceae) markedly reduces pain in mice

The decoction or juice of leaves of Boerhaavia diffusa L. (Nyctaginaceae) is used in Martinican folk medicine for its analgesic and anti-inflammatory properties. In the present investigation we studied the acute oral (p.o.) toxicity of a crude extract obtained from a lyophilized decoction (DE) and from the juice (JE) of fresh leaves. We observed no signs of toxicity up to the dose of 5000 mg/kg (p.o.) in mice. At the dose of 1000 mg/kg, neither extract altered sleeping time evoked by the administration of pentobarbital sodium (i.p.). The DE and JE of B. diffusa were assessed in standard rodent models of algesia and inflammation. We investigated the antinociceptive effect of DE and JE in chemical (acetic acid) and thermal (hot plate) models of hyperalgesia in mice. Dipyrone sodium (200 mg/kg), JE (1000 mg/kg) and DE at the same dose (p.o.), produced a significant inhibition of acetic acid-induced abdominal writhing in mice (100, 50 and 47% inhibition, respectively) when compared with the negative control (P<0.001). In the hot-plate test in mice, morphine and JE produced a significant increase in latency during the observation time. The DE, however, only raised the pain thresholds during the first period (30 min) of observation (P<0.05). The extracts of B. diffusa were also investigated for their anti-edematogenic effect on carrageenan-induced edema in mice. However, neither extract inhibited the paw edema induced in mice (P>0.05). In the acetic acid-induced abdominal writhing in mice, pre-treatment of the animals with naloxone (5 mg/kg, i.p.) significantly reversed the analgesic effect of morphine and JE but not that of DE. These data show that the active antinociceptive principle of B. diffusa is present mainly in the juice of fresh leaves and has a significant antinociceptive effect when assessed in these pain models. The mechanism underlying this analgesic effect of fresh leaves of B. diffusa remains unknown, but seems to be related to interaction with the opioid system.     

Antinociceptive effect of the aqueous extract of Balbisia calycina.

The aqueous extract from the aerial parts of Balbisia calycina (Gris.) A.T. Hunziker et Ariza (Ledocarpaceae), was evaluated for antinociceptive activity using the abdominal constriction, hot plate and formalin tests. The extract was administered orally to male mice at doses of 200, 400 and 800 mg/kg. A dose-dependent antinociceptive effect of the extract was obtained with the abdominal constriction test at doses of 400 and 800 mg/kg. This antinociceptive effect was not reversed by pretreatment with naloxone. No significant response was obtained with the hot plate test. With the formalin test doses of 400 and 800 mg/kg had no significant effect during the first phase of the test (0-5 min), while with the dose of 800 mg/kg, a significant inhibition during the second phase (15-30 min) was observed. The phytochemical investigation of the aqueous extract of B. calycina revealed the presence of the flavonoids luteolin, avicularin and hyperoside. The possible involvement of these flavonoids (specially luteolin) in the antinociceptive action is discussed.     

Antinociceptive effect and toxicological study of the aqueous bark extract of Barringtonia racemosa on rats

Barringtonia racemosa Linn. (Family Lecythidaceae) possess several bioactivities and is used in traditional medicine of Sri Lanka, but its analgesic potential has not been investigated so far. The aim of this study was therefore to examine the antinociceptive potential of an aqueous bark extract (500, 750, 1000 or 1500 mg/kg) of B. racemosa in male rats using three models of nociception (tail flick, hot plate and formalin tests). The results showed that the extract has antinociceptive activity (when evaluated in hot plate and formalin test but not in tail flick test) without producing unwanted side effects or toxicity. Further, the extract did not alter fertility, gestational length, peri- and neonatal development and appears to be non-teratogenic. The antinociceptive effect was mediated mainly via opioid mechanisms. Such inhibition of pain could arise from phenolic and steroidal constituents as was shown to be present in the extract.     

Characterisation of the anti-inflammatory and antinociceptive activities of the Hyptis pectinata (L.) Poit essential oil

Aim of the study

Hyptis pectinata Poit (Lamiaceae) is grown in the northeastern regions of Brazil and is popularly known as “sambacaitá” or “canudinho”. It is extensively used in folk medicine to treat inflammatory conditions, bacterial infections, pain, and cancer.

Materials and methods

Hyptis pectinata essential oil (EO, 10, 30, and 100 mg/kg, p.o.) and the reference drugs morphine (5 mg/kg, p.o.) and acetylsalicylic acid (ASA, 200 mg/kg, p.o.) were evaluated using models for analgesia (acetic acid-induced contortions and hot plate) or inflammation (formalin-induced licking response and the subcutaneous air-pouch model). To elucidate the EO's mechanism of action, animals were pre-treated with the opioid receptor antagonist naloxone (1 mg/kg, i.p.), the cholinergic antagonist atropine (1 mg/kg, i.p.), or l-nitro arginine methyl ester (l-NAME, 3 mg/kg, i.p.) 30 min prior to the oral administration of the EO.

Results

The EO significantly inhibited the number of writhings and the time the animals spent licking their formalin-injected paws (second phase). The EO, at doses of 30 and 100 mg/kg, increased baseline measurements and area under the curve measurements in the hot plate model, respectively. The administration of naloxone reversed the antinociceptive effect of the EO in the hot plate model. l-NAME significantly reversed the effects of the EO in the contortions and hot plate models. Atropine completely reversed the antinociceptive activity of the EO in all models. Additionally, the EO inhibited the inflammatory process induced by subcutaneous carrageenan injection by reducing cell migration, exudate volume, protein concentration, and inflammatory mediators (nitric oxide, prostaglandin E2, IL-6, and TNF-α) produced in the pouch.

Conclusions

Our results indicate that the Hyptis pectinata essential oil exhibits antinociceptive effects, likely mediated by opioid and cholinergic receptors, and anti-inflammatory activity through the inhibition of nitric oxide and PGE2 production.     

Antinociceptive and anti-inflammatory effects of Elaeagnus angustifolia fruit extract

In this study, probable antinociceptive and anti-inflammatory effects of Elaeagnus angustifolia fruit components, were evaluated. For evaluation of antinociceptive effects, the chronic (formalin test) and acute (tail-flick) pain models of rats were used. For the anti-inflammatory effects, the paw inflammation model was used through subcutaneous injection of 5% formalin to the paw of male rats. Water extracts of the fruit and its components in the single dose were assessed through comparison with the antinociceptive and anti-inflammatory effects of sodium salicylate (SS) as a positive control. Administration of 300 mg/kg of SS (i.p.) had no effect on tail flick latency, while 1000 mg/kg of total (i.p. and p.o.) and endocarp (i.p.) extract, increased this latency (P<0.01, P<0.001, respectively), which was not reversed by naloxone (2 mg/kg). In the formalin test, SS (300 mg/kg, i.p.) and the extract (1000 mg/kg, p.o. ) alleviated the animals nociception in the second phase, while in the first phase they were not effective. The total and endocarp extracts (1000 mg/kg, i.p.) showed a significant effect on both phases (P<0.01, P<0.001, respectively) which was also not reversed by naloxone (2 mg/kg, i.p.). In the acute anti-inflammatory test, the total extract and the aqueous extract of individual fruit components showed a significant effect (P<0.001). This anti-inflammatory effect was not significant compared with the anti-inflammatory effect of SS. Because of the extract effect on the tail-flick latency and both phases of the formalin test, the site of its analgesic action is probably central, and the mechanism of antinociceptive action of the extract are not related to the opioid system. Our phytochemical studies indicated that aqueous extract of E. angustifolia fruit contains flavonoids, terpenoids and cardiac glycosides.     

Effects of paeoniflorin on the formalin-induced nociceptive behaviour in mice

In this study, we attempted to identify the mechanisms of paeoniflorin on antinociceptive effects in mice. Paeoniflorin (48, 96, 240, 480 microg, i.c.v.) showed dose-related antinociception both on the early and late phases of formalin test in mice. Moreover, paeoniflorin (48 microg, i.c.v.) could potentiate the antinociception of morphrine (0.5, 1.0 mg/kg, s.c.) in the formalin test. However, the antinociceptive effects of paeoniflorin were not potentiated by L-arginine (600 mg/kg, i.p.) or antagonized by beta-funaltrexamine (beta-FNA) (10 microg, i.c.v.), ICI-174,864 (1 microg, i.c.v.) and ryanodine (10 ng, i.c.v.) on both the early and late phases of formalin test. L-NAME (75 mg/kg, i.p.) could reverse the effect of paeoniflorin on the late phase of formalin test. Naloxone (1 mg/kg, i.p.) and nor-binaltorphimine (nor-BNI) (1 microg, i.c.v.) could block the paeoniflorin-induced antinociception on the early phase of formalin test. These results suggested that the central antinociceptive effects of paeoniflorin on formalin test in mice were mediated by the activation of kappa-opioid receptor and not related to the increase of intracellular calcium.     

Antinociceptive effect of the aqueous extract obtained from roots of Physalis angulata L. on mice

In this study, we attempted to identify the possible antinociceptive action of aqueous extract (AE) obtained from roots of Physalis angulata, known in Brazil as "Camapu", used to treat various pain-related physiological conditions. The AE of Physalis angulata (10-30 mg/kg) given by i.p. or p.o. route, 0.5 and 1h prior, produced significant inhibition of abdominal constrictions caused by acetic acid, with ID(50) values of 18.5 (17.4-19.8) and 21.5 (18.9-24.4)mg/kg and inhibitions of 83+/-8 and 66+/-5%, respectively. The AE (10-60 mg/kg, i.p.) also caused significant inhibition of the late-phase of formalin-induced pain, with an ID(50) value of 20.8 (18.4-23.4)mg/kg and inhibition of 100%. Treatment of mice with AE (60 mg/kg, i.p.) or with morphine (10mg/kg, i.p.) produced a significant increase of the reaction time in the hot-plate test. These results demonstrate, for the first time, that the AE of Physalis angulata produce marked antinociception against the acetic acid-induced visceral pain and inflammatory pain responses induced by formalin in mice. The mechanism by which the AE produces antinociception still remains unclear. However, pharmacological and chemical studies are continuing in order to characterize the mechanism(s) responsible for the antinociceptive action and also to identify the active principles present in Physalis angulata. Moreover, the antinociceptive action demonstrated in the present study supports, at least partly, the ethnomedical uses of this plant.