Beneficial effects of Anadenanthera colubrina (Vell.) Brenan extract on the inflammatory and nociceptive responses in rodent models

Ethnopharmacological relevance

Anadenanthera colubrina (Vell.) Brenan, popularly known as “angico”, is a plant that has been widely used in folk medicine due to its anti-inflammatory property. To evaluate the pharmacological activities of this plant, studies were performed on its antinociceptive and anti-inflammatory properties.

Materials and methods

The AE of Anadenanthera colubrina, made from the bark, was used in rodents via oral route (p.o.), at 100, 200, and 400 mg/kg in classical models of nociception (acetic acid-induced writhing and hot-plate test) and inflammation evoked by carrageenan (e.g., paw edema, peritonitis, and synovitis).

Results

The acetic acid-induced abdominal writhes in mice were significantly reduced (P<0.001) by oral treatment with the extract (100, 200, and 400 mg/kg), but the extract did not significantly increase the latency in the nociceptive hot-plate test. Anadenanthera colubrina aqueous extract reduced significantly the edema and, besides, diminished the mieloperoxidase activity (200 and 400 mg/kg, P<0.01). The carrageenan-induced peritonitis was significantly reduced (P<0.05) by the aqueous extract at 100, 200, and 400 mg/kg. The aqueous extract (200 mg/kg) reduces the synovial leukocyte infiltration on carrageenan-induced synovitis in rats (P<0.01), but failed to significantly affect joint swelling and impaired mobility.

Conclusions

We show for the first time that the anti-inflammatory and peripheral antinociceptive activities of Anadenanthera colubrina are consistent, at least in part, with the use of this plant in popular medicine practices.     

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.     

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-nociceptive and anti-inflammatory effects of Croton crassifolius ethanol extract

Ethnopharmacological relevance

Croton crassifolius has been used to treat snake bites, stomach ache, sternalgia, joint pain, as well as pharyngitis, jaundice, and rheumatoid arthritis in traditional Chinese medicine. However, there is no scientific evidence which supports the use in the literature.

Aim of the study

To investigate the anti-nociceptive and anti-inflammatory effects of ethanol extract of C. crassifolius.

Materials and methods

Anti-nociceptive actions of C. crassifolius were assessed in mice using the hot-plate test, acetic acid-induced writhing test, and formalin test. Anti-inflammatory effects of C. crassifolius were determined in three animal models: acetic acid-induced capillary permeability accentuation in mice, carrageenan-induced edema of the hind paw in rats, and cotton pellet-induced granuloma formation in rats.

Results

Ethanol extract of C. crassifolius showed no significant anti-nociceptive activity in the hot-plate test. However, extract at dosages of 45, 90 and 180 mg/kg significantly reduced acetic acid-induced writhing by 28.89% (P<0.05), 38.37% (P<0.05), and 56.53% (P<0.001), respectively. The extract also caused marked dose-related inhibition of formalin-induced pain in the second phase (P<0.05 for 45 mg/kg, P<0.001 for 90 and 180 mg/kg extract). C. crassifolius extract at dosages of 45, 90 and 180 mg/kg significantly reduced acetic acid-induced capillary permeability accentuation in mice by 26.18% (P<0.05), 65.70% (P<0.001), and 79.19% (P<0.001), and suppressed carrageenan-induced paw edema by 21.28% (P<0.05), 30.69% (P<0.01), and 49.17% (P<0.001) at 6 h after carrageenan injection, respectively. 180 mg/kg of the extract also showed significant activity against carrageenan-induced paw edema at 4 h. At 90 and 180 mg/kg, the extract inhibited cotton pellet-induced granuloma formation in rats.

Conclusions

These results collectively demonstrate that the ethanol extract of C. crassifolius possesses peripheral anti-nociceptive and anti-inflammatory effects, providing evidence to rationalize the traditional use of C. crassifolius for the treatment of pain and inflammation.     

Antinociceptive profile of the methanolic extract of Neorautanenia mitis root in rats and mice

The antinociceptive activity of the methanolic extract of Neorautenania mitis was studied in mice and rats. Five experimental models of nociception employed were: acetic acid-induced abdominal constriction and hot-plate test in mice, formalin-induced pain, analgesy-meter and Randall-Selitto tests in rats. The antinociceptive action of the extract was tested against naloxone in the hot-plate test in a bid to further elucidate probable mechanisms of antinociception. Results showed that the extract at doses of 5, 10 and 20 mg/kg body weight caused significant (P<0.05) dose-dependent antinociceptive activity in all the nociceptive models. Naloxone (2 mg/kg), significantly (P<0.05) antagonised the antinociceptive activity at the highest dose of the extract (20 mg). The study showed that the methanolic extract of Neorautanenia mitis possesses both peripherally and centrally mediated antinociceptive activity. The peripherally mediated action may be linked partly to lipoxygenases and/or cyclo-oxygenases, while the central anti-nociception is likely to be mediated via opioid receptors in the CNS.     

Inhibition of chemically induced inflammation and pain by orally and topically administered leaf extract of Manihot esculenta Crantz in rodents

The aqueous leaf extract of Manihot esculenta Crantz (MELE) is being used orally and topically in traditional African medicine for the treatment of inflammation and pain, and claimed to be safe. The anti-inflammatory effects of MELE (100-400mg/kg, p.o. or 1-4%, w/w in petroleum jelly, topically) were tested against carrageenan-induced paw oedema in rats as well as against xylene-induced ear oedema in mice. The analgesic effect of MELE (100-400mg/kg, p.o. or 1-4%, w/w in petroleum jelly, topically) was tested against acetic acid-induced (20mul, 0.6%, v/v in normal saline, i.p.) and acetylcholine-induced (8.3mg/kg, i.p.) mouse writhing models. At 100-400mg/kg, p.o. and 1-4% (w/w), topically, MELE produced significant inhibitions of carrageenan-induced rat paw oedema and xylene-induced ear swelling in mice. Effects produced by MELE were significantly higher than those produced by indomethacin (10mg/kg, s.c. or 1%, w/w in petroleum jelly) in the anti-inflammatory models. For the analgesic effect, MELE (100-400mg/kg, orally) and (1-4%, w/w, topically), like aspirin (100mg/kg, i.p.) exhibited significant (P<0.05) inhibition of acetic acid- and acetylcholine-induced mouse writhing tests, compared to untreated control. Effects produced by MELE were significantly lower than those produced by aspirin (100mg/kg, i.p.) in the analgesic models, except for the topically administered extract on acetylcholine-induced pain. Acute oral administration up to 10g/kg did not cause death within 14 days, but mortalities were produced in i.p. administered extract with LD(50) of 2.5+/-0.3g/kg. Based on these, the extract may contain orally safe, topically and orally effective anti-inflammatory and analgesic principles, which justify its use in traditional African medicine.     

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.     

Antinociceptive and anti-inflammatory effects of Tanacetum parthenium L. extract in mice and rats

Oral administration of the feverfew (Tanacetum parthenium) extract led to significant antinociceptive and anti-inflammatory effects against acetic acid-induced writhing in mice and carrageenan-induced paw edema in rats, respectively. These responses were dose-dependent (10, 20, 40 mg/kg, p.o.). Parthenolide (1, 2 mg/kg i.p.), the active constituent of the extract also produced antinociceptive and anti-inflammatory effects. Naloxone (1 mg/kg i.p.), an opiate antagonist, failed to reverse feverfew extract and parthenolide-induced antinociception. Feverfew extract in higher doses (40, 60 mg/kg p.o.) neither altered the locomotor activity nor potentiated the pentobarbitone-induced sleep time in mice. It also did not change the rectal temperature in rats. Feverfew extract exerted antinociceptive and anti-inflammatory effects without altering the normal behaviour of the animals.     

Anti-inflammatory and antinociceptive activities of Campomanesia adamantium

Ethnopharmacological relevance

Campomanesia species are used in folk medicine as anti-inflammatory, anti-rheumatic, anti-diarrheal and hypocholesterolemic.

Aim of the study

The present study investigated the in vivo anti-inflammatory and antinociceptive properties of ethyl acetate (AE) and aqueous (Aq) extracts from leaves of Campomanesia adamantium and in vitro anti-inflammatory activity of AE and its isolated flavonols, myricitrin and myricetin.

Materials and methods

The antinociceptive activity of AE and Aq was evaluated using acetic acid-induced writhing and formalin methods. The in vivo anti-inflammatory effect of AE and Aq was evaluated using carrageenan-induced paw oedema in mice. AE, myricitrin and myricetin were evaluated for their abilities to modulate the production of NO, TNF-α and IL-10 in LPS/IFN-γ stimulated J774.A1 macrophages.

Results

It was found that orally administrated AE and Aq (125 and 250 mg/kg) inhibited carrageenan-induced paw oedema in mice. AE (125 and 250 mg/kg) and Aq (125 mg/kg) reduced the time to licking at the second phase of the formalin method in vivo in mice. AE (250 mg/kg) and Aq (125 mg/kg) also reduced the number of writhes. AE, myricitrin and myricetin inhibited NO (320 μg/mL and 6.25–100 μM, respectively) and TNF-α production by macrophages (320 μg/mL for AE, 100 μM for myricitrin and 25–100 μM for myricetin). AE (160 and 320 μg/mL), myricitrin (50 and 100 μM) and myricetin (25–100 μM) increased IL-10 production by macrophages.

Conclusions

The ethyl acetate and aqueous extracts from Campomanesia adamantium showed antinociceptive and anti-inflammatory effects supporting the use of the plant in folk medicine. The results suggest that anti-oedematogenic effect promoted by aqueous extract involves several anti-inflammatory mechanisms of action. The antinociceptive effect shown by aqueous extract can be due to the modulation of release of inflammatory mediators involved in nociception. The anti-inflammatory effects of AE and of its isolated flavonols may be attributed to inhibition of pro-inflammatory cytokines production, TNF-α and NO and to the increased of IL-10 production.     

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.     

Antinociceptive and anti-inflammatory properties from the bulbs of Cipura paludosa Aubl

This study examined the antinociceptive and anti-inflammatory actions of Cipura paludosa Aubl. in several models of inflammatory pain in mice and rats. The ethanolic extract (EE) from Cipura paludosa (1-300mg/kg) given by i.p. and p.o. routes, 30 or 60min earlier, produced a dose-dependent inhibition of the acetic acid-induced pain and Evans blue leakage in mice with ID(50) values of 2.8 and 17.6mg/kg and 17.2 and 176.1mg/kg, respectively. The EE (10mg/kg, i.p.) also inhibited the allodynia (39+/-6%)- and oedema (97+/-6%)-induced by the intraplantar injection of CFA. In addition, the EE (1-30mg/kg, i.p.) inhibited both mechanical and thermal hyperalgesia induced by prostaglandin E(2), PMA and bradykinin in the rat paw, with ID(50) values of 7.3, 12.1 and 4.7 and 13.9, 18.9 and 1.5mg/kg, respectively. These data demonstrate that EE of Cipura paludosa elicited pronounced antinociceptive and anti-inflammatory actions against some models of inflammatory pain in mice and rats. The mechanism by which the extract produced antinociception still remains unclear, but a great part of this effect seems to be related to modulation of the release or action of pro-inflammatory mediators. Moreover, the antinociceptive action demonstrated in the present study supports, at least partly, the ethnomedical uses of this plant.     

Antinociceptive and anti-inflammatory activities of ethanolic extracts of Lychnophora species

Extracts from Lychnophora species are traditionally used in Brazil as anti-inflammatory, and to treat bruise, pain and rheumatism. The ethanolic extract of aerial parts of five species of Lychnophoras and one specie of Lychnophoriopsis were examined for the antinociceptive (hot-plate and writhing tests) and anti-inflammatory (carrageenan-induced paw oedema test) activity in mice, by oral and topical routes, respectively. In the hot-plate test, the Lychnophora pinaster (0.75 g/kg) and Lychnophora ericoides (1.50 g/kg) extracts significantly increased the time for licking of the paws. The species Lychnophora passerina, Lychnophoriopsis candelabrum and Lychnophora pinaster, using the dose of 0.75 g/kg, and Lychnophora ericoides and Lychnophora trichocarpha in both doses evaluated (0.75 and 1.50 g/kg) significantly reduced the number of writhes induced by acetic acid. The administration of Lychnophora pinaster and Lychnophora trichocarpha ointments, in both concentrations evaluated (5 and 10%, w/w), and Lychnophora passerina and Lychnophoriopsis candelabrum, in the concentration of 10%, significantly reduced the paw oedema measured 3 h after carrageenan administration, suggesting, for the first time, an anti-inflammatory activity upon topical administration of these species. The present work comparatively demonstrated the antinociceptive and anti-inflammatory activities of some Brazilian Lychnophoras.     

Antinociceptive and anti-inflammatory activities of Aquilaria sinensis (Lour.) Gilg. Leaves extract

AIM OF THE STUDY: The analgesic and anti-inflammatory activities of the ethanol extract of Aquilaria sinensis (Lour.) Gilg. Leaves were observed in various experimental models related to nociception and inflammation, so as to provide some evidence for its traditional use. MATERIALS AND METHODS: Acetic acid-induced writhing and a hot plate test in mice were used to evaluate its analgesic activity. On the other hand, its anti-inflammatory activity was observed in xylene or carrageenan-induced edema, carboxymethylcellulose sodium (CMC-Na)-induced leukocyte migration in mice and lipopolysaccharide (LPS)-induced nitric oxide (NO) release from mouse peritoneal macrophages in vitro. RESULTS: The ethanol extract significantly inhibited acetic acid-induced writhing after single oral administration 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 extract also remarkably lessened xylene-induced ear swelling, carrageenan-induced paw edema, and CMC-Na-induced leukocyte migration. Furthermore, the extract considerably reduced NO release from LPS-stimulated macrophages with IC50 of 80.4 mg/ml. CONCLUSION: These findings suggest that Aquilaria sinensis (Lour.) Gilg. Leaves extract present notable analgesic and anti-inflammatory activities, which support its folkloric use for some diseases related with painful and inflammatory conditions such as trauma etc.     

Analgesic and anti-inflammatory effects of Ligularia fischeri leaves in experimental animals

Aim of the study

The ethanol extract (LF) of Ligularia fischeri var. spiciformis (leaf) has been evaluated for antinociceptive and anti-inflammatory activities in mice.

Materials and Methods

Analgesic and anti-inflammatory activities were studied by measuring nociception induced by formalin, acetic acid and hot-plate, and inflammation induced by carrageenan, formalin, and arachidonic acid.

Results

The acute treatment of mice with LF at doses of 100 and 200 mg/kg, by oral administration, produced a significant antinociceptive effect in the acetic acid-induced writhing, formalin-induced pain licking and hot-plate-induced pain. Also, the LF significantly inhibited both carrageenan- and formalin-induced inflammation as well as arachidonic acid-induced ear edema in mice.

Conclusions

These inhibitions were statistically significant (P < 0.05). Thus, our investigation suggests a potential benefit of Ligularia fischeri in treating conditions associated with inflammatory pain.     

Anti-inflammatory effect of triterpene 3β, 6β, 16β-trihydroxylup-20(29)-ene obtained from Combretum leprosum Mart & Eich in mice

Ethnopharmacological relevance

The 3β, 6β, 16β-trihydroxylup-20(29)-ene (TTHL) is a pentacyclic triterpene obtained from a medicinal plant named Combretum leprosum. In folk medicine, this plant is used to treat several diseases associated with inflammation and pain. We previously demonstrated that TTHL presents a significant antinociceptive effect, suggesting the involvement of the glutamatergic system.

Aim of the study

This study was designed to investigate the effect of TTHL on nociception and vascular permeability induced by acetic acid. We also evaluated the effect of TTHL on carrageenan-induced peritonitis and the levels of cytokines (interleukin 1-β [IL-1β], tumor necrosis factor α [TNF-α] and interleukin 10 [IL-10]) on peritoneal fluid.

Materials and methods

TTHL was administered orally by intra-gastric gavage (i.g.) 60 min prior to experimentation. Abdominal contractions and vascular permeability were induced by an intraperitoneal (i.p.) injection of acetic acid (0.6%). We also investigated whether TTHL decreases carrageenan-induced peritonitis (750 μg/cavity) by measuring leukocyte migration and vascular permeability. In addition, we evaluated the effects of TTHL on TNF-α, IL-1β and IL-10 release induced by carrageenan on peritoneal fluid. The levels of these cytokines were measured by ELISA.

Results

TTHL (0.01–10 mg/kg) administered by intra-gastric (i.g.) gavage inhibited (69±3%) acetic acid-induced abdominal constrictions, with an ID₅₀ of 0.15 (0.03–0.8) mg/kg. TTHL (10 mg/kg) also reduced the leukocyte infiltration induced by acetic acid, with an inhibition of 59±9 but had no effect on abdominal vascular permeability. In addition, indomethacin (10 mg/kg, i.p.) reduced the nociceptive behavior (92±1%), total leukocyte migration (29±3%) and capillary permeability (71±3%) induced by acetic acid. While the glucocorticoid dexamethasone (2 mg/kg, s.c.) reduced partially but significantly the nociception (31±1%), besides to promote a marked reduction on total leukocyte migration (60±2%) to the peritoneal cavity caused by acetic acid. In a model of peritonitis induced by carrageenan, TTHL also reduced total leukocyte migration, mainly neutrophils (inhibition of 84±3% and 85±2% at 30 mg/kg and 100 mg/kg, respectively). Likewise, dexamethasone (0.5 mg/kg, i.p.) resulted in an inhibition of 93±3%. Nevertheless, carrageenan-induced abdominal vascular permeability was reduced by dexamethasone but was not altered by TTHL. Furthermore, dexamethasone and TTHL significantly reduced the TNF-α and IL-1β levels in peritoneal fluid, whereas the IL-10 levels were unchanged.

Conclusions

Altogether, our data confirm the antinociceptive effect of TTHL and demonstrate its effect in inflammatory animal models, providing novel data about this compound, which could be useful as an anti-inflammatory drug.     

Antinociceptive effects of Trigonella foenum-graecum leaves extract

There are some reports concerning the antinociceptive effects of the plant Trigonella foenum-graecum (TFG) in Iranian traditional medicine. Because of the side effects of nonsteroidal anti-inflammatory and antinociceptive drugs, and in search for more potent and less harmful compounds, we tried to study the antinocicptive effects of TFG leaves by using tail-flick and formalin tests. Intraperitoneal (i.p.) administration of 500 mg/kg of TFG extract and 100 and 300 mg/kg of sodium salicylate (SS), as a positive control, did not show any effect in the tail-flick test, but the 1000 and 2000 mg/kg of the extract produced significant increase in the tail-flick latency. SS (300 mg/kg, i.p.) induced antinociception in the second phase of the formalin test. TFG (500 mg/kg, i.p.) demonstrated antinociception only in the first phase, but 1000 and 2000 mg/kg, i.p. doses alleviated the pain in both phases. Preliminary LD₅₀ of the extract was very close to 4000 mg/kg, i.p. We conclude that: (1) the extract of TFG leaves produces antinociceptive effects through central and peripheral mechanisms; (2) the antinociceptive effects of 2000 mg/kg of the extract was more potent than 300 mg/kg of SS.     

Antinociceptive and anti-inflammatory effects of Thespesia populnea bark extract

The ethanolic extract of Thespesia populnea bark (TPE) was investigated for anti-inflammatory and analgesic activity at the doses (p.o.) of 100, 200 and 400mg/kg body weight. For evaluation of inflammation carrageenan-, histamine- and serotonin-induced paw edema served as acute models and formaldehyde-induced arthritis served as a chronic model in rats. The acetic acid-induced writhing response and formalin-induced paw licking time in the early and late phases of mice were used to assess analgesic activity. The higher doses of TPE (200 and 400mg/kg, p.o.) were inhibiting carrageenan, histamine and serotonin-induced paw edema as well as formaldehyde-induced arthritis successfully. In addition, TPE (200 and 400mg/kg, p.o.) significantly attenuated the writhing responses induced by an intraperitoneal injection of acetic acid and late phase of pain response induced by an subplantar injection of formalin in mice. Furthermore, our phytochemical studies indicated that the ethanolic extract of bark contains alkaloids, carbohydrates, protein, tannins, phenols, flavonoids, gums and mucilage, saponins and terpenes. From acute oral toxicity studies (OECD-423 guidelines), no mortality was observed even at highest dose of TPE (2000mg/kg, p.o.).     

Antinociceptive activity of ethanolic extract and isolated compounds of Urtica circularis

Ethnopharmacological relevance

Urtica circularis (Hicken) Sorarú is a medicinal plant commonly used in traditional medicine to relieve pain in inflammatory processes.

Aim of the study

In the present study, the in vivo antinociceptive effect of Urtica circularis ethanolic extract and its isolated compounds has been investigated.

Materials and methods

Antinociceptive activity was evaluated through writhing, formalin and hot plate tests in mice. The phytochemical analysis was performed.

Results

The extract produced significant inhibition on nociception induced by acetic acid (ED50: 72.2 mg/kg, i.p.) and formalin (ED50: 15.8 mg/kg, i.p.) administered intraperitoneally and also orally. Atropine diminished the activity of the extract in the acetic acid test. In this model, at dose of 10 mg/kg i.p., vitexin was the most active of the isolated compounds (inhibition of 91%), and chlorogenic acid, caffeic acid and vicenin-2 (6,8-di-C-glucosyl apigenin) produced an inhibition of 72%, 41% and 41%, respectively, whereas apigenin did not show any activity.

Conclusions

These results suggest that Urtica circularis extract produced antinociception possibly related to the presence of vitexin, chlorogenic, caffeic acid and vicenin-2. The activation of cholinergic systems seems to be involved in the mechanism of antinociception of the extract.     

Comparison of the anti-inflammatory and anti-nociceptive effects of three medicinal plants known as “Snow Lotus” herb in traditional Uighur and Tibetan medicines

Ethnopharmacological relevance

Saussurea involucrata (Kar. et Kir.) Sch.-Bip. (Compositae) has long been used under the herbal name “Snow Lotus” for the treatment of rheumatoid arthritis, stomachache and dysmenorrhea in Uighur folk medicine. In traditional Tibetan medicine, Saussurea laniceps Hand.-Mazz. and Saussurea medusa Maxim. have also been used under the name “Snow Lotus” and prescribed for the treatment of pain and inflammatory conditions.

Aim of the study

The present study evaluated the pharmacological effects of three species of “Snow Lotus” in experimental inflammation and pain models, and determined the chemical compounds that may correlate with their pharmacological activities.

Materials and methods

The anti-inflammatory activities of the three herbs were observed by using carrageenan-induced paw edema in rats and xylene-induced ear edema in mice. Investigations on the analgesic effects were conducted, including acetic acid-induced writhing and hot-plate test. An UPLC–MS method was developed to analyze the chemical composition of the three herbs and of plasma samples after herb administration.

Results

In rat paw edema model, the peak inhibitory effects of Saussurea laniceps and Saussurea involucrata (55.1% and 42.2%, respectively) were recorded with the dose of 400 mg/kg at 3 h post-carrageenan injection. In mouse ear edema model, oral administration of Saussurea laniceps, Saussurea involucrata and Saussurea medusa extract (400 mg/kg) resulted in a significant inhibition of ear edema by 40.9%, 33.3%, and 9.1%, respectively. In the writhing test, oral administration of Saussurea laniceps extract (100, 200 and 400 mg/kg) resulted in a significant inhibition of writhings by 13.5%, 22.3%, and 43.5%, respectively. In the hot-plate test, Saussurea laniceps extract significantly increased the latency of jumping response by 38.2% and 52.7% when treated orally at 200 and 400 mg/kg in mice, respectively. Flavonoids, coumarins and lignins were found to be present in plasma after administration of the extracts and may be the basis of the observed pharmacological effects.

Conclusion

The results clearly demonstrated that Saussurea laniceps was most effective; Saussurea involucrata exhibited a moderate potency, whereas Saussurea medusa possessed little effect against the experimental edema and pains. This study also supported discrimination among the three herbs when using them in folk medicine.     

Anti-ulcer, anti-inflammatory and antioxidant activities of the n-butanol fraction from Pteleopsis suberosa stem bark

Pteleopsis suberosa Engl. et Diels (Combretaceae) is a tree distributed in many African countries. The decoction from the stem bark is orally administered for the treatment of gastric ulcers in traditional medicine. Previous pharmacological studies reported the anti-ulcer activity of extracts from P. suberosa stem bark. In the present study, the anti-ulcer and anti-inflammatory effects of the n-butanol fraction (RBuOH) obtained from a methanol extract of P. suberosa bark were investigated on ethanol-induced gastric ulcers in rats and carrageenan-induced paw oedema in mice. Misoprostol (0.50 mg/kg, p.o.) and indomethacin (8.00 mg/kg, p.o.) were used as positive controls for anti-ulcer and anti-inflammatory activities, respectively. Results showed that RBuOH treatment significantly reduced the incidence of gastric lesions (50 mg/kg, P<0.05; 100 and 200 mg/kg, P<0.01) and restored the decreased levels of total sulfhydryl groups (T-SH) and non-protein sulfhydryl groups (NP-SH) (50, 100 mg/kg, P<0.05; 200 mg/kg, P<0.01) in the stomach homogenate. Moreover, RBuOH treatment attenuated MDA levels as index of lipid peroxidation in gastric mucosa. Administration of RBuOH at the same dosage (50, 100 and 200 mg/kg) reduced significantly (P<0.01) carrageenan-induced paw oedema in dose-dependent manner (from 42.81% to 87.81% inhibition, 5h after carrageenan injection). The anti-inflammatory effect of RBuOH at 200 mg/kg was comparable with that of indomethacin. Finally, RBuOH proved to possess elevated free radical scavenger capacity on 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay (IC(50) 23.48 microg/ml) which may contribute to the observed anti-ulcer and anti-inflammatory activities.