Samanea tubulosa Benth. (Fabaceae): Antinociceptive effect on acute pain in mice: K+ATP channel and opioid activity.

Samanea tubulosa Benth. it has been widely used in traditional medicine to treat inflammatory processes. The present study aimed to investigate the antinociceptive effect and mechanism of action of the fractions obtained from the Samanea tubulosa pods in mice. The antinociceptive activity was evaluated in formalin, capsaicin and glutamate tests and the. The possible mechanisms of action involved in the antinociceptive effect of the hexane and ethyl acetate fraction in the opioid system, also the the K + ATP channels and the L-arigine pathways of nitric oxide were evaluated. The chemical characterization analysis revealed in the hexane fraction the presence of triterpenes such as lupenone and lupeol. In the glutamate test, the hexane and ethyl acetate fractions showed antinociceptive activity at the dose of 12.5 and 25 mg kg-1. The antinociception produced by the hexane and ethyl acetate fractions was significantly reversed by naloxone, indicating that the fractions act through the opioid pathway. Antinociceptive response of the ethyl acetate fraction was blocked by glibenclamide, indicating that this fraction acts via the K + ATP channels activation. It is concluded that the fractions under study exert antinociceptive activity possibly related to the opioid route and through K+ ATP channels activation.

Endorectal formalin instillation or argon plasma coagulation for hemorrhagic radiation proctopathy therapy: a prospective and randomized clinical trial.

BACKGROUND AND AIMS: Radiotherapy may cause hemorrhagic radiation proctopathy (HRP). For conservative treatment of refractory HRP, argon plasma coagulation (APC) is the first-choice therapy. Endorectal formalin instillation (EFI), in turn, is an attractive treatment option because of its satisfactory results, great availability, and low cost. Nevertheless, comparative studies between these procedures are rather scarce. This study aims to make a prospective and randomized comparison of the outcomes in 2 HRP patient groups treated with either APC or EFI. METHODS: Twenty-seven patients (11 women), with a mean age of 67 years (range, 36-83), were randomized to receive either APC (n = 14) or EFI (n = 13). On completion of the treatment, comparisons were made in relation to the baseline for each patient and between groups for endoscopic findings according to the Vienna score and the telangiectasia distribution pattern score (TDP); the impact of radiation proctitis on patients' lives was made according to the modified radiation toxicity score (MRTS) and hemoglobin levels. Number of sessions, duration of therapy, and adverse events were also compared between groups. The endoscopic therapeutic success (ETS) was defined by the absence or only few residual telangiectasias (TDP ≤1) on conclusion. RESULTS: An ETS of 92.8% was achieved in patients treated with APC and 92.3% for those treated with EFI (P > .05); there was an MRTS improvement of 85.7% in APC patients and 69.2% in EFI patients (P > .05). Mild adverse events occurred, respectively, in 23% and 28.5% in the EFI and APC groups (P > .05). CONCLUSIONS: The study showed that APC and EFI have similar efficacy and a high safety profile for HRP treatment. (Clinical trial registration number: 3.120.353.).

Antiedematogenic activity of the indole derivative N-salicyloyltryptamine in animal models.

The N-salicyloyltryptamine (NST) is an indole derivative compound analogue to the alkaloid N-benzoyltryptamine. In the present study, the antiedematogenic activity of NST was investigated in animal models. Firstly, the acute toxicity for NST was assessed according to the OECD Guideline no. 423. The potential NST-induced antiedematogenic activity was evaluated by carrageenan-induced paw edema in rats, as well as by dextran-, compound 48/80-, histamine-, serotonin-, capsaicine-, and prostaglandin E2-induced paw edema in mice. The effect of NST on compound 48/80-induced ex vivo mast cell degranulation on mice mesenteric bed was investigated. No death or alteration of behavioral parameters was observed after administration of NST (2000 mg/kg, i.p.) during the observation time of 14 days. The NST (100 and 200 mg/kg, i.p.) inhibited the carrageenan-induced edema from the 1st to the 5th hour (**p<0.01; ***p<0.001). The edematogenic activity induced by dextran, compound 48/80, histamine, serotonin, capsaicin, and prostaglandin E2 was inhibited by NST (100 mg/kg, i.p.) throughout the observation period (**p<0.01; ***p<0.001). The pretreatment with NST (50, 100 or 200 mg/kg, i.p) attenuates the compound 48/80-induced mast cell degranulation (**p<0.01; ***p<0.001). Thus, the inhibition of both mast cell degranulation and release of endogenous mediators are probably involved in the NST-induced antiedematogenic effect.

Antiedematogenic activity of the indole derivative N-salicyloyltryptamine in animal models

ABSTRACT The N-salicyloyltryptamine (NST) is an indole derivative compound analogue to the alkaloid N-benzoyltryptamine. In the present study, the antiedematogenic activity of NST was investigated in animal models. Firstly, the acute toxicity for NST was assessed according to the OECD Guideline no. 423. The potential NST-induced antiedematogenic activity was evaluated by carrageenan-induced paw edema in rats, as well as by dextran-, compound 48/80-, histamine-, serotonin-, capsaicine-, and prostaglandin E2-induced paw edema in mice. The effect of NST on compound 48/80-induced ex vivo mast cell degranulation on mice mesenteric bed was investigated. No death or alteration of behavioral parameters was observed after administration of NST (2000 mg/kg, i.p.) during the observation time of 14 days. The NST (100 and 200 mg/kg, i.p.) inhibited the carrageenan-induced edema from the 1st to the 5th hour (**p<0.01; ***p<0.001). The edematogenic activity induced by dextran, compound 48/80, histamine, serotonin, capsaicin, and prostaglandin E2 was inhibited by NST (100 mg/kg, i.p.) throughout the observation period (**p<0.01; ***p<0.001). The pretreatment with NST (50, 100 or 200 mg/kg, i.p) attenuates the compound 48/80-induced mast cell degranulation (**p<0.01; ***p<0.001). Thus, the inhibition of both mast cell degranulation and release of endogenous mediators are probably involved in the NST-induced antiedematogenic effect.

Gastroprotective effect of ethanol extracts of cladodes and roots of Pilosocereus gounellei (A. Weber ex K. Schum.) Bly. Ex Rowl (Cactaceae) on experimental ulcer models.

ETHNOPHARMACOLOGICAL RELEVANCE: Pilosocereus gounellei Cactaceae), popularly known as "xique xique", is a species native from Caatinga region of Northeast Brazil, which is used by traditional communities in folk medicine for a variety of health problems, especially inflammatory processes and gastritis. AIM OF THE STUDY: The present study investigates the possible gastric antiulceractivity of ethanol extracts obtained from the cladodes and roots of Pilosocereus gounellei (EECPG and EERPG, respectively) and mechanisms of action underlying this effect. MATERIALS AND METHODS: Mice were used for the evaluation of the acute toxicity, and mice and rats to study the gastroprotective activity. The gastroprotective action of EECPG and EERPG was analyzed in the absolute ethanol in mice, ischemia-reperfusion and cold restraint stress in rats. In the investigation of the gastroprotective mechanisms of EECPG and EERPG, the participation of the NO and prostaglandins, the levels of the non-protein sulfhydril groups (NP-SH) and the catalase activity using the ethanol-induced gastric mucosa lesion model and the quantification of the gastric mucus and the antisecretory activity through pylorus ligature model in rats were analyzed. RESULTS: The animals did not present any signs of acute toxicity for the EECPG and EERPG, and it was not possible to calculate the DL50. EECPG and EERPG (200 and 400 mg/kg) exhibited a significant gastroprotective effect in absolute ethanol, ischemia-reperfusion-induced and cold restraint stress gastric lesion models. Gastroprotection of EECPG and EERPG (200 mg/kg) was significantly decreased in pre-treated mice with L-NAME. Our studies revealed that EECPG and EERPG (200 mg/kg) prevented the decrease of the non-protein sulfhydril groups (NPSH) and increased the catalase levels in ethanol-treated animals. However, the gastric secretion parameters (volume, [H+], pH) did not show any alteration. CONCLUSIONS: Our results indicate that the ethanolic extract from the cladodes and roots of Pilosocereus gounellei exhibits a significant gastroprotection, because it inhibits the formation of gastric lesions using different models. The participation of the nitric oxide, prostaglandins, the non-protein sulfhydril groups (NP-SH), catalase seem to be involved in the gastroprotection activity of the EECPG and EERPG. Nevertheless, this activity does not seem to be related to antisecretory mechanisms.

Anti-inflammatory effect of the monoterpene myrtenol is dependent on the direct modulation of neutrophil migration and oxidative stress.

Myrtenol is a bicyclic monoterpene with anti-inflammatory properties. However, the mechanisms involved are partially unknown. Here, we investigated the effect of myrtenol during experimental chronic arthritis and the possible modulating activity of oxidative stress and neutrophil migration. Complete Freund's Adjuvant (CFA)-sensitized rats were treated with vehicle (1 mL/kg, po), myrtenol (12.5, 25 or 50 mg/kg, po), indomethacin (10 mg/kg, po) or dexamethasone (0.4 mg/kg) followed by intra-articular injection of CFA (0.5 mg/mL, 50 µL per joint). Then, paw edema and articular incapacitation (paw elevation time) were evaluated for 14 days. On the last day, a blood concentration superoxide dismutase (SOD) and nitrite was determined. In another experimental setting, human neutrophils were incubated with vehicle (sterile saline, 1 mL) or myrtenol (10-100 ng/mL) and the in vitro chemotaxis to N-formylmethionine-leucyl-phenylalanine (fMLP) (10-7 M/well) was evaluated. In addition, antiinflammatory effect of myrtenol was investigated in carrageenan-induced peritonitis. We found that CFA induced a prominent paw swelling and incapacitation of the joint, which were significantly prevented by myrtenol (P < 0.05). In addition, blood accumulation nitrite was attenuated by myrtenol when compared with vehicle-treated CFA group (P < 0.05). Furthermore, plasma levels of SOD were significantly increased by myrtenol versus vehicle-treated CFA group (P < 0.05). Moreover, fMLP-triggered neutrophil chemotaxis and carrageenan-induced peritonitis were markedly prevented by myrtenol (P < 0.05). Therefore, myrtenol showed anti-inflammatory and antinociceptive effects on experimental chronic arthritis, which seems to be related to the direct modulation of neutrophil migration and antioxidant activity.

α-Phellandrene, a cyclic monoterpene, attenuates inflammatory response through neutrophil migration inhibition and mast cell degranulation.

AIMS: We aimed to investigate the modulating effect of α-phellandrene on neutrophil migration and mast cell degranulation processes. MAIN METHODS: Male Wistar rats or Swiss mice were treated p.o. with vehicle (3% Tween 80, p.o.), α-phellandrene (50, 100, or 200mg/kg, p.o.), or dexamethasone (0.5mg/kg, p.o.) 1h before carrageenan injection. Then, the neutrophil migration in 6-day-old air pouches or peritoneal cavities. The leukocyte rolling and adhesion were measured in real time and assessed by intravital microscopy. ELISA was used to detect TNF-α and IL-6 in peritoneal lavage. Compound 48/80-induced mast cell degranulation was assessed in mesenteric rat tissues. KEY FINDINGS: In all the tested doses, α-phellandrene prevented carrageenan-induced neutrophil accumulation (P<0.05). As detected by intravital microscopy, α-phellandrene also inhibited leukocyte rolling and adhesion, as well as significantly inhibited the production of the pro-inflammatory cytokines TNF-α and IL-6. Moreover, the degranulation of compound 48/80-induced mast cells was also inhibited by α-phellandrene (P<0.001). SIGNIFICANCE: These results suggest that α-phellandrene plays an important role as an anti-inflammatory agent through neutrophil migration modulation and mast cell stabilization.

Anti-inflammatory and antinociceptive effects of Sterculia striata A. St.-Hil. & Naudin (Malvaceae) in rodents.

The present work reports the anti-inflammatory and antinociceptive activities of the ethanol extract obtained from the stem bark of Sterculia striata A. St.-Hil. & Naudin (Ss-EtOH) in the experimental models of edema induced by carrageenan, dextran, or histamin and nociception induced by chemical stimuli, such as acetic acid, formalin, capsaicin, or glutamate. The Ss-EtOH (50 mg/kg) promoted a marked inhibition on the hind paw edema induced by carrageenan or dextran (30% and 73%, respectively). Besides, Ss-EtOH (25 mg/kg) exhibited a slight activity (30%) on the hind paw edema induced by histamin. The Ss-EtOH (12.5 and 25 mg/kg) showed the antinociceptive activity on chemical stimuli induced by acetic acid (65.59% and 38.37%, respectively), formalin, in the initial (35.08% and 31.5%, respectively) and late phases (44.09% and 83.57%, respectively), capsaicin (43.77% and 51.31%, respectively), or glutamate (36.6% and 52.12%, respectively). Regarding the possible mechanism involved in the antinociceptive effect, Ss-EtOH (12.5 mg/kg) showed a decrease in the antinociceptive effect (65.8%) in the acetic acid model after pretreatment with naloxone. Thus, opioid mechanisms might be underlying this response.

Gastroprotective effect of an ethanolic extract from Neoglaziovia variegata (Arruda) Mez (Bromeliaceae) in rats and mice.

This study investigates the gastroprotective effect of a crude ethanolic extract of Neoglaziovia variegata (Arruda) Mez (Bromeliaceae), designated Nv-EtOH, in experimental models of gastric ulcer. In the ethanol-induced gastric ulcer model, Nv-EtOH showed gastroprotection at doses of 200 and 400 mg/kg body weight (BW) (57.0% and 79.7%, respectively). Nv-EtOH also significantly reduced the formation of gastric lesions induced by ethanol/HCl (31.6% and 63.5%), ibuprofen (70.0% and 74.3%), or ischemia/reperfusion in rats (65.0% and 87.0%) at 200 and 400 mg/kg BW when compared with the vehicle group. In the antioxidant activity assessment, Nv-EtOH (400 mg/kg BW) increased the catalase activity and sulfhydryl groups (SH) levels, respectively. Moreover, gastroprotection against ethanol damage was decreased after ibuprofen pretreatment. Nv-EtOH (400 mg/kg BW) promoted a significant increase in the content of gastric wall mucus. The Nv-EtOH effect was significantly reduced in mice pretreated with N(G)-nitro-L-arginine (L-NOARG) or glibenclamide, inhibitors of nitric oxide synthase and K(ATP) channel activation, respectively, suggesting the involvement of these mechanisms in the Nv-EtOH-induced gastroprotective effect. Nv-EtOH decreased the total acidity, but did not modify other gastric juice parameters. Nv-EtOH was also effective in promoting the healing process in chronic gastric ulcer induced by acetic acid in rats.

Anti-inflammatory and anti-ulcer activities of carvacrol, a monoterpene present in the essential oil of oregano.

This study reports a pharmacological evaluation of anti-inflammatory and anti-ulcer activities of carvacrol, a phenolic monoterpene constituent of essential oils produced by oregano and other several aromatic plants and spices, in experimental models of edema induced by different phlogistic agents and gastric lesions induced by acetic acid. In models of paw edema induced by dextran or histamine, carvacrol was effective at 50 mg/kg (46% and 35%, respectively); in these models, cyproheptadine reduced edema formation (61% and 43%, respectively). In edema induced by substance P, carvacrol (100 mg/kg) and ruthenium red (3 mg/kg) also decreased the edema formation (46% and 40%, respectively). Carvacrol significantly reduced the ear edema induced by 12-O-tetradecanoylphorbol acetate and arachidonic acid at 0.1 mg per ear (43% and 33%, respectively), similar to indomethacin at 0.5 mg per ear or 2.0 mg per ear (55% and 57%, respectively). Carvacrol (at doses of 25, 50, and 100 mg/kg) showed a healing capacity on gastric lesions induced by acid acetic (60%, 91%, and 81%, respectively) after 14 days of treatment. These results suggest that carvacrol acts on different pharmacological targets, probably interfering in release and/or synthesis of inflammatory mediators, such as the prostanoids, and thus favoring the healing process for gastric ulcers.

Gastroprotective activity of Sterculia striata A. St. Hil. & Naudin (Malvaceae) in rodents.

The Sterculia striata ethanolic extract (Ss-EtOH) inhibited gastric lesions induced by ethanol, HCl/ethanol, and ischemia/reperfusion, but not those induced by indomethacin, and did not alter the gastric secretion. Ss-EtOH restored the catalase activity and content of nonprotein sulfhydryl groups in the stomach of mice treated with ethanol. The gastroprotection induced by Ss-EtOH in the ethanol-induced gastric lesion model was abolished by N(G)-nitroL-arginine methyl ester (L-NAME) pretreatment, suggesting the involvement of nitric oxide and antioxidant compounds, but not prostaglandins, in this activity. Lupeol obtained from Ss-EtOH promoted gastroprotection as well as the extract at the same dose, and it must therefore contribute to the observed effects.

Antiulcer activity of ethanolic extract of Encholirium spectabile Mart. ex Schult & Schult f. (Bromeliaceae) in rodents.

This study evaluated the antiulcer activity of an ethanolic extract of Encholirium spectabile (ES-EtOH) by using different standard experimental models of induced acute gastric ulceration. ES-EtOH (100 mg/kg p.o) protected the gastric mucosa against ulceration that was induced by absolute ethanol (53%), ethanol/HCl (75%), ibuprofen (52 %) and ischemia/reperfusion (43 %). It also restored catalase activity and non-protein sulfhydryl group concentration in the gastric wall of mice that had been treated with ethanol. The pre-treatment of mice with N-nitro-L-arginine (70 mg/kg i.p.) abolished the protective activity of ES-EtOH, which indicates that prostaglandins, antioxidant compounds and nitric oxide synthase activity are involved in the gastroprotective activity of the extract.

Gastroprotective effect of the ethanolic extract of Parkia platycephala Benth. leaves against acute gastric lesion models in rodents.

Parkia platycephala Benth. (Leguminosae--Mimosoideae), popularly known as "visgueira", fava bean tree or "fava-de-bolota", is widely found in the Northern and Northeastern regions of Brazil. Its pods are used as cattle food supplement in the drought period. Compounds with a gastroprotective activity were obtained from the genus Parkia. Therefore, this study aimed at investigating the gastroprotective effect of the ethanolic extract of Parkia platycephala Benth. leaves (Pp-EtOH), as well as evaluating its possible mechanisms of action in experimental ulcer induction models. Lesions were induced by absolute ethanol, ethanol-HCl, ischemia-reperfusion and indomethacin in rodents. Pp-EtOH showed a protective effect in the lesion models (66, 48 and 52%, respectively), but it was not able to protect gastric mucosa against indomethacin-induced lesions. Results show a possible participation of the NO-synthase pathway in the gastroprotection and an antioxidant activity, by the increase of the catalase activity. The participation of prostaglandins and potassium channels sensitive to ATP in the gastroprotective effect of Pp-EtOH seems less likely to occur. More comprehensive studies, therefore, should be carried out to elucidate the antiulcerative effects of this promising natural product against this gastrointestinal disorder.

Gastroprotective effect of the ethanolic extract of Parkia platycephala Benth. leaves against acute gastric lesion models in rodents

Parkia platycephala Benth. (Leguminosae - Mimosoideae), popularly known as "visgueira", fava bean tree or "fava-de-bolota", is widely found in the Northern and Northeastern regions of Brazil. Its pods are used as cattle food supplement in the drought period. Compounds with a gastroprotective activity were obtained from the genus Parkia. Therefore, this study aimed at investigating the gastroprotective effect of the ethanolic extract of Parkia platycephala Benth. leaves (Pp-EtOH), as well as evaluating its possible mechanisms of action in experimental ulcer induction models. Lesions were induced by absolute ethanol, ethanol-HCl, ischemia-reperfusion and indomethacin in rodents. Pp-EtOH showed a protective effect in the lesion models (66, 48 and 52 percent, respectively), but it was not able to protect gastric mucosa against indomethacin-induced lesions. Results show a possible participation of the NO-synthase pathway in the gastroprotection and an antioxidant activity, by the increase of the catalase activity. The participation of prostaglandins and potassium channels sensitive to ATP in the gastroprotective effect of Pp-EtOH seems less likely to occur. More comprehensive studies, therefore, should be carried out to elucidate the antiulcerative effects of this promising natural product against this gastrointestinal disorder.

Antiulcer activity of ethanolic extract of Encholirium spectabile Mart. ex Schult & Schult f. (Bromeliaceae) in rodents

This study evaluated the antiulcer activity of an ethanolic extract of Encholirium spectabile (ES-EtOH) by using different standard experimental models of induced acute gastric ulceration. ES-EtOH (100 mg/kg p.o) protected the gastric mucosa against ulceration that was induced by absolute ethanol (53 percent), ethanol/HCl (75 percent), ibuprofen (52 percent) and ischemia/reperfusion (43 percent). It also restored catalase activity and non-protein sulfhydryl group concentration in the gastric wall of mice that had been treated with ethanol. The pre-treatment of mice with N-nitro-L-arginine (70 mg/kg i.p.) abolished the protective activity of ES-EtOH, which indicates that prostaglandins, antioxidant compounds and nitric oxide synthase activity are involved in the gastroprotective activity of the extract.

Hypotensive and endothelium-independent vasorelaxant effects of methanolic extract from Curcuma longa L. in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Curcuma longa L. (CL) is a yellow rhizome that is used in African traditional medicine to treat palpitation, hypertension or other related blood circulation disorders. AIM OF THE STUDY: To justify the use of CL in ethnomedicine, we investigated the vasorelaxant effect of methanolic extract of CL (CLME) and its underlying mechanisms in isolated rat mesenteric artery. MATERIALS AND METHODS: The effect of CLME on the mean arterial pressure (MAP) and heart rate (HR) (pulse interval) were determined in vivo in non-anaesthetized rats. Superior mesenteric rings were isolated, suspended in organ baths containing Tyrode solution at 37 degrees C and gassed with 95% O(2)+5% CO(2), under a resting tension of 0.75 g. The vasorelaxant effects of CLME were studied by means of isometric tension recording experiments. RESULTS: In normotensive rats, CLME (10, 20 and 30 mg/kg, i.v.) induced dose-dependent hypotension (2.0+/-0.5%; 27.1+/-5.0% and 26.7+/-4.6%, respectively), and pronounced bradycardia (5.8+/-1.2%, 19.3+/-3.2% and 22.9+/-4.6%, respectively). CLME (1-1000 microg/mL) induced concentration-dependent relaxation of tonic contractions evoked by phenylephrine (Phe) (10 microM) and KCl (80 mM) in rings with intact-endothelium (E(max)=82.3+/-3.2% and 97.7+/-0.7%) or denuded-endothelium (E(max)=91.4+/-1.0% and 97.8+/-1.1%). Also, in a depolarized, Ca(2+) free medium, CLME inhibited CaCl(2) (1 microM-30 mM)-induced contractions and caused a concentration-dependent rightward shift of the response curves, indicating that CLME inhibited the contractile mechanisms involving extracellular Ca(2+) influx. In addition, in Ca(2+) free media containing EGTA (1 mM), CLME inhibited the transient contraction of denuded rings constricted with Phe, but not those evoked by caffeine (20 mM). In contrast, neither glibenclamide, BaCl(2), tetraethylammonium nor 4-aminopyridine affected CLME-induced relaxation. CONCLUSIONS: These results demonstrate the hypotensive and bradycardic effects of CLME, as well as its potent vasodilation of rat mesenteric arteries. These effects, may in part, be due to the inhibition of extracellular Ca(2+) influx and/or inhibition of intracellular Ca(2+) mobilization from Phe-sensitive stores.

Attenuation of visceral nociception by alpha- and beta-amyrin, a triterpenoid mixture isolated from the resin of Protium heptaphyllum, in mice.

In the search for novel natural compounds effective against visceral nociception, the triterpenoid mixture alpha- and beta-amyrin, isolated from Protium heptaphyllum resin, was assessed in two established mouse models of visceral nociception. Mice were pretreated orally with alpha- and beta-amyrin (3, 10, 30, and 100 mg/kg) or vehicle, and the pain-related behavioral responses to intraperitoneal cyclophosphamide or to intracolonic mustard oil were analyzed. The triterpenoid mixture showed a dose-related significant antinociception against the cyclophosphamide-induced bladder pain, and at 100 mg/kg, the nociceptive behavioral expression was almost completely suppressed. Intracolonic mustard oil-induced nociceptive behaviors were maximally inhibited by 10 mg/kg alpha- and beta-amyrin mixture in a naloxone-reversible manner. While pretreatment with ruthenium red (3 mg/kg, s. c.), a non-specific transient receptor potential cation channel V1 (TRPV1) antagonist, also caused significant inhibition, the alpha (2)-adrenoceptor antagonist, yohimbine (2 mg/kg, s. c.), showed no significant effect. The triterpene mixture (10 mg/kg, p. o.) neither altered significantly the pentobarbital sleeping time, nor impaired the ambulation or motor coordination in open-field and rotarod tests, respectively, indicating the absence of sedative or motor abnormalities that could account for its antinociception. These results indicate that the antinociceptive potential of alpha- and beta-amyrin possibly involves the opioid and vanilloid (TRPV1) receptor mechanisms and further suggests that it could be useful to treat visceral pain of intestinal and pelvic origins.

Cardiovascular effects of trans-dehydrocrotonin, a diterpene from Croton cajucara in rats.

Previous studies have established the gastroprotective, hypoglycemic, and hypolipidemic effects of trans-dehydrocrotonin (t-DCTN), a major diterpene isolated from the Amazon medicinal plant Croton cajucara. This study aims to examine the potential effects of t-DCTN on hemodynamic parameters that include resting arterial blood pressure and heart rate in vivo, and on left atrial force, spontaneous beating atria, and aortic rings of rats in vitro. Intravenous bolus injections of t-DCTN (5, 10, or 15 mg/kg) to urethane anesthetized normotensive rats reduced the mean arterial pressure and heart rate in a dose-dependent manner. The hypotensive effect of t-DCTN (10 mg/kg) appears not mediated through effects on the muscarinic cholinergic receptor, beta-adrenoceptor, or ganglionic blockade, for it was not affected by atropine, propranolol, or hexamethonium but was abolished by N(w)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor. The diterpene t-DCTN showed no significant influence on inotropism. In isolated rat aortic rings with intact or denuded endothelium, t-DCTN relaxed the tonic contraction induced by phenylephrine (1 microM). Its vasorelaxant effect seen at smaller concentrations in endothelium intact preparations was, however, abolished in endothelium denuded or in l-NAME treated tissues. These data indicate the hypotensive and bradycardia effects of t-DCTN, possibly related in part to the release of nitric oxide and in part to direct effects on vascular smooth muscle, and cardiac pacemaker activity.

Attenuation of capsaicin-induced acute and visceral nociceptive pain by alpha- and beta-amyrin, a triterpene mixture isolated from Protium heptaphyllum resin in mice.

The triterpene mixture, alpha- and beta-amyrin, isolated from Protium heptaphyllum resin was evaluated on capsaicin-evoked nociception in mice. Orally administered alpha- and beta-amyrin (3 to 100 mg/kg) significantly suppressed the nociceptive behaviors--evoked by either subplantar (1.6 microg) or intracolonic (149 microg) application of capsaicin. The antinociception produced by alpha- and beta-amyrin against subplantar capsaicin-induced paw-licking behavior was neither potentiated nor attenuated by ruthenium red (1.5 mg/kg, s.c.), a non-specific antagonist of vanilloid receptor (TRPV1), but was greatly abolished in animals pretreated with naloxone (2 mg/kg, s.c.), suggesting an opioid mechanism. However, participation of alpha2-adrenoceptor involvement was unlikely since yohimbine (2 mg/kg, i.p.) pretreatment failed to block the antinociceptive effect of alpha- and beta-amyrin in the experimental model of visceral nociception evoked by intracolonic capsaicin. The triterpene mixture (3 to 30 mg/kg, p.o.) neither altered significantly the pentobarbital sleeping time, nor impaired the ambulation or motor coordination in open-field and rota-rod tests, respectively, indicating the absence of sedative or motor abnormality that could account for its antinociception. Nevertheless, alpha- and beta-amyrin could significantly block the capsaicin (10 mg/kg, s.c.)-induced hyperthermic response but not the initial hypothermia. These results suggest that the triterpene mixture, alpha- and beta-amyrin has an analgesia inducing effect, possibly involving vanilloid receptor (TRPV1) and an opioid mechanism.

Protective effect of alpha- and beta-amyrin, a triterpene mixture from Protium heptaphyllum (Aubl.) March. trunk wood resin, against acetaminophen-induced liver injury in mice.

In the search of hepatoprotective agents from natural sources, alpha- and beta-amyrin, a triterpene mixture isolated from the trunk wood resin of folk medicinal plant, Protium heptaphyllum was tested against acetaminophen-induced liver injury in mice. Liver injury was analysed by quantifying the serum enzyme activities and by histopathological observations. In mice, acetaminophen (500 mg/kg, p.o.) caused fulminant liver damage characterized by centrilobular necrosis with inflammatory cell infiltration, an increase in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, a decrease in hepatic glutathione (GSH) and 50% mortality. Pretreatment with alpha- and beta-amyrin (50 and 100 mg/kg, i.p. at 48, 24, and 2 h before acetaminophen) attenuated the acetaminophen-induced acute increase in serum ALT and AST activities, replenished the depleted hepatic GSH, and considerably reduced the histopathological alterations in a manner similar to N-acetylcysteine, a sulfhydryls donor. Also, the acetaminophen-associated mortality was completely suppressed by terpenoid pretreatment. Further, alpha- and beta-amyrin could potentiate the pentobarbital (50 mg/kg, i.p.) sleeping time, suggesting the possible suppression of liver cytochrome-P450. These findings indicate the hepatoprotective potential of alpha- and beta-amyrin against toxic liver injury and suggest that the diminution in oxidative stress and toxic metabolite formation as likely mechanisms involved in its hepatoprotection. In conclusion, this study supports the traditional use of Protium heptaphyllum resin as a medicinal agent and suggests the feasibility of developing herbal drugs for treatment of liver disorders.