Gastroprotective effect of lupeol on ethanol-induced gastric damage and the underlying mechanism.

The effect of lupeol, a natural pentacyclic triterpene on ethanol-induced gastric damage in mice was evaluated. The gastroprotection was assessed by determination of changes in mean gastric lesion area, quantification of mucosal non-protein sulfhydryls (NP-SH), and characterized using drugs that influence the endogenous prostaglandins, alpha(2)-adrenoceptors, nitric oxide, K(ATP)-channels, and intracellular calcium. Orally administered lupeol (3, 10, and 30 mg/kg) significantly and dose-dependently attenuated the ethanol-induced gastric damage by 39-69%, whereas the positive control N-acetylcysteine (NAC, 300 mg/kg, i.p.) afforded 32% protection. Both lupeol and NAC restored the NP-SH depleted by ethanol but the lupeol effect was only marginal. Lupeol gastroprotection was attenuated by indomethacin and L-NAME, the respective COX and NO-synthase inhibitors and was weakly sensitive to alpha(2)-adrenergic antagonist yohimbine and K(ATP)-channel blocker glibenclamide, but more profoundly to calcium blocker verapamil. These pharmacological effects of lupeol may synergistically contribute to alleviating the ethanol-associated gastric damage, which is multifactorial.

Gastroprotective effect of mangiferin, a xanthonoid from Mangifera indica, against gastric injury induced by ethanol and indomethacin in rodents.

In search of novel gastroprotective agents, mangiferin, a naturally occurring glucosylxanthone from Mangifera indica L. (Anacardiaceae), was evaluated in mice on gastric injury induced by ethanol and indomethacin. The effects of mangiferin on gastric mucosal damage were assessed by determination of changes in mean gastric lesion area or ulcer score in mice and on gastric secretory volume and total acidity in 4-h pylorus-ligated rats. Mangiferin (3, 10 and 30 mg/kg, P. O.) significantly attenuated the gastric damage induced by ethanol by 30, 35, and 63 %, and of indomethacin by 22, 23 and 57 %, respectively. N-Acetylcysteine (750 mg/kg, I. P.) and lansoprazole (30 mg/kg, P. O.) used as positive controls in these ulcerogenic models resulted in 50 % and 76 % suppression of gastric injury, respectively. In 4-h pylorus-ligated rats, intraduodenally applied mangiferin (30 mg/kg) caused significant diminutions in gastric secretory volume and total acidity. In addition, like N-acetylcysteine, a donor of sulfhydryls, mangiferin effectively prevented the ethanol-associated depletion of gastric mucosal non-protein sulfhydryl content in mice, suggesting an antioxidant action. These findings provide evidence that mangiferin affords gastroprotection against gastric injury induced by ethanol and indomethacin most possibly through the antisecretory and antioxidant mechanisms of action.

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.