Protective effects of steroid saponins from paris polyphylla var. yunnanensis on ethanol- or indomethacin-induced gastric mucosal lesions in rats: structural requirement for activity and mode of action

Abstract

The methanolic extract from the rhizomes of Paris polyphylla S m. var . yunnanensis (F r.) H-M. was found to potently inhibit ethanol-induced gastric lesions in rats. Through bioassay-guided separation, four known spirostanol-type steroid saponins, pennogenin 3- O-α- l-rhamnopyranosyl(1→2)-[α- l-arabinofuranosyl(1→4)]-β- d-glucopyranoside ( 1), pennogenin 3- O-α- l-rhamnopyranosyl(1→4)-α- l-rhamnopyranosyl(1→4)-[α- l-rhamnopyranosyl(1→2)]-β- d-glucopyranoside ( 2), diosgenin 3- O-α- l-rhamnopyranosyl(1→2)-[α- l-arabinofuranosyl(1→4)]-β- d-glucopyranoside ( 3), and diosgenin 3- O-α- l-rhamnopyranosyl(1→4)-α- l-rhamnopyranosyl(1→4)-[α- l-rhamnopyranosyl(1→2)]-β- d-glucopyranoside ( 4), and a new furostanol-type steroid saponin, parisaponin I ( 5), together with two known furostanol-type steroid saponins, trigofoenoside A ( 6) and protogracillin ( 7), were isolated from the active fraction. Compounds 1– 4 (1.25–10 mg/kg, po) strongly inhibited gastric lesions induced by ethanol and indomethacin. With regard to structural requirement of steroid saponins, the 3- O-glycoside moiety and spirostanol structure were found to be essential for the activity and the 17-hydroxyl group in the aglycon part enhanced the protective effects against ethanol-induced gastric lesions. The protective effects of 1 and 3 against ethanol-induced gastric lesions were attenuated by pretreatment with indomethacin and N-ethylmaleimide. Compounds 1 and 3 weakly inhibited acid secretions in pylorus-ligated rats. These findings suggested that endogenous prostaglandins and sulfhydryl compounds were involved in the protective activity.