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

The methanolic extract from the rhizomes of Paris polyphylla S . var. yunnanensis (F .) 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- -rhamnopyranosyl(1→2)-[α- -arabinofuranosyl(1→4)]-β- -glucopyranoside (1), pennogenin 3-O-α- -rhamnopyranosyl(1→4)-α- -rhamnopyranosyl(1→4)-[α- -rhamnopyranosyl(1→2)]-β- -glucopyranoside (2), diosgenin 3-O-α- -rhamnopyranosyl(1→2)-[α- -arabinofuranosyl(1→4)]-β- -glucopyranoside (3), and diosgenin 3-O-α- -rhamnopyranosyl(1→4)-α- -rhamnopyranosyl(1→4)-[α- -rhamnopyranosyl(1→2)]-β- -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.