滇重楼甾体皂苷对大鼠乙醇或吲哚美辛诱导的胃黏膜损伤的保护作用：活性的结构要求及作用方式
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.
作者信息
Matsuda Hisashi, Pongpiriyadacha Yutana, Morikawa Toshio, Kishi Akinobu, Kataoka Shinya, Yoshikawa Masayuki
机构信息
Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan.
出版信息
Bioorg Med Chem Lett. 2003 Mar 24;13(6):1101-6. doi: 10.1016/s0960-894x(03)00052-0.
The methanolic extract from the rhizomes of Paris polyphylla SM. var. yunnanensis (FR.) 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-alpha-L-rhamnopyranosyl(1-->2)-[alpha-L-arabinofuranosyl(1-->4)]-beta-D-glucopyranoside (1), pennogenin 3-O-alpha-L-rhamnopyranosyl(1-->4)-alpha-L-rhamnopyranosyl(1-->4)-[alpha-L-rhamnopyranosyl(1-->2)]-beta-D-glucopyranoside (2), diosgenin 3-O-alpha-L-rhamnopyranosyl(1-->2)-[alpha-L-arabinofuranosyl(1-->4)]-beta-D-glucopyranoside (3), and diosgenin 3-O-alpha-L-rhamnopyranosyl(1-->4)-alpha-L-rhamnopyranosyl(1-->4)-[alpha-L-rhamnopyranosyl(1-->2)]-beta-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.
七叶一枝花云南重楼根茎的甲醇提取物被发现能有效抑制大鼠乙醇诱导的胃损伤。通过生物活性导向分离，从活性部位分离出4种已知的螺甾烷型甾体皂苷，即偏诺皂苷元3 - O -α - L - 鼠李吡喃糖基(1→2)-[α - L - 阿拉伯呋喃糖基(1→4)]-β - D - 葡萄糖吡喃糖苷(1)、偏诺皂苷元3 - O -α - L - 鼠李吡喃糖基(1→4)-α - L - 鼠李吡喃糖基(1→4)-[α - L - 鼠李吡喃糖基(1→2)]-β - D - 葡萄糖吡喃糖苷(2)、薯蓣皂苷元3 - O -α - L - 鼠李吡喃糖基(1→2)-[α - L - 阿拉伯呋喃糖基(1→4)]-β - D - 葡萄糖吡喃糖苷(3)、薯蓣皂苷元3 - O -α - L - 鼠李吡喃糖基(1→4)-α - L - 鼠李吡喃糖基(1→4)-[α - L - 鼠李吡喃糖基(1→2)]-β - D - 葡萄糖吡喃糖苷(4)，以及1种新的呋甾烷型甾体皂苷，重楼皂苷I(5)，还有2种已知的呋甾烷型甾体皂苷，三角叶皂苷A(6)和原纤细皂苷(7)。化合物1 - 4(1.25 - 10 mg/kg，口服)能强烈抑制乙醇和吲哚美辛诱导的胃损伤。关于甾体皂苷的结构要求，发现3 - O - 糖苷部分和螺甾烷结构对活性至关重要，苷元部分的17 - 羟基增强了对乙醇诱导胃损伤的保护作用。吲哚美辛和N - 乙基马来酰胺预处理可减弱1和3对乙醇诱导胃损伤的保护作用。化合物1和3对幽门结扎大鼠的胃酸分泌有微弱抑制作用。这些结果表明内源性前列腺素和巯基化合物参与了保护活性。
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