天然物對腸胃道之作用 第一報：類三帖類對天竺鼠胃及十二指腸穿透作用之探討

Natural Products on Gastrointestinal System I.Effects of Triterpenoids on the Permeability of Stomach and Duodenum Guinea Pigs

劉惠娥(Hui-Erh Liu)

指導教授 ： 廖嘉鴻 ； 顏焜熒 ； 楊玲玲

臺北醫學大學/藥學院/生藥學研究所/碩士(1995年)

摘要

三帖羧酸 (triterpene carboxylic acids):自樺酸 (betulinic acid; BA)、齊墩果酸(oleanolic acid;OA)、熊果酸(ursolic acid;UA)及類三帖皂素（如甘草皂素，glycyrrhizic acid，GZA）富含於某些中藥，由於這些三帖羧酸與膽固醇之化學結構類似，因此本研究擬探討BA、OA、UA及GZA等化合物是否具保護或安定細飽膜之作用。 組織電阻(tissue resistance)及細胞膜之穿透性為細跑膜安定性之參考指標。本研究利用Diffusion cells之裝置進行藥物對天竺鼠胃、十二指腸之體外穿透試驗，發現UA及OA(約0.5mM)均可顯著抑制(>40%)14C-eitradini在胃、腸之穿透作用，而BA及GZA(0.375mM)則僅分別在 胃及腸有類似作用。對14C-mannitol之穿透，在胃中則僅UA可增加約39%，GZA降低約29%。在十二指腸中，則僅OA可降低約25%，BA增加約44%。這些對胃、腸穿透作用之抑制或增加，大致相對她與測試之tissue resistance之提高或下降相符合。 利用radioimmunoassay方法對胃細飽內cAMP之含量影響試驗中，發現RA可明輟增加cAMP之含量(34%)，而GZA則降低 (21%);但四個藥物對十二指腸細砲內cAMP之含量均無明顯影響。相對於本研究之phospnodiesterase作用速率之試驗發現除BA略降(8%)外，其於三者均略增 (∼10%)此酵素之作用速率。此結果與對胃細胞內cAMP之含量影響較符合。 本研究藉由對胃、十二指腸之穿透與電阻試驗發現三帖羧酸BA、OA、UA及GZA大致可安定細胞膜，而抑制脂溶性成分(經transcellular pathway)在胃、十二指腸細砲膜之穿透吸收，這些作用可能歸因於與膽固醇之結構類似，而與cAMP及phosphodiesterase之作用較無關係。

關鍵字

天然物 ； 十二指腸

並列摘要

Some triterpene carboxylic acids- betulinic acid (BA), oleanolic acid (OA), and ursolic acid (UA), and triterpenoid saponins, e.g. glycyrrhizic acid (GZA) are rich in traditional Chinese medicines. Their chemical structures are similar to that of cholesterol, a component for the stabilization of cell membrane. Based on these, this study was aimed to investigate whether these compounds could protect or stabilize the cell membranes. Tissue resistance and membrane permeability, both measured in the apparatus of diffusion cells, are two indexes for membrane stability'. This study revealed that UA and OA (about 0.5mM) inhibited the penetration of 14C-labeled estradiol at least 40% through stomach and duodenum. However, BA and GZA possessed similar activity only to stomach and duodenum, respectively. As for the effect on 14C-labeled mannitol penetration, UA enhanced 39% while GZA inhibited 29% in the stomach, and OA inhibited 25% while BA enhanced 44% in the duodenum. Their effect on the tissue resistance was generally consistent with the outcome of penetration study. The relationship between the effect of membrane transport and the amount of cAMP in cells in the presence of tested compounds was also studied. The amount of cAMP measured by radioimmunoassay was found to increase 34% by BA but decrease 21% by GZA in stomach cells. However, there were no apparently different in duodenal cells in the presence of the tested compounds. The result in the stomach cells is roughly consistent with their effect on the reaction rate of phosphodiesterase which showed a little decrease (8%) by BA and a little increase (10 to 16%) by the other three compounds. By means of measuring tissue penetration and resistance, we found that triterpene carboxylic acids BA, OA, UA and GZA could stabilize cell membrane resulting the inhibition against penetration for lipophilic compounds (transport via transcellular pathway) through stomach and duodenal cell membranes. This effect would be ascribed to their structural similarity to cholesterol rather than their effect of the content of cAMP in the cells.