Yamauchi K, Shinano K, Nakajima K, Yagi T, Kuwano S
Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Hyogo, Japan.
J Pharm Pharmacol. 1992 Dec;44(12):973-6. doi: 10.1111/j.2042-7158.1992.tb07076.x.
Sennosides A and C directly injected into the caecum of mice showed equal purgative activity. Intracaecal administration reduced time to onset of diarrhoea induced by sennoside C from about 3 h after oral administration to about 24 min. At 2.3 h after oral administration of sennoside C, nearly equimolar amounts of aloe-emodin anthrone and rhein anthrone were detected in the large intestine of mice. The purgative effect of oral sennoside C could be reduced by pretreating mice with chloramphenicol. This was observed as a decreased formation of total anthrones in the large intestine. Both anthrones and an equimolar mixture of both anthrones directly injected into the caecum exerted a purgative effect, although the activity was lower for aloe-emodin anthrone. The intracaecal ED50 values were 54.5 (24.1-89.6), 11.4 (5.0-15.7) and 11.2 (6.1-14.6) mumol kg-1 for aloe-emodin anthrone, rhein anthrone and an equimolar mixture of both anthrones, respectively. We concluded that aloe-emodin anthrone and rhein anthrone, formed mainly by intraluminal bacterial action, are the true active metabolites of sennoside C in mice and that both anthrones synergistically exert their purgative effects on mice.
直接注射到小鼠盲肠中的番泻苷A和C显示出相同的泻下活性。盲肠内给药将番泻苷C诱导腹泻的起效时间从口服给药后约3小时缩短至约24分钟。口服番泻苷C后2.3小时，在小鼠大肠中检测到几乎等摩尔量的芦荟大黄素蒽酮和大黄酸蒽酮。用氯霉素预处理小鼠可降低口服番泻苷C的泻下作用。这表现为大肠中总蒽酮的形成减少。直接注射到盲肠中的蒽酮及其等摩尔混合物均具有泻下作用，尽管芦荟大黄素蒽酮的活性较低。芦荟大黄素蒽酮、大黄酸蒽酮及其等摩尔混合物的盲肠内ED50值分别为54.5（24.1 - 89.6）、11.4（5.0 - 15.7）和11.2（6.1 - 14.6）μmol kg-1。我们得出结论，主要由肠腔内细菌作用形成的芦荟大黄素蒽酮和大黄酸蒽酮是小鼠体内番泻苷C真正的活性代谢产物，且两种蒽酮对小鼠具有协同泻下作用。
