Metabolic activation of sennoside C in mice: synergistic action of anthrones

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.