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.
Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Hyogo, Japan.
K
K
Yamauchi
K
K
Shinano
K
K
Nakajima
T
T
Yagi
S
S
Kuwano
D000818:Animals; D000873:Anthracenes / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D000880:Anthraquinones / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D003967:Diarrhea / Q000139:chemically induced; D004357:Drug Synergism; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D012676:Senna Extract
D000873:Anthracenes; D000880:Anthraquinones; D012676:Senna Extract; C029839:sennoside C