Chrysophanol, a major anthraquinone component occurring in many traditional 
Chinese herbs, is accepted as important active component with various 
pharmacological actions such as antibacterial and anticancer activity. Previous 
studies demonstrated that exposure to chrysophanol induced cytotoxicity, but the 
mechanisms of the toxic effects remain unknown. In the present metabolism study, 
three oxidative metabolites (M1-M3, aloe-emodine, 7-hydroxychrysophanol, and 
2-hydroxychrysophanol) and five GSH conjugates (M4-M8) were detected in rat and 
human liver microsomal incubations of chrysophanol supplemented with GSH, and 
the formation of the metabolites was NADPH dependent except M4 and M5. M4 and M5 
were directly derived from parent compound chrysophanol, M6 arose from M2, and 
M7 and M8 resulted from the oxidation of M4 and M5. Metabolites M5 and M6 were 
also observed in bile of rats after exposure to chrysophanol, M1-M3 and one NAC 
conjugate (M9) were detected in urine of rats administrated chrysophanol, and 
urinary metabolite M9 originated from the degradation of biliary GSH conjugation 
M6. Recombinant P450 enzyme incubation and microsome inhibition studies 
demonstrated that P450 1A2 was the primary enzyme responsible for the metabolic 
activation of chrysophanol and that P450 2B6 and P450 3A4 also participated in 
the generation of the oxidative metabolites. These findings helped us to 
understand the mechanisms of chrysophanol-induced cytotoxicity.