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.

邻苯二酚是许多传统中草药中存在的主要蒽醌成分，被认为是具有多种药理作用（如抗菌和抗癌活性）的重要活性成分。先前的研究表明，暴露于草ry酚会诱导细胞毒性，但其毒性作用的机制仍不清楚。在当前的代谢研究中，在大鼠和人肝脏中补充了谷胱甘肽的谷胱甘肽温育中，检测到三种氧化代谢物（M1-M3，芦荟-大黄素，7-羟基菜豆酚和2-羟基菜豆酚）和五种谷胱甘肽结合物（M4-M8）。 ，而代谢产物的形成是NADPH依赖性的，除了M4和M5。M4和M5直接衍生自母体化合物chsophophanol，M6来自M2，M7和M8源自M4和M5的氧化。暴露于中性酚的大鼠胆汁中也观察到代谢产物M5和M6，在经中性酚的大鼠尿液中检测到M1-M3和一种NAC共轭物（M9），尿代谢产物M9源自胆汁GSH结合M6的降解。重组P450酶的温育和微粒体抑制研究表明，P450 1A2是负责酚的代谢活化的主要酶，P450 2B6和P450 3A4也参与了氧化代谢产物的产生。这些发现帮助我们了解了中毒酚诱导的细胞毒性的机制。尿中的代谢物M9源自胆汁GSH共轭物M6的降解。重组P450酶的温育和微粒体抑制研究表明，P450 1A2是负责酚的代谢活化的主要酶，P450 2B6和P450 3A4也参与了氧化代谢产物的产生。这些发现帮助我们了解了中毒酚诱导的细胞毒性的机制。尿代谢产物M9源自胆道谷胱甘肽结合蛋白M6的降解。重组P450酶的温育和微粒体抑制研究表明，P450 1A2是负责酚的代谢活化的主要酶，P450 2B6和P450 3A4也参与了氧化代谢产物的产生。这些发现帮助我们了解了中毒酚诱导的细胞毒性的机制。