Chemical Reactivity of Aloe-Emodin and Its Hydroxylation Metabolites to Thiols

Aloe-emodin (AE), an anthraquinone derivative, is a bioactive ingredient isolated from rhubarb which is used to treat inflammatory illnesses in China and many other countries in Asia. AE has shown a wide range of pharmacological effects. Recent studies showed that exposure to AE could cause DNA damage and cytotoxicity. The goals of the present study are aimed at (1) exploration of oxidative metabolism pathways of AE, (2) identification of P450 enzymes which respond the hydroxylation of AE, and (3) determination of electrophilicity of AE and its oxidative metabolites. Two hydroxylation metabolites (M1 and M2) and four GSH conjugates (M3-M6) were found in incubations consisting of AE, rat or human liver microsomes, and NADPH supplemented with GSH. Conjugates M3 and M4 came from AE itself, and M5 and M6 originated from M1 and M2 individually. M1 and M2 (5-hydroxy aloe-emodin) and M3–M6 were also detected in rat primary hepatocytes after exposure to AE. Additionally, biliary M3, M4, and M6 were detected in ra...