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Chemical Reactivity of Emodin and Its Oxidative Metabolites to Thiols

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journal contribution
posted on 16.11.2016, 00:00 by Boyang Qin, Yang Xu, Jiaming Chen, Wenlin Huang, Ying Peng, Jiang Zheng
Polygonum multi­florum is an herbal medicine widely employed in China. Hepato­toxicity of the herbal medicine has been well documented, but the mechanisms of the toxicity remain unknown. Emodin (EM) is a major constituent of the herb and has been reported to be hepato­toxic. The main purpose of this study was to define the metabolic pathways of EM in order to characterize the potential reactive intermediates. EM was incubated with rat liver microsomes or human liver microsomes, followed by LC-MS/MS analysis to investigate the in vitro and in vivo metabolism of EM. As a result, three mono­hydroxylation metabolites (M1–M3) were detected after exposure to EM: ω-hydroxy­emodin, 2-hydroxy­emodin, and 5-hydroxy­emodin. Urinary M1 and M2 were detected in rats administered EM. Three mercapturic acids (M4–M6) were found in microsomal incubations containing EM, NADPH, and N-acetyl­cysteine. It appears that M4 originated from parent compound EM, and M5 and M6 originated from M1 and M2, respectively. Two biliary EM-derived GSH conjugates were found in EM-treated rats. One arose from direct adduction of EM with GSH, and the other was derived from M1. Cytochrome P450’s 1A2, 2C19, and 3A4 were the predominant P450 enzymes to oxidize EM. The findings helped us to understand the mechanisms of EM-induced hepato­toxicity.

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