吴茱萸碱
谷胱甘肽
药理学
化学
毒性
丁硫胺
生物化学
半胱氨酸
戒毒(替代医学)
酶
生物
医学
病理
有机化学
替代医学
作者
Kun Ren,Chuhao Zhang,Meihan Liu,Huiyuan Gao,Shumeng Ren,Dongmei Wang,Yuan Zhong,Yingni Pan,Xiaoqiu Liu
标识
DOI:10.1016/j.jep.2023.116307
摘要
As a traditional Chinese medicine and food, Euodiae Fructus (EF) is widely used in clinics to relieve pain and prevent vomiting and for making tea for more than a thousand years. In recent years, hepatotoxic reactions to EF have been reported. The intermediates produced by evodiamine and rutaecarpine metabolism in vitro were captured by glutathione (GSH), suggesting that the toxicity of EF may be related to metabolic activation. Whether licorice can inhibit the metabolic activation of EF has not been reported, which needed an effective strategy to clarify the correlation between protein conjugates and hepatotoxicity and the attenuation mechanism of licorice processing.This study aimed to explore the toxic components and mechanisms of EF based on metabolic activation and the detoxification of licorice.The content and toxicity index of protein conjugates in the liver were determined by orally administering mice and rats with EF. The attenuation mechanism of licorice was examined in cell and enzymology experiments.The change in evodiamine-cysteinylglycine (EVO-Cys-Gly) and evodiamine-cysteine (EVO-Cys) levels was consistent with the change in hepatotoxicity. Licorice inhibited the formation of the protein conjugates of EF and increased the content of GSH in L02 cells.EF mediated by P450 enzymes produced toxic intermediates, which combined with cysteine residues in animal liver and inactivate them, leading to hepatotoxicity. Interestingly, licorice can alleviate the GSH depletion caused by EF and inhibit the production of protein conjugates by inhibiting P450 enzymes.
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