UPLC/MS/MS-Based Metabolomics Study of the Hepatotoxicity and Nephrotoxicity in Rats Induced by Polygonum multiflorum Thunb.

作者：Yan Yan, Ning Shi, Xuyang Han, Guodong Li, Binyu Wen, Jian Gao · 发表于：ACS Omega · 年份：2020 · DOI：10.1021/acsomega.0c00647 · 被引用次数：33 · 研究领域：Phytochemistry and biological activity of medicinal plants、Drug-Induced Hepatotoxicity and Protection、Pharmacological Effects of Natural Compounds

Thunb. (PM) is one of the most frequently used natural products in China. Its hepatotoxicity has been proven and reported. However, chronic PM toxicity is a dynamic process, and a few studies have reported the long-term hepatotoxic mechanism of PM or its nephrotoxicity. To elucidate the mechanism of hepatotoxicity and nephrotoxicity induced by PM after different administration times, different samples from rats were systematically investigated by traditional biochemical analysis, histopathological observation, and nontargeted metabolomics. The concentrations of direct bilirubin (DBIL) at 4 weeks and total bile acid, DBIL, uric acid, and blood urea nitrogen at 8 weeks were significantly increased in the treatment group compared with those in the control group. Approximately, 12 metabolites and 24 proteins were considered as unique toxic biomarkers and targets. Metabolic pathway analysis showed that the primary pathways disrupted by PM were phenylalanine and tyrosine metabolism, which resulted in liver injury, accompanied by chronic kidney injury. As the administration time increased, the toxicity of PM gradually affected vitamin B6, bile acid, and bilirubin metabolism, leading to aggravated liver injury, abnormal biochemical indicators, and marked nephrotoxicity. Our results suggest that the hepatotoxicity and nephrotoxicity caused by PM are both dynamic processes that affect different metabolic pathways at different administration times, which indicated that PM-induced liver ...