Hepatotoxic metabolites in Polygoni Multiflori Radix— Comparative toxicology in mice

作者：Shixiao Wang, Xiang Kong, Ning Chen, Pengwei Hu, Hamza Boucetta, Zhaoliang Hu, Xin Xu, Pei Zhang, Xiang Zhan, Ming Chang, Rui Cheng, Wei Wu, Min Song, Yuting Lu, Taijun Hang · 发表于：Frontiers in Pharmacology · 年份：2022 · DOI：10.3389/fphar.2022.1007284 · 被引用次数：15 · 研究领域：Phytochemistry and biological activity of medicinal plants、Pharmacological Effects of Natural Compounds、Phytochemistry and Bioactive Compounds

Polygoni Multiflori Radix (PM) and Rhei radix et rhizoma (rhubarb) contain similar hepatocyte-toxic anthraquinones such as emodin (major free anthraquinone in PM), physcion and their glycosides. In clinical practice, PM hepatotoxicity has been widely reported, although rhubarb is not recognized as hepatotoxic. To clarify the substances basis (key components) of PM hepatotoxicity, based on the characteristic components’ similarity within PM, rhubarb and their concocted forms, a comparative sub-acute toxicity study was designed in mice. Nine groups of mice with 28 days of oral administration of these herbal extracts or 2,3,5,4′-tetrahydroxystilbene-2- O-β -D-glucoside (TSG, major and unique characteristic component in PM)-herb combinations were set as follows: Group-1, control; Group-2, PM ethanol-extract (PME); Group-3, PM praeparata ethanol-extract (PMPE); Group-4, Rhubarb ethanol-extract (RME); Group-5, Steamed rhubarb ethanol-extract (RMPE); Group-6, TSG; Group-7, PMPE-TSG combination; Group-8, RME-TSG combination; Group-9, RMPE-TSG combination. Each experimental group received an equivalent emodin dose of 29 mg/kg except for the TSG group, and an equivalent TSG dose of 1,345 mg/kg except for the PMPE, RME and RMPE groups. The results showed that PME, PMPE-TSG and RME-TSG induced liver lesions and biochemical abnormalities of liver function compared with the control. In contrast, PMPE, RME, RMPE, TSG and RMPE-TSG caused no liver lesions and fewer biochemical abnormalities. ...