Study on hepatotoxicity of different dosages of Polygoni multiflori radix praeparata in rats by metabolomics based on UPLC-Q-TOF-MS

Abstract As a kind of replenishing Chinese medicine, polygoni multiflori radix praeparata (PMP) had high application value in clinic. However, with the increase of clinical applications, more and more hepatotoxicity reports have been reported which had shown has a dose-time-toxicity dependent correlation of PMP hepatotoxicity. Therefore, it was particularly important to investigate the safe and effective dose of PMP in clinical drug administration. At the same time, reliable and sensitive biomarkers were used to characterize phenotypic biochemical disturbances in the body, thereby reflecting the hepatotoxicity mechanism caused by PMP, and providing a basis for clinical drug safety. 10, 20, and 40 g·kg -1 doses PMP were intragastricly administered to rats respectively for consecutive 28 days. serum and liver tissue were collected to measure biochemical markers using blood biochemical analyzers and observe the histopathological examination. Serum metabonomics studies were performed by UPLC-Q-TOF-MS to reveal the dose-dependent biochemical disturbances caused by PMP. Compared with the blank group, the results of biochemical analysis showed that the indicators were significantly changed in the medium dose and high dose groups. however, there was no significant difference in the low dose group. A total of 12 characteristic metabolites were obtained through metabolomic analysis. The topological analysis involved 7 metabolic pathways, resulting in significant disturbance in amino acid metabolism, energy metabolism, and bile acid metabolism. Through comprehensive histopathological examination and biochemical analysis, we concluded that the dose of 20 g·kg -1 and 40 g·kg -1 PMP water extracts lead to liver damage after taking over four weeks, and the toxicity was enhanced as the dose increased. The identification method was used to characterize the disorder of hepatic metabolism induced by PMP in a dose-dependent manner. The experimental results provided the basis for the further study of the different doses of hepatotoxicity of PMP, and also provided a warning to the clinical dosage of PMP for a long time.