Components synergy between stilbenes and emodin derivatives contributes to hepatotoxicity induced by <i>Polygonum multiflorum</i>
Creators: name: Zhang, Le
name: Liu, Xiaoyi
name: Tu, Can
name: Li, Chunyu
name: Song, Di
name: Zhu, Jingxiao
name: Zhou, Yuanyuan
name: Wang, Xiaohui
name: Li, Ruisheng
name: Xiao, Xiaohe
name: Liu, Youping
name: Wang, Jiabo
Publisher: name: Taylor & Francis
Year: 2019
Subjects: subject: Biochemistry
subject: Space Science
subject: Medicine
subject: Microbiology
subject: FOS: Biological sciences
subject: Cell Biology
subject: Genetics
subject: Physiology
subject: Pharmacology
subject: Environmental Sciences not elsewhere classified
subject: Chemical Sciences not elsewhere classified
subject: Immunology
subject: FOS: Clinical medicine
subject: Biological Sciences not elsewhere classified
subject: Cancer
subject: Virology

description: <i>Polygonum multiflorum</i> Thunb. (PM) is a famous traditional Chinese medicine with liver tonic effect, but arousing great concerns for hepatotoxicity issue. In this study, we elucidated the contribution of the two major compounds, emodin-8-<i>O</i>-<i>β</i>-D-glucoside (EG) and 2,3,5,4´-tetrahydroxyl diphenylethylene-2-<i>O</i>-glucoside (TSG), in PM-induced liver injury.Based on LC-MS, the two concerned compounds were detected simultaneously in the sera of patients with PM-induced liver injury. In the lipopolysaccharide (LPS)-mediated inflammatory stress rat model, by the analysis of plasma biochemistry and liver histopathology, we observed that the solo treatment of EG, not TSG, could induce significant liver injury; and the combined administration of EG and TSG caused more severe liver injury than that of EG.Metabolomics analysis revealed that the EG-triggered liver injury was associated with significant disturbances of sphingolipids and primary bile acids metabolism pathways. In the combined administration group, much more disturbances in EG-triggered metabolic pathways, as well as alterations of several additional pathways such as retinol metabolism and vitamin B6 metabolism, were observed.Taken together, we considered EG was involved in the idiosyncratic liver injury of PM, and TSG played a synergetic role with EG, which contributed to the understanding of the hepatotoxic basis of PM. <i>Polygonum multiflorum</i> Thunb. (PM) is a famous traditional Chinese medicine with liver tonic effect, but arousing great concerns for hepatotoxicity issue. In this study, we elucidated the contribution of the two major compounds, emodin-8-<i>O</i>-<i>β</i>-D-glucoside (EG) and 2,3,5,4´-tetrahydroxyl diphenylethylene-2-<i>O</i>-glucoside (TSG), in PM-induced liver injury. Based on LC-MS, the two concerned compounds were detected simultaneously in the sera of patients with PM-induced liver injury. In the lipopolysaccharide (LPS)-mediated inflammatory stress rat model, by the analysis of plasma biochemistry and liver histopathology, we observed that the solo treatment of EG, not TSG, could induce significant liver injury; and the combined administration of EG and TSG caused more severe liver injury than that of EG. Metabolomics analysis revealed that the EG-triggered liver injury was associated with significant disturbances of sphingolipids and primary bile acids metabolism pathways. In the combined administration group, much more disturbances in EG-triggered metabolic pathways, as well as alterations of several additional pathways such as retinol metabolism and vitamin B6 metabolism, were observed. Taken together, we considered EG was involved in the idiosyncratic liver injury of PM, and TSG played a synergetic role with EG, which contributed to the understanding of the hepatotoxic basis of PM.