TY - JOUR T1 - Multiomics Profiling Reveals Protective Function of <em>Schisandra</em> Lignans against Acetaminophen-Induced Hepatotoxicity JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 1092 LP - 1103 DO - 10.1124/dmd.120.000083 VL - 48 IS - 10 AU - Caixia Yan AU - Huimin Guo AU - Qingqing Ding AU - Yuhao Shao AU - Dian Kang AU - Tengjie Yu AU - Changjian Li AU - Haoran Huang AU - Yisha Du AU - He Wang AU - Kangrui Hu AU - Lin Xie AU - Guangji Wang AU - Yan Liang Y1 - 2020/10/01 UR - http://dmd.aspetjournals.org/content/48/10/1092.abstract N2 - The action principles of traditional Chinese medicines (TCMs) feature multiactive components, multitarget sites, and weak combination with action targets. In the present study, we performed an integrated analysis of metabonomics, proteomics, and lipidomics to establish a scientific research system on the underlying mechanism of TCMs, and Schisandra lignan extract (SLE) was selected as a model TCM. In metabonomics, several metabolic pathways were found to mediate the liver injury induced by acetaminophen (APAP), and SLE could regulate the disorder of lipid metabolism. The proteomic study further proved that the hepatoprotective effect of SLE was closely related to the regulation of lipid metabolism. Indeed, the results of lipidomics demonstrated that SLE dosing has an obvious callback effect on APAP-induced lipidic profile shift. The contents of 25 diglycerides (DAGs) and 21 triglycerides (TAGs) were enhanced significantly by APAP-induced liver injury, which could further induce liver injury and inflammatory response by upregulating protein kinase C (PKCβ, PKCγ, PKCδ, and PKCθ). The upregulated lipids and PKCs could be reversed to the normal level by SLE dosing. More importantly, phosphatidic acid phosphatase, fatty acid transport protein 5, and diacylglycerol acyltransferase 2 were proved to be positively associated with the regulation of DAGs and TAGs.SIGNIFICANCE STATEMENT Integrated multiomics was first used to reveal the mechanism of APAP-induced acute liver failure (ALF) and the hepatoprotective role of SLE. The results showed that the ALF caused by APAP was closely related to lipid regulation and that SLE dosing could exert a hepatoprotective role by reducing intrahepatic diglyceride and triglyceride levels. Our research can not only promote the application of multicomponent technology in the study of the mechanism of traditional Chinese medicines but also provide an effective approach for the prevention and treatment of ALF. ER -