Integrated Plasma and Bile Metabolomics Based on an UHPLC-Q/TOF-MS and Network Pharmacology Approach to Explore the Potential Mechanism of Schisandra chinensis-Protection From Acute Alcoholic Liver Injury

基于超高效液相色谱-四极杆/飞行时间质谱和网络药理学方法的血浆和胆汁代谢组学研究五味子对急性酒精性肝损伤的潜在保护机制

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Abstract

Schisandra chinensis (SC) is a well-known important traditional Chinese medicine (TCM) that has been used to treat liver disease in China for a long time. However, its overall effects and mechanism of action are unclear. The present study aimed to explore the potential mechanism of SC in protection against alcoholic liver injury (ALI). In this research, to enable a full assessment of metabolic changes in ALI in Sprague-Dawley rats and to increase our understanding of physiological changes in normal and pathological states, ultra-high performance liquid chromatography combined with quadrupole time of flight mass spectrometry (UHPLC-Q/TOF-MS) was used to probe potential biomarkers to learn more about ALI and to evaluate the overall effect of SC for ALI in rats. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to investigate global metabolomic alterations and to evaluate the therapeutic effects of SC in rats. The component-target-pathway network of SC was then constructed on the basis of the network pharmacology, and the liver injury-relevant signaling pathways were thus dissected and validated. The results showed that SC has conspicuous therapeutic efficacy for ALI, as suggested by the results of the pathological section and biochemical index assays, such as those for Alanine aminotransferase (ALT), Aspartate transaminase (AST), Alkaline phosphatase (AKP), γ-glutamyl transferase (γ-GT/GGT), Reactive oxygen species (ROS), and Malondialdehyde (MDA). Furthermore, 21 kinds of potential biomarkers were identified in plasma samples of ALI rats, and 20 kinds of potential biomarkers were identified in their bile samples. The biomarkers were mainly related to inflammation and dysfunctions of amino acids and energy metabolism. The recovery of these dysfunctions partly led to the curative effect of SC on ALI.

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