Schisandrin B Alleviates Lipid Metabolism Disorders and Apoptosis of MAFLD via Modulation of PPARγ-PCK1 and Caspase-3 Signaling Pathways.

Objectives: This study focuses on the regulatory mechanism of Schisandrin B (Sch B) on the lipid metabolism and apoptosis of AML-12 liver cells, with a particular emphasis on its potential therapeutic effect and mechanism of action in preventing and treating metabolic-associated fatty liver disease (MAFLD) by activating the PPARγ signaling pathway. Methods: An MAFLD cell model was established by inducing AML-12 cells with a mixture of oleic acid (OA) and palmitic acid (PA) (2:1). AML-12 cells were divided into a control group, a model group, and 20 μM and 40 μM Sch B groups. The cells were lysed and prepared into the cell suspension, then the cell suspension was centrifuged to obtain its supernatant, and the levels of total cholesterol (TC), triglycerides (TG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in the supernatant were detected according to the instructions of the kits. Effects of Sch B on the pathological changes of AML-12 cells were observed by Oil Red O staining. The key targets were screened through network pharmacology, and relevant targets were verified through molecular docking simulation. The activity of PPARγ was detected using a dual luciferase reporter plasmid, and the level of cell apoptosis was detected using the Annexin V-FITC/PI double staining method. The Western blot method was used to analyze the expression of genes related to lipid metabolism and apoptosis pathways. Results: Sch B could regulate lipid metabolism disorders in OA+PA-induced MAFLD cell model. The activation of PPARγ-PCK1/Aspase is a key step in the action of Sch B, which can effectively block fatty acid synthesis, improve fatty acid oxidation, and reduce lipid droplet aggregation in liver cells, thereby alleviating lipid metabolism abnormalities in the MAFLD cell model and inhibiting cell apoptosis. Conclusions: This finding may lay an important theoretical foundation and open a new research direction for the deep development and application of Schisandra chinensis.