Exploring the mechanism of Cassiae semen in regulating lipid metabolism through network pharmacology and experimental validation

• Published in: Bioscience reports 2023-02, Vol.43 (2), p.1
• Main Authors: Huang, Lili, Zhu, Haiyan, Tang, Yuqin, Luo, Zheng, Xia, Luyun, Zhang, Chunjiang, Wang, Yanqiu, Huai, Wenying, Fang, Zhiyan, Li, Shenrong, Yan, Zhiyong, Yin, Qiaozhi, Zhang, Tian-E
• Format: Article
• Language: English
• Subjects: Accumulation; Amyloid beta-Peptides; Amyloid precursor protein; Bioinformatics; Caspase 3; Chinese medicine; Class I Phosphatidylinositol 3-Kinases; Down-regulation; Drugs, Chinese Herbal - pharmacology; Epidermal growth factor receptors; ErbB Receptors; Ethanol; Fatty liver; Genes; Growth factors; Herbal medicine; Humans; Hyperlipidemia; Intracellular signalling; Kinases; Lipid Metabolism; Lipids; Liver diseases; MAP kinase; Medical research; Metabolism; Molecular Bases of Health & Disease; Molecular docking; Molecular Docking Simulation; Network Pharmacology; Non-alcoholic Fatty Liver Disease - drug therapy; Non-alcoholic Fatty Liver Disease - genetics; Pharmacology; Phosphatidylinositol 4,5-diphosphate; Plant extracts; Proteins; Quinizarin; R&D; Regulatory mechanisms (biology); Research & development; Seeds; Signal transduction; Signaling; Software; Therapeutic targets; Traditional Chinese medicine
• ISSN: 0144-8463; 1573-4935
• DOI: 10.1042/BSR20221375

Multiple studies have assessed the role of Cassiae semen (CS) in regulating lipid metabolism. However, the mechanism of action of CS on non-alcoholic fatty liver disease (NAFLD) has seen rare scrutiny. The objective of this study was to explore the regulatory mechanism of CS on lipid metabolism in NAFLD. Components of CS ethanol extract (CSEE) were analyzed and identified using UPLC-Q-Orbirap HRMS. The candidate compounds of CS and its relative targets were extracted from the Traditional Chinese Medicine Systems Pharmacology, Swiss-Target-Prediction, and TargetNet web server. The Therapeutic Target Database, Genecards, Online Mendelian Inheritance in Man, and DisGeNET were searched for NAFLD targets. Binding affinity between potential core components and key targets was established employing molecular docking simulations. After that, free fatty acid (FFA)-induced HepG2 cells were used to further validate part of the network pharmacology results. Six genes, including Caspase 3 (CASP3), phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit α (PIK3CA), epidermal growth factor receptor (EGFR), and amyloid β (A4) precursor protein (APP) were identified as key targets. The mitogen-activated protein kinase (MAPK) signaling pathway was found to associate closely with CS's effect on NAFLD. Per molecular docking findings, toralactone and quinizarin formed the most stable combinations with hub genes. About 0.1 (vs. FFA, P