基于网络药理学、分子对接和实验验证探究山楂-泽泻药对治疗高甘油三酯血症的作用机制OA

Objective:To systematically explore the mechanism of action of hawthorn-Alisma herb in the treatment of hypertriglyceridemia based on network pharmacology,molecular docking and in vitro experiments.Methods:Poten-tial active ingredients and their targets of hawthorn and alisma were obtained using a traditional Chinese medicine sys-tems pharmacology database and analysis platform and a TCM integrated pharmacology research platform 2.0.Targets related to hypertriglyceridemia were retrieved from the Gene Cards database,and an"active ingredient-target-disease"network was constructed using Cytoscape 3.7.2 software.Common targets from both were input into the STRING data-base to obtain a protein-protein interaction network.GO functional enrichment analysis and KEGG pathway enrich-ment analysis were performed using the R package clusterProfiler.Molecular docking verification was performed using Autodock Vina 1.2.2.Six monomers of traditional Chinese medicine with good binding ability were selected for experi-mental verification.An AML-12 hyperlipidemic cell model was constructed to investigate the effects of the monomers of traditional Chinese medicine on lipid droplet deposition and lipolysis in the hyperlipidemic cell model.Results:The hawthorn-alisman pair was screened and identified 19 potential active ingredients and 246 potential targets,of which 94 were co-targets of hypertriglyceridemia.GO functional enrichment analysis revealed that the hawthorn-alisman pair's treatment of hypertriglyceridemia is mainly related to its response to lipopolysaccharide,gene transcription,and expression.KEGG pathway enrichment analysis showed that it is mainly related to fluid shear stress and atherosclerosis pathways,as well as the AGE-RAGE signaling pathway in diabetic complications.Molecular docking results showed that the main active ingredients,kaempferol,quercetin,alismol B,alismol B acetate,alismol C acetate,and alismol B acetate,have strong binding forces with multiple pathway molecules.Experimental results showed that alismol B,kaempferol,and alismol C acetate can significantly reduce lipid droplet deposition in hyperlipidemia cells and regu-late triglyceride lipase to enhance lipolysis.Conclusion:The hawthorn-Alisma herbal pair treats hypertriglyceridemia through synergistic effects involving multiple components,targets,and pathways,providing theoretical basis and exper-imental support for the lipid-lowering mechanism and rational clinical application of the hawthorn-Alisma herbal pair.