Identification of Potential Mechanisms of Jiangtang Tiaozhi Formula in Improving Glycolipid Metabolism Disorder Based on Network Pharmacology and Experimental Verification
- VernacularTitle:基于网络药理学和实验验证鉴定降糖调脂方改善糖脂代谢紊乱的关键靶点及作用机制
- Author:
Xinyi FANG
1
;
Mingzhe ZHANG
;
Jiaxing TIAN
;
Xiaolin TONG
Author Information
- Publication Type:Journal Article
- Keywords: Jiangtang Tiaozhi Formula; Glycolipid metabolism disorder; Network pharmacology; Molecular docking; Molecular dynamics simulation; Lipid and atherosclerotic pathway
- From: World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(9):2536-2552
- CountryChina
- Language:Chinese
- Abstract: Objective Jiangtang Tiaozhi Formula(JTTZF)is highly effective in improving glycolipid metabolism disorder.However,its exact mechanism of action has not been fully elucidated.This study aims to explore the potential targets and mechanisms of JTTZF in improving glycolipid metabolism disorder through network pharmacology,molecular docking,molecular dynamics simulations,and experimental validation.Methods Glycolipid metabolism disorder-related targets were obtained from the GeneCards database,while the relevant action targets of the main active ingredients of JTTZF were obtained from the CTD and SwissTargetPrediction databases.Protein-protein interaction(PPI)networks were constructed using STRING and Cytoscape.After selecting the potential key targets,Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were conducted through the Metascape database,and a network map of"herb-active ingredient-target-pathway"was constructed.Molecular docking was carried out using AutoDock vina and PyMOL software to verify the correlation between the main components of JTTZF and the core targets.Molecular dynamics simulation was conducted for optimal core protein-compound complexes obtained by molecular docking.A mouse glycolipid metabolism disorder model was established,and the results of network pharmacology were verified by in vivo experiments.Results Topological analysis of the PPI network revealed ten core targets,including TNF,CTNNB1,AKT1,NF-κB1,ESR1,FN1,TP53,IL-1β,IL-6,and EGFR.GO functional enrichment analysis showed that these targets were mainly related to signal transduction and transcriptional regulation.KEGG pathway analysis showed that these targets were related to lipid and atherosclerosis pathway.Molecular docking results reported that the core active ingredient of JTTZF has a certain binding affinity with AKT1,FN1,and IL-6.Molecular dynamics simulations revealed good binding ability between lovastatin,coptisine,salvianolic acid B,and AKT1.Animal experiments showed that JTTZF may reduce blood glucose and blood lipid levels and improve glycolipid metabolism disorder by down-regulating the expression of AKT1,TP53,and inflammatory regulators in lipid and atherosclerotic pathway,inhibiting the expression of FN1 and EGFR,and increasing the expression of CTNNB1 and ESR1.Conclusion JTTZF participates in the regulation of lipid and atherosclerotic pathway,and comprehensively regulates glucose and lipid metabolism and improves atherosclerotic lesions,thereby preventing and treating the occurrence and development of glycolipid metabolism disorder and its complications.
