Mechanism of Yugeng Tongyu Decoction for Treating Angina Pectoris Based on Network Pharmacology Combined with Molecular Dynamics Simulation Technique
Objective:Mechanism of Yugeng Tongyu decoction for treating angina pectoris was studied through network pharmacology,molecular docking and molecular dynamics simulation techniques. Methods:By searching the traditional Chinese medicine ( TCM) system pharmacology database(TCMSP) and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP) traditional Chinese medicine component databases,the chemical components and corresponding protein targets of Yugeng Tongyu decoction were screened,and the gene names were further queried through UniProt database.According to the query results of the database,the interaction network of "TCM-active ingredient-target" was constructed. At the same time,the disease-related targets of angina pectoris were screened through GeneCards and Online Mendelian Inheritance in Man ( OMIM) disease target databases,and the target of Yugeng Tongyu decoction were intersected with the target of angina pectoris disease to obtain the common target. The "active ingredient-potential target" and "drug-target-gene ontology ( GO )/Kyoto Encyclopedia of Genes and Genomes (KEGG) " network diagrams were constructed by Cytoscape and STRING databases respectively.AutoDock Vina was used for molecular docking verification. OpenMM software were used to simulate and verify the protein-ligand system after molecular docking.Finally,it was verified by cell experiments in vitro.Results:A total of 265 active ingredients and 671 potential targets were obtained.Further,182 signal pathways were screened. GO enrichment analysis showed that it mainly involves in inflammatory reactions,tissue repair,oxidative stress reactions.KEGG enrichment analysis showed that it mainly involved atherosclerosis,diabetes complications and non-alcoholic fatty liver disease related pathways. The results of molecular docking showed that the minimum binding energy of 10 pairs of key active ingredients and core target was less than-5.0 kJ/mol,which was smaller than the binding energy of the primary ligand of the target,indicating better docking effect.Molecular dynamics simulation showed that ginsenoside Rh2 and phosphatidylinositol-3-kinase catalytic subunit α( PIK3CA) showed better binding stability and activity. In vitro cell experiments showed that ginsenoside Rh2 showed obvious myocardial protective effect and activated the phosphatidylinositol 3-kinase ( PI3K)-protein kinase B(AKT) pathway.Conclusion:Through network pharmacology,it was predicted that Yugeng Tongyu decoction might be composed of quercetin,luteolin,kaempferol,isoflavone,baicalein,cryptotanshinone,aloe emodin,ginsenoside Rh2,corydaline,fumarine monophenol,and other key active ingredients.The regalation of hypoxia inducible factor-1(HIF-1),tumor necrosis factor(TNF),PIK3CA,estrogen receptor 1(ESR1) and other potential pathway targets were most closely related to inflammation and oxidative stress in metabolic diseases.Through molecular docking,molecular dynamics simulation and cell experiments,the pharmacological effects of ginsenoside Rh2 were closely related to the activation of PIK3-AKT pathway.The results suggest that the anti-inflammatory effect may be one of the potential mechanisms of Yugeng Tongyu decoction for the treatment of angina pectoris.
万方数据
维普
