Mechanism of Zhenwu Decoction Against Chronic Heart Failure with Network Pharmacology and Experimental Verification
Objective To clarify that how the Zhenwu Decoction could be against chronic heart failure(CHF)with network pharmacology and molecular docking,and to carry out experimental verification.Methods The active components and targets of Zhenwu Decoction were searched through TCMSP database;CHF related genes were retrieved through OMIM,TTD and GeneCards databases;Construct the network diagram of"compound prescription-disease-active ingredient-target".The protein interaction network of the common target of Zhenwutang and CHF was constructed by using Cytascape 3.6.0 software and STRING database.Bioconductor was used to annotate the GO function of the target protein and enrich the KEGG pathway.Use AutoDock Tools 1.5.6 software to conduct molecular docking of main components and action targets.The CHF rat model was constructed and the molecular docking results were verified by ELISA,Western blot and RT-qPCR.Results 55 active components of Zhenwu Decoction were obtained,corresponding to 84 targets,and the main compounds were β-Sitosterol,(+)-catechin,stigmasterol,osthol,3β-Acetoxyatrachnine,17 of which interact with CHF,mainly including serine/threonine protein kinase(AKT1),interleukin-6(IL-6),tumor necrosis factor(TNF),caspase-3(CASP3),peroxisome proliferator-activated receptor γ(PPARG).The functional enrichment analysis of GO and KEGG mainly involves the classic inflammation-related signal pathways such as endothelial cell proliferation,lipid metabolism regulation,IL-17 and TNF.Molecular docking shows that the main compounds have good binding ability with key targets.The experimental results showed that Zhenwu Decoction could significantly improve LVEF,LVFS,LVEDD,SV and other cardiac function indexes in CHF model rats,and reduce serum IL-6 and TNF-α Level,increased the expression level of AKT1 and PPARG mRNA and protein in myocardial tissue,and decreased the expression level of CASP3 mRNA and protei.Conclusion Zhenwu Decoction may mainly pass β-Active ingredients such as sitosterol,(+)-catechin,stigmasterol osthol act on AKT1,IL-6,TNF,CASP3,PPARG and other targets,mediate anti-inflammatory,oxidative stress,cell apoptosis and other signal pathways,and play a multi-target and multi-path synergistic therapeutic effect on CHF.
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