Mechanism of Action of Cinnamic Acid in Treatment of Chronic Heart Failure:A Study Based on Network Pharmacology and Experimental Validation
Objective To investigate the potential targets and mechanism of action of cinnamic acid in the treatment of chronic heart failure (CHF)based on network pharmacology,molecular docking,and invitro experimental validation.Methods On-line databases of network pharmacology were used to predict the targets of cinnamic acid and CHF,and the intersecting targets were used to construct a protein-protein interaction network in String database.Cytoscape 3 .7 .2 software was used to perform a visual analysis and obtain the core targets,and Metascape database was used to perform gene ontology (GO)and Kyoto En-cyclopedia of Genes and Genomes (KEGG)enrichment analyses and predict the mechanism of action of cinnamic acid in the treatment of CHF.Molecular docking and invitro experiment were used to validate the above results.Results Network phar-macology analysis obtained 187 potential targets of cinnamic acid,which were intersected with 6094 disease targets of CHF, and 132 intersecting targets were obtained,involving 10 core targets such as CASP3,JUN,PTGS2,MMP9,and TLR4.GO and KEGG enrichment analyses showed that cinnamic acid was associated with the biological processes such as cellular response to reactive oxygen species (ROS)and cellular response to oxidative stress and was involved in the signaling pathways including cell apoptosis.Molecular docking showed that cinnamic acid had good binding activity to 10 core targets.The invitro experi-ment showed that cinnamic acid significantly reduced the apoptosis rate of H9c2 cardiomyocytes,the level of ROS (P<0.05), the mRNA expression levels of c-Jun,PTGS2,MMP9,and TLR4 (P<0.05),and the protein expression levels of caspase-9, caspase-3,and Bax (P<0.05),and it significantly increased the protein expression level of Bcl-2 (P<0.05).After the appli-cation of N-acetylcysteine (NAC),there were significant reductions in cell apoptosis rate,ROS level,and the protein expres-sion level of Bax (P<0.05)and a significant increase in the protein expression level of Bcl-2 (P<0.05),suggesting that NAC had a similar effect to cinnamic acid.Conclusion The above research findings show that cinnamic acid exerts a therapeutic effect on CHF by regulating multiple signals and targets and inhibiting oxidative stress injury and cell apoptosis of cardiomyo-cytes,which is one of the important material bases for Linggui Zhugan Decoction in the prevention and treatment of CHF.
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维普
