Mechanistic analysis of resveratrol in cardiac hypertrophy by network pharmacology and animal experiments

Resveratrol (Res) serves a protective role in hepatic, cardiovascular and autoimmune hypertrophic disease. However, the mechanisms by which Res ameliorates cardiac hypertrophy have not yet been fully elucidated. In the present study, network pharmacology was used to construct a network and perform enrichment analysis to evaluate the effect of Res on cardiac hypertrophy. Experimental validation was performed using 40 Sprague-Dawley rats administered intragastric 80 mg/kg/day Res and 20 mg/kg/day 3-methyladenine (3-MA) for 4 weeks. A total of 444 targets associated with cardiac hypertrophy and 229 potential disease-associated targets of Res were identified, from which 8 overlapping genes were demonstrated. Gene Ontology function and ‘Kyoto Encyclopedia of Genes and Genomes’ pathway enrichment analysis demonstrated that Res affected STAT3 and was associated with autophagy signaling pathways, including ‘negative regulation of autophagy for hypertrophic cardiomyopathy’. Furthermore, Res ameliorated isoprenaline-induced cardiac hypertrophy, significantly improving cardiac dysfunction in vivo experiment (echocardiography, the degree of ventricular hypertrophy, etc.); this effect may be associated with regulation of autophagy and apoptosis. The autophagy inhibitor 3-MA markedly reversed the anti-cardiac hypertrophy effects of Res. In conclusion, Res inhibited cardiac hypertrophy via downregulation of the apoptosis signaling pathway and upregulating the autophagy pathway.