Investigating the Molecular Mechanisms of Resveratrol in Treating Cardiometabolic Multimorbidity: A Network Pharmacology and Bioinformatics Approach with Molecular Docking Validation

Abstract

Background: Resveratrol is a potent phytochemical known for its potential in treating cardiometabolic multimorbidity. However, its underlying mechanisms remain unclear. Our study systematically investigates the effects of resveratrol on cardiometabolic multimorbidity and elucidates its mechanisms using network pharmacology and molecular docking techniques. Methods: We screened cardiometabolic multimorbidity-related targets using the OMIM, GeneCards, and DisGeNET databases, and utilized the DSigDB drug characterization database to predict resveratrol’s effects on cardiometabolic multimorbidity. Target identification for resveratrol was conducted using the TCMSP, SymMap, DrugBank, Swiss Target Prediction, CTD, and UniProt databases. SwissADME and ADMETlab 2.0 simulations were used to predict drug similarity and toxicity profiles of resveratrol. Protein–protein interaction (PPI) networks were constructed using Cytoscape 3.9.1 software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were performed via the DAVID online platform, and target-pathway networks were established. Molecular docking validated interactions between core targets and resveratrol, followed by molecular dynamics simulations on the optimal core proteins identified through docking. Differential analysis using the GEO dataset validated resveratrol as a core target in cardiometabolic multimorbidity. Results: A total of 585 cardiometabolic multimorbidity target genes were identified, and the predicted results indicated that the phytochemical resveratrol could be a major therapeutic agent for cardiometabolic multimorbidity. SwissADME simulations showed that resveratrol has potential drug-like activity with minimal toxicity. Additionally, 6703 targets of resveratrol were screened. GO and KEGG analyses revealed that the main biological processes involved included positive regulation of cell proliferation, positive regulation of gene expression, and response to estradiol. Significant pathways related to MAPK and PI3K-Akt signaling pathways were also identified. Molecular docking and molecular dynamics simulations demonstrated strong interactions between resveratrol and core targets such as MAPK and EGFR. Conclusions: This study predicts potential targets and pathways of resveratrol in treating cardiometabolic multimorbidity, offering a new research direction for understanding its molecular mechanisms. Additionally, it establishes a theoretical foundation for the clinical application of resveratrol.