Anti-inflammatory mechanism of resveratrol's Triglyceride-lowering effect in hyperlipidemia: a meta-analysis integrated network pharmacology and molecular dynamics simulation.

To elucidate resveratrol's (RES) effects on blood lipids and underlying mechanisms, this study integrated meta-analysis with network pharmacology and molecular dynamics simulations. Randomized controlled trials (RCTs) were systematically retrieved, screened, and assessed for quality, followed by meta-analysis. Separately, shared targets of RES and hyperlipidemia were identified, and protein-protein interaction networks were constructed using Cytoscape. Core targets were validated via molecular docking and 100 ns molecular dynamics simulations. Meta-analysis of seven RCTs (n = 337) revealed that RES significantly reduced triglycerides (TG) but showed no significant effects on total cholesterol, low-density lipoprotein, or high-density lipoprotein. Network pharmacology identified 794 RES-hyperlipidemia overlapping targets, with PPI analysis prioritizing three pro-inflammatory hubs: Interleukin-6 (IL6), Interleukin-1β (IL1B), and tumor necrosis factor. Molecular dynamics simulations confirmed stable RES binding to these targets, with strong binding free energies of - 13.95, - 11.86, and - 11.28 kcal/mol, respectively. RES specifically lowered TG but not other lipids, potentially through direct modulation of inflammatory pathways rather than classic lipid metabolism regulators. Comprehensive analysis indicated RES as a promising therapeutic candidate for hypertriglyceridemia.