Abstract
Curcumin, the primary active compound in turmeric, a widely used medicinal and edible herb in traditional Chinese medicine, exhibits beneficial effects against lipid metabolic dysfunction (LMD). Nevertheless, its comprehensive regulatory network and precise mechanisms remain unclear. In this study, network pharmacology, molecular docking, and in vitro cellular assays were integrated to elucidate the targets and mechanisms by which curcumin acts against LMD. Seven hub targets were identified: AKT1, ALB, INS, IL6, TP53, TNF, and PPARG. Kyoto Encyclopedia of Genes and Genomes analysis revealed significant enrichment of these hub targets in multiple pathways, with a notable emphasis on non-alcoholic fatty liver disease. Molecular docking confirmed that curcumin exhibited a favorable binding affinity to the hub targets. Cellular experiments using oleic acid-induced human hepatocellular carcinoma HepG2 cells demonstrated that curcumin markedly reduced triglyceride and total cholesterol levels, alleviated lipid droplet accumulation, and significantly modulated the mRNA expression of genes involved in lipid metabolism, anti-oxidant defense, and inflammation. These findings were consistent with predictions from network pharmacology. In summary, curcumin may alleviate OA-induced LMD by synergistically modulating lipid metabolism, inhibiting oxidative damage, and diminishing inflammation. This study provides a comprehensive theoretical basis for the application of curcumin in LMD intervention.