Network pharmacology integrated with pharmacological evaluation for investigating the mechanism of resveratrol in perimenopausal depression

Perimenopause constitutes a pivotal transitional phase characterized by hormonal variability and heightens vulnerability to depressive episodes. This study seeks to elucidate the mechanism of resveratrol (RES) in perimenopausal depression through integrated network pharmacology, molecular docking analysis, and experimental validation. Screening yielded 83 RES-related disease targets, with IL10, CCL2, and SERPINE1 identified as core genes overexpressed in perimenopausal depression. GO analysis and KEGG pathway enrichment analysis predicted that the target genes could regulate the PI3K-Akt, FoxO, HIF-1, and IL-17 signaling pathways. Molecular docking indicated SERPINE1 as a promising RES target. Consistently, in vitro experiments showed that RES significantly attenuated the inflammatory response and apoptosis of lipopolysaccharide-stimulated CTXTNA2 cells. RES also reduced the expression of NLRP3, caspase-1, SERPINE1 proteins and acetylation, while increasing the expression of BDNF, TrkB, SIRT1, and decreasing MAO-A proteins. In vivo experiments demonstrated that RES also significantly improved the depression behaviors, increased the levels of 5-HT1A and SIRT1, and decreased levels of MAO-A of depression rats. This study unveils RES's potential targets and mechanism in perimenopausal depression, laying groundwork for future research.