Elucidating the Molecular Mechanisms of Vitex negundo L. in Polycystic Ovary Syndrome via Metabolomics-Driven Network Pharmacology.

Polycystic ovary syndrome (PCOS) is a hormonal disorder marked by irregular menstrual cycles, elevated androgen levels, ovarian cysts, hirsutism, acne and other symptoms. While conventional medications such as Metformin and Spironolactone are commonly prescribed, they are often associated with undesirable side effects. As a result, there is growing interest in alternative treatments, particularly those involving medicinal plants. Vitex negundo L., a member of the Lamiaceae family, has demonstrated promising therapeutic effects against PCOS. However, its precise molecular mechanism of action remains unclear. To explore this, we conducted an untargeted metabolomics analysis using UPLC-MS/MS to identify bioactive compounds, followed by network pharmacology to elucidate potential mechanisms. Metabolite fingerprinting revealed 186 metabolites, among which 122 were identified as secondary metabolites. Network pharmacology analysis uncovered 910 potential targets associated with the identified compounds and 297 known PCOS-related disease targets, with 50 overlapping targets between the two datasets. Key hub targets identified included P53, ESR1, AKT1, STAT3, CTNNB1, ERBB2, BCL2, EGFR, MTOR and IL6. Furthermore, molecular docking highlighted several bioactive constituents-syringin, 4-(3,4-dihydroxyphenyl)-6,7-dihydroxynaphthalene-2-carboxylic acid, and Isovitexin-as potential lead compounds for PCOS treatment. Further evaluation of lead compounds can be conducted through in vitro and in vivo studies.