Novel therapeutic potential of Serenoa repens in rat PCOS: Insights from network pharmacology and in vivo studies.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Serenoa repens dried ripe fruit has long been used in ethnomedicine to manage reproductive disorders in both men and women. While extensively investigated for benign prostatic hyperplasia, its potential in polycystic ovary syndrome (PCOS) management remains poorly explored. AIM OF THE STUDY: This study aimed to integrate network pharmacology with in vivo experimental validation to explore the efficacy and underlying mechanisms of S. repens in managing PCOS. MATERIALS AND METHODS: The chemical composition of S. repens fruit n-hexane extract was analyzed by GC/MS. Identified compounds underwent network pharmacology and KEGG/GO analyses to predict mechanisms. A letrozole-induced PCOS rat model (42 rats, 6 groups) tested the effects of S. repens extract (160, 320 mg/kg) versus control, clomiphene citrate (1 mg/kg), and commercial S. repens product known as Modern Saw Plametto (320 mg/kg). Assessments included body weight, lipid/hormonal profiles, oxidative stress (GSH, MDA), gene expression (Cyp19a1, PPARɣ), protein biomarkers (Nrf2, UCP2, HSP70), ovarian histopathology, and immunohistochemistry for AR and Ki67. RESULTS: Network pharmacology identified key interactions of S. repens constituents with targets regulating steroid hormone biosynthesis, endocrine resistance, oxidative stress, and other pathways. In vivo, oral administration of n-hexane extract of S. repens fruit improved lipid and hormonal profiles, reduced oxidative stress, normalized ovarian histology, downregulated androgen receptor (AR) expression, and restored granulosa cell proliferation in letrozole-induced PCOS rats. CONCLUSION: This study provides evidence that S. repens exerts multi-targeted therapeutic effects in PCOS, and highlights S. repens and its marketed supplements as a promising phytotherapeutic option for PCOS management.