Systems Pharmacology and Multitarget Modulation of Letrozole-HFD-Induced Polycystic Ovarian Syndrome by Fruit Pulp of Prunus armeniaca.

Polycystic ovary syndrome (PCOS) is a multifactorial endocrine-metabolic disorder characterized by hyperandrogenism, insulin resistance, oxidative stress, and chronic inflammation. The present study investigated the multitarget pharmacological effects of hydroalcoholic extract of fruit pulp of Prunus armeniaca (HAE of FPPA) in a letrozole-high-fat diet (HFD)-induced PCOS model using integrated network pharmacology, ADMET profiling, molecular docking, and experimental validation. Intersection analysis identified 105 common targets between major FPPA phytoconstituents and PCOS-associated proteins, with enrichment of PI3K/Akt, MAPK, HIF-1, endocrine resistance, and inflammatory signaling pathways. Docking analysis demonstrated strong interactions of rutin, chlorogenic acid, and catechin with selected network-prioritized PCOS-associated proteins involved in insulin signaling, inflammation, and steroidogenesis. In vivo, HAE of FPPA dose-dependently restored estrous cyclicity, normalized LH/FSH ratio and testosterone levels, improved insulin resistance, β -cell function, and dyslipidemia, and reduced lactate dehydrogenase activity and atherogenic index. FPPA further attenuated ovarian oxidative stress through suppression of lipid peroxidation and restoration of GSH, GPx, GR, and SOD levels, accompanied by marked recovery of ovarian histoarchitecture with reduced cystic follicles and reappearance of corpus luteum. Collectively, this study provides the first integrated experimental and systems pharmacology evidence supporting FPPA as a promising multitarget phytotherapeutic candidate for hyperandrogenic and metabolically driven PCOS.