Therapeutic Evaluation of Hydroalcoholic Extract of Luffa cylindrica in Letrozole Induced Polyendocrine Metabolic Ovarian Syndrome (PMOS): An Integrated In Silico, In Vitro and In Vivo Approach
Polyendocrine Metabolic Ovarian Syndrome; Luffa cylindrica; Letrozole; Network Pharmacology; Molecular Docking; In Vivo; PMOS; Phytotherapy
AuthorsAbstractPurpose: Polyendocrine Metabolic Ovarian Syndrome (PMOS), recently renamed from Polycystic Ovary Syndrome (PCOS) through international consensus, is a multisystem endocrine and metabolic disorder affecting an estimated 170 million women globally. Current pharmacological treatments carry significant adverse effects, necessitating exploration of safer, plantbased therapeutic alternatives. This study aimed to evaluate the therapeutic efficacy of a hydroalcoholic extract of Luffa cylindrica (LCE) against PMOS through an integrated in silico, in vitro, and in vivo approach. Methods: Active phytochemicals of LCE were identified by liquid chromatography–mass spectrometry (LCMS). Network pharmacology and molecular docking studies using Schrödinger Glide were performed to identify PMOSrelevant molecular targets and key signalling pathways. In vitro enzyme inhibition assays evaluated alphaamylase and alphaglucosidase inhibitory activity. For in vivo assessment, a letrozoleinduced PMOS rat model was established, and female Wistar rats were treated orally for 14 days with metformin (20 mg/kg) as a positive control or LCE at doses of 100, 200, and 400 mg/kg following 21 days of letrozole induction. Results: LCMS profiling identified key phytochemicals including Rutin, Luteolin, Apigenin, Quercetin, and Neodiosmin. In vitro studies demonstrated potent inhibitory activity against alphaamylase (IC₅₀: 80.45 µg/mL) and alphaglucosidase (IC₅₀: 56.58 µg/mL), indicating significant postprandial glycaemic regulation potential. Network pharmacology identified 46 PMOSrelevant molecular targets across 16 key signalling pathways, including PI3KAkt, Estrogen, Ras, and MAPK cascades. Molecular docking revealed significantly superior binding affinities of LCE phytocompounds over metformin at EGFR, ESR2, and IGF1R. In vivo, LCE produced dosedependent restoration of estrous cyclicity, hormonal balance, lipid profiles, fasting blood glucose levels, antioxidant status, and ovarian histopathological architecture Conclusion: LCE demonstrates promising multitarget therapeutic potential for PMOS management, modulating key metabolic, hormonal, and ovarian pathways. These findings support Luffa cylindrica as a rational phytotherapeutic candidate warranting further clinical investigation.
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