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1074
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Network Pharmacology Analysis of Phytochemicals Targeting PCOS-Associated Genes: A Bioinformatics Approach to Therapeutic Intervention
نویسندگان
Reza Fani Kisomi - Farhad Mashayekhi
چکیده
Abstract Objective: Dysregulation of the miR-200b/ZEB axis and PI3K signaling plays a critical role in polycystic ovary syndrome (PCOS) pathophysiology. This study aimed to identify therapeutic phytochemicals targeting these pathways using network pharmacology. Methodology: A compound-target network was constructed by integrating 8 bioactive phytochemicals with key PCOS-associated genes (ESR1, ESR2, PIK3CA) using STITCH/STRING databases and Cytoscape software. High-confidence interactions (Combined Score ≥ 0.7) were filtered, and literature-based curation (2023–2025) was integrated to map the regulatory feedback loop involving hsa-miR-200b-3p. Results: The analysis revealed 14 high-confidence compound-gene interactions (mean score: 0.831). Genistein demonstrated the highest binding affinity to estrogen receptors (ESR1/ESR2 score: 0.996), validating a direct phytoestrogenic mechanism. Network topology analysis uncovered a hierarchical targeting pattern where phytochemicals primarily activate ESR hubs, subsequently modulating downstream ZEB1/ZEB2 effectors and the PI3K pathway. The integrated model elucidates a novel mechanism wherein multi-target phytochemicals restore the miR-200b double-negative feedback loop, offering a systems-level rationale for herbal therapeutic interventions in improving PCOS reproductive outcomes.
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