Molecular mechanism of isoflavone aglycoside compounds in suppressing endometriosis progression

Purpose: To assess the potential therapeutic efficacy of isoflavone aglycones in suppressing endometriosis progression through multi-pathway targeting. Methods: Using molecular docking simulations, the interactions between genistein, daidzein, and glycitein, with estrogen receptor α (ERα), estrogen receptor β (ERβ), Tumor Necrosis Factor-α receptor (TNF-α), Nuclear Factor-κappa Beta receptor (NF-κB), and prostaglandin EP3 receptor were analyzed and compared to dienogest, a standard treatment. Results: Results indicated that genistein and daidzein showed strong binding affinities to estrogen receptor β, with scores of -8.7 kcal/mol, surpassing dienogest (-8.5 kcal/mol). Glycitein exhibited the highest among other isoflavone aglycones binding affinity to the prostaglandin EP3 receptor (-9.2 kcal/mol), suggesting its potential in reducing inflammation and proliferation in endometriosis. Additionally, glycitein demonstrated the strongest interaction with NF-κB (-6.4 kcal/mol), a key regulator of inflammation and cell survival in endometriosis. Conclusion: The findings suggest that isoflavone aglycones, particularly genistein, daidzein, and glycitein, could serve as effective therapeutic agents for endometriosis by targeting multiple pathways involved in the pathogenesis of endometriosis. Further clinical studies are needed to validate their efficacy and safety in treating endometriosis while preserving reproductive function.