Therapeutic Advantages of Isoflavone Glycoside and Aglycone Forms of Sophoricoside in the Amelioration of Postmenopausal Symptoms: Bone Health, Metabolic Regulation, and Systemic Inflammation

This study investigates the therapeutic potential of sophoricoside and its aglycone metabolite, genistein, derived from <i>Styphnolobium japonicum</i> L. fruit, as natural alternatives to hormone replacement therapy for postmenopausal symptom management. Using <i>Lactobacillus plantarum</i> to model intestinal biotransformation, we compared glycoside-rich (Rex) and aglycone-rich (Rex-AG) extracts in ovariectomized rats. Both treatments significantly reduced weight gain and alleviated vaginal dryness, with Rex demonstrating superior thermoregulatory stabilization. Histological and molecular analyses revealed preserved trabecular bone integrity through the downregulation of RANKL and upregulation of TGF-β. Both extracts exhibited potent anti-inflammatory effects in adipose tissue, suppressing IL-6 and TNF-α, while regulating adipogenesis markers (FABP4, KLF, leptin, PPARγ) more effectively than 17β-estradiol. Serum genistein concentrations confirmed its efficient biotransformation and systemic bioavailability. Importantly, the treatments showed favorable safety profiles with no adverse effects on organ weight. These findings establish <i>S. japonicum</i> L. fruit-derived phytoestrogens as promising candidates for the comprehensive management of postmenopausal symptoms, offering an efficacious and safer alternative to conventional hormone therapy.