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

**Authors:** Jeong-Won Ahn, Hyun-Soo Kim, Kongara Damodar, Hee-Hyun Shin, Kyung-Mi Kim, Jung-Youl Park, Yeong-Min Yoo, Jae-Chul Jung, Seong-Soo Joo

PMC · DOI: 10.3390/molecules30102218 · 2025-05-20

## TL;DR

This study shows that sophoricoside and genistein from S. japonicum fruit can help manage postmenopausal symptoms like bone loss and inflammation, offering a safer alternative to hormone therapy.

## Contribution

The study demonstrates the therapeutic benefits of sophoricoside and its aglycone form in managing postmenopausal symptoms with a favorable safety profile.

## Key findings

- Both sophoricoside and genistein reduced weight gain and vaginal dryness in ovariectomized rats.
- The treatments preserved bone integrity by modulating RANKL and TGF-β and suppressed inflammation in adipose tissue.
- They regulated adipogenesis markers more effectively than 17β-estradiol and showed no adverse effects on organ weight.

## Abstract

This study investigates the therapeutic potential of sophoricoside and its aglycone metabolite, genistein, derived from Styphnolobium japonicum L. fruit, as natural alternatives to hormone replacement therapy for postmenopausal symptom management. Using Lactobacillus plantarum 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 S. japonicum L. fruit-derived phytoestrogens as promising candidates for the comprehensive management of postmenopausal symptoms, offering an efficacious and safer alternative to conventional hormone therapy.

## Linked entities

- **Genes:** TNFSF11 (TNF superfamily member 11) [NCBI Gene 8600], TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040], FABP4 (fatty acid binding protein 4) [NCBI Gene 2167], Klf15 (Kruppel-like factor 15) [NCBI Gene 31410], lepa (leptin a) [NCBI Gene 106561227], PPARG (peroxisome proliferator activated receptor gamma) [NCBI Gene 5468]
- **Chemicals:** sophoricoside (PubChem CID 5321398), genistein (PubChem CID 5280961), 17β-estradiol (PubChem CID 154274), IL-6 (PubChem CID 165368475)

## Full-text entities

- **Diseases:** vaginal dryness (MESH:D014627), Inflammation (MESH:D007249), weight gain (MESH:D015430)
- **Chemicals:** Sophoricoside (MESH:C120642), genistein (MESH:D019833), Aglycone (MESH:C458179), AG (MESH:D012834), Isoflavone Glycoside (-), 17β-estradiol (MESH:D004958), glycoside (MESH:D006027)
- **Species:** Lactiplantibacillus plantarum (species) [taxon 1590], Styphnolobium japonicum (Japanese pagoda tree, species) [taxon 3897], Rattus norvegicus (brown rat, species) [taxon 10116], S. japonicum [taxon 349478]

## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12113653/full.md

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Source: https://tomesphere.com/paper/PMC12113653