Abstract

Biochanin A (BCA) is a major isoflavone abundant in red clover (Trifolium pretense). The protective effect of BCA on bone loss in an ovariectomized (OVX) animal model has never been clarified. The objective of this study was to investigate the biological effects of BCA on bone loss in OVX rats in vivo and on the development of osteoblasts and osteoclasts in vitro. Ovariectomy resulted in a marked increase in body weight and a decrease in femoral bone mineral density and trabecular bone volume that was prevented by BCA or 17β-estradiol (E2) treatment. However, an increase in uterine weight was observed in E2-treated OVX rats, but not in response to BCA treatment. Treatment with BCA increased the mRNA expression of osterix, collagen type I, alkaline phosphatase (ALP), and osteocalcin and decreased the mRNA expression of tartrate-resistant acid phosphatase (TRAP) and the receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG) ratio in the femur of OVX rats. Treatment with BCA or E2 prevented the OVX-induced increase in urinary deoxypyridinoline (DPD) and serum tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β). In vitro, BCA induced preosteoblasts to differentiate into osteoblasts and increased osteoblast mineralization. BCA inhibited preosteoclasts and osteoclast proliferation and decreased osteoclast bone resorption. These findings suggest that BCA treatment can effectively prevent the OVX-induced increase in bone loss and bone turnover possibly by increasing osteoblastic activities and decreasing osteoclastic activities.

Highlights

  • Osteoporosis is the most common metabolic bone disease in women

  • Treatment of OVX rats with E2 significantly increased uterine weight compared to OVX rats (P < 0.05), but uterine weight was unchanged in Biochanin A (BCA)-treated OVX rats

  • The present study was undertaken to evaluate the effectiveness of BCA on preventing bone loss from estrogen depletion in OVX rats

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Summary

Introduction

A menopausal decline in estrogen contributes significantly to an increased rate of bone remodeling and leads to an imbalance between bone resorption and formation, eventually causing bone loss and osteoporosis [1, 2]. With increased bone resorption, can compromise bone strength, leading to a thinning of the bone structure, resulting in abnormal bone microarchitecture and reduced bone mineralization. Phytoestrogens are natural plant-derived products that have structural and functional similarities to estradiol. They are considered to be a safe alternative to hormone replacement therapy (HRT) [3] and are used in phytomedicine to treat menopausal symptoms and osteoporosis. We suggested that BCA may have benefits to osteoporosis resulted from estrogen decline

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