Abstract
Danggui Buxue Tang (DBT), a traditional Chinese Medicine decoction containing Astragali Radix (AR) and Angelicae Sinensis Radix (ASR), is commonly prescribed for women in China as a remedy for menopausal symptoms. Previous study indicated that DBT stimulated cell growth and differentiation of human osteosarcoma MG-63 cells and exhibited estrogenic properties via estrogen receptors (ERs). The present study aimed to study the bone protective effects of DBT and its potential interactions with selective estrogen receptor modulators (SERMs, tamoxifen and raloxifene) in both in vivo and in vitro models as they act via similar ERs. Six-month-old Sprague-Dawley rats were randomly assigned to the following treatments for 12 weeks: (1) sham-operated control group with vehicle (sham), (2) ovariectomized group with vehicle (OVX), (3) OVX with 17β-estradiol (E2, 2.0 mg/kg day), (4) OVX with tamoxifen (Tamo, 1.0 mg/kg day), (5) OVX with raloxifene (Ralo, 3.0 mg/kg day), (6) OVX with DBT (DBT, 3.0 g/kg day), (7) OVX with DBT+Tamoxifen (DBT+Tamo), and (8) OVX with DBT+Raloxifene (DBT+Ralo). Effects of DBT and potential interactions between DBT and SERMs were also evaluated in MG-63 cells. DBT, tamoxifen, raloxifene, and their combinations significantly increased bone mineral density (BMD) and improved trabecular bone properties, including bone surface (BS), trabecular bone number (Tb.N), and trabecular bone separation (Tb.Sp), as well as restored changes in bone turnover biomarkers and mRNA expression of genes involved in bone metabolism in OVX rats. Furthermore, DBT, SERMs, and their combinations significantly increased serum estradiol and suppressed follicle stimulating hormone and luteinizing hormone in OVX rats, suggesting the possible involvement of the hypothalamus–pituitary–gonadal axis in mediating their bone protective effects. However, SERMs, but not DBT, significantly increased uterus index in OVX rats. DBT significantly induced ALP activity and estrogen response element-dependent transcription in MG-63 cells. Our study demonstrated that DBT alone and in combinations with SERMs could exert bone protective effects in vitro and in vivo.
Highlights
Postmenopausal osteoporosis is a metabolic bone disease characterized by decreased bone mineral density (BMD) and increased bone fragility, resulting from the rapid drop of endogenous estrogen level that is experienced by 40% of postmenopausal women (Stein et al, 2014)
Our results showed that Danggui Buxue Tang (DBT) in combination with tamoxifen and raloxifene significantly reduced IL-6 mRNA expression in femoral head of OVX rats (p < 0.01 vs. OVX). mRNA expression of genes involved in bone metabolism in femoral head in OVX rats treated with SERMs alone was not statistically different from those in OVX rats treated with respective SERMs in combination with DBT
Danggui Buxue Tang at 3 g/kg day is effective in protecting against bone loss associated with estrogen deficiency
Summary
Postmenopausal osteoporosis is a metabolic bone disease characterized by decreased bone mineral density (BMD) and increased bone fragility, resulting from the rapid drop of endogenous estrogen level that is experienced by 40% of postmenopausal women (Stein et al, 2014). Postmenopausal bone loss is the result of the reduced ovarian follicular activity and changes in female reproductive hormone levels [a decrease in estrogen and an increase in follicle stimulating hormone (FSH) and/or luteinizing hormone (LH) level] in the circulation of women during menopause (Lindsay, 2004). Hormone replacement therapy (HRT) was used to be the gold standard for management of postmenopausal osteoporosis (de Villiers et al, 2013) as it could significantly decrease the risk of bone fracture in postmenopausal women. With the evidence of the association of HRT use with an increased risk of breast cancer, endometrial cancer, and stroke in postmenopausal women, its clinical use for management of menopausal symptoms has been limited (Davison and Davis, 2003). Extensive efforts from the scientific communities are devoted to develop alternative regimen for management of menopausal symptoms and postmenopausal osteoporosis that is effective and without undesirable side effects
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