Abstract
This study aimed to investigate the osteoprotective effect and the possible molecular mechanisms of the combined extracts of Herba Epimedii and Fructus Ligustri Lucidi on postmenopausal osteoporosis (PMOP). Forty-eight female SD rats were sham-operated (Sham, n = 8) or ovariectomized (OVX, n = 40). Then after a week, OVX rats were divided randomly into five groups (n = 8 in each group): OVX, extracts of Herba Epimedii (HE, 0.35 g/kg), extracts of Fructus Ligustri Lucidi (FLL, 0.35 g/kg), combined extracts of HE and FLL (HE & FLL, 0.20 g/kg HE plus 0.15 g/kg FLL), and Raloxifene hydrochloride (RH, 6.25 mg/kg) groups. All groups were administered once daily for 12 weeks. Indicators related to bone remodeling were detected, including estradiol (E2), bone mineral density (BMD), maximal load, ultimate deflection, micro-CT properties, tartrate-resistant acid phosphatase (TRACP) and alkaline phosphatase (ALP) levels in serum and bone, and the protein and mRNA expression of bone turnover markers (RANKL, M-CSF, Wnt5a, Atp6v0d2, OPG, IGF-1, TGF-β1, and Bmp-2). Results showed that the combined extracts could increase serum E2 levels and BMD, enhance bone strength, reserve bone microstructure degeneration, promote bone formation, and inhibit bone resorption through upregulating the mRNA and protein expression of OPG, IGF-1, TGF-β1, and Bmp-2, while downregulating RANKL, M-CSF, Wnt5a, and Atp6v0d2. These findings demonstrated that the combined extracts of Herba Epimedii and Fructus Ligustri Lucidi with bone protective effects on OVX rats might be an alternative medicine for the treatment of PMOP.
Highlights
Postmenopausal osteoporosis (PMOP) is a serious health problem related to postmenopausal women, which is characterized by skeletal fragility and microarchitecture deterioration [1]
We previously demonstrated that the combined extracts of Herba Epimedii (HE) and Fructus Ligustri Lucidi (FLL) had an osteoprotective effect in osteoporosis rat models induced by retinoic acid and glucocorticoid [4,5,6]
We used dual-energy X-ray absorptiometry (DEXA) to detect the bone mineral density (BMD) levels of right femur to determine whether the extracts have antiPMOP effects
Summary
Postmenopausal osteoporosis (PMOP) is a serious health problem related to postmenopausal women, which is characterized by skeletal fragility and microarchitecture deterioration [1]. The clinical management of PMOP relies on calcium supplement and hormone replacement therapy (HRT), including calcitonin, estrogen, and selective estrogen receptor modulator. Their side-effects, such as gastrointestinal side effects, coronary heart disease, and high risk of gynecological cancer, severely limit their long-term clinical application [2, 3]. According to the theory of TCM that the kidney being in charge of bone is responsible for bone growth and development, Herba Epimedii (HE) and Fructus Ligustri Lucidi (FLL), approved as tonifying-kidney agents by TCM doctor more than 2000 years ago, are often used to treat orthopedic related diseases. The effects of the combined herbs on PMOP were still unclear
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