Antiosteoporotic effect of icariin in ovariectomized rats is mediated via the Wnt/β-catenin pathway.
Antiosteoporotic effect of icariin in ovariectomized rats is mediated via the Wnt/β-catenin pathway.
复制标题
DOI：
10.3892/etm.2016.3333
复制
发表时间：
2016-07
影响因子：
2.7
通讯作者：
Zhang R
中科院分区：
文献类型：
--
作者：
Chen G;Wang C;Wang J;Yin S;Gao H;Xiang LU;Liu H;Xiong Y;Wang P;Zhu X;Yang LI;Zhang R
淫羊藿苷（伊卡）是从淫羊藿中分离的主要活性黄酮苷，体外实验显示其具有预防绝经后骨质丢失的作用。然而，伊卡防止体内骨丢失的机制仍然知之甚少。在本研究中，伊卡在卵巢切除（OVX）大鼠骨质疏松症模型中的作用进行了评价。SD大鼠分为假手术组和去卵巢组。将OVX大鼠随机分为5组：OVX组（仅饮水）、福善美（阳性）组（5.04 mg/kg，每周一次，口服）和OVX-ICA组（125、250和500 mg/kg，每日一次，口服），治疗12周。将125、250和500 mg/kg伊卡剂量分别指定为低（L-ICA）、中（M-ICA）和高（H-ICA）。与假手术组相比，OVX组大鼠骨密度（BMD）明显降低，血清骨保护素（OPG）含量明显降低，血清骨钙素（BGP）含量明显升高。伊卡显著增加BMD、生物力学强度、骨小梁数量和骨小梁厚度，减少腰椎骨小梁分离。伊卡治疗还通过增加血清OPG和BGP浓度使成骨细胞标志物的表达完全正常化。通过分化标志物表达的增加证明了矿化的增强。虽然需要进一步的体内研究来研究伊卡在改善骨量方面的功效，但本研究表明伊卡具有强成骨活性，诱导成骨分化并抑制破骨细胞的再吸收。根据BMD、生化标志物、生物力学试验和组织病理学参数，还证明伊卡具有抗骨质疏松作用。与L-ICA和H-ICA相比，M-ICA更有效，且不引起肝或肾损害。
Icariin (ICA), the main active flavonoid glucoside isolated from Herba Epimedii, has been shown to prevent postmenopausal bone loss in vitro. However, the mechanisms by which ICA prevents bone loss in vivo remain poorly understood. In the present study, the effect of ICA in an ovariectomized (OVX) rat model of osteoporosis was evaluated. Sprague-Dawley rats were divided into sham-operated and OVX groups. The OVX rats were randomly divided into five groups: OVX group (water only), Fosamax (positive) group (5.04 mg/kg, weekly, administered orally), and OVX-ICA groups (125, 250 or 500 mg/kg, daily, administered orally) and treated for 12 weeks. The 125, 250 and 500 mg/kg doses of ICA were designated as low (L-ICA), medium (M-ICA) and high (H-ICA), respectively. Compared with the sham-operated group, the OVX rats had significantly decreased bone mineral density (BMD), reduced serum osteoprotegerin (OPG) and increased serum bone gla protein (BGP) concentrations. ICA significantly increased BMD, biomechanical strength, trabecular bone number and trabecular bone thickness, and reduced lumbar trabecular bone separation. Treatment with ICA also completely normalized the expression of osteoblast markers by increasing serum concentrations of OPG and BGP. Enhanced mineralization was demonstrated by increased expression of differentiation markers. Although further in vivo studies are required to investigate the efficacy of ICA in improving bone mass, this study demonstrates that ICA has strong osteogenic activity, inducing osteogenic differentiation and inhibiting resorption by osteoclasts. It also demonstrates an antiosteoporotic effect for ICA on the basis of BMD, biochemical markers, biomechanical tests and histopathological parameters. Compared with L-ICA and H-ICA, M-ICA was more effective and caused no liver or kidney damage.