Ma H-P, Ma X-N, Ge B-F, Zhen P, Zhou J, Gao Y-H, Xian C J, Chen K-M
Department of Pharmacy, Lanzhou General Hospital, Lanzhou Command of CPLA, Lanzhou, 730050, China.
Cell Prolif. 2014 Dec;47(6):527-39. doi: 10.1111/cpr.12147. Epub 2014 Oct 30.
Icariin, a prenylated flavonol glycoside isolated from traditional Chinese medicinal herb of the genus Epimedium, has been demonstrated to be a potential alternative therapy for osteoporosis, and its action mechanism so far has been mainly attributed to its phytoestrogenic property. As blood supply to bone is considerably reduced with ageing and by the menopause, we hypothesized that icariin treatment would reduce bone loss by preventing ischaemia-induced hypoxic damages to bone.
To investigate effects of icariin treatment on cultured rat calvarial osteoblasts exposed to hypoxic conditions (2% oxygen).
Compared to normoxic control, cell viability decreased with time to 50% by 48 h in the hypoxic group, and icariin attenuated the reduction, dose dependently, with 10(-6) and 10(-5) m concentrations showing significant protective effects. Icariin also inhibited increase of lactate dehydrogenase activity in culture media. Measurements on oxidative stress, cell cycling and cell survival indicated that icariin protected osteoblasts by reducing production of reactive oxygen species and malondialdehyde, increasing superoxide dismutase activity, arresting the cell cycle and inhibiting apoptosis. Icariin also preserved osteogenic differentiation potential of the hypoxic cells in a dose-dependent manner, compared to the hypoxia alone group, as revealed by increased levels of RUNX-2, OSX and BMP-2 gene expression, alkaline phosphatase activity, and formation of mineralized nodules.
Our results demonstrated that icariin attenuated oxidative stress and apoptosis and preserved viability and osteogenic potential of osteoblasts exposed to hypoxia in vitro, and suggested that its anti-osteoporotic effect may be attributed to its anti-hypoxic activity and phytoestrogenic properties.
淫羊藿苷是从淫羊藿属传统中药材中分离得到的一种异戊烯基黄酮醇苷，已被证明是骨质疏松症的一种潜在替代疗法，其作用机制目前主要归因于其植物雌激素特性。随着年龄增长和绝经，骨骼的血液供应会显著减少，因此我们推测淫羊藿苷治疗可通过预防缺血诱导的骨缺氧损伤来减少骨质流失。
研究淫羊藿苷处理对暴露于低氧条件（2%氧气）下的培养大鼠颅骨成骨细胞的影响。
与常氧对照组相比，低氧组细胞活力随时间下降，至48小时时降至50%，而淫羊藿苷可剂量依赖性地减轻这种下降，10(-6)和10(-5) m浓度显示出显著的保护作用。淫羊藿苷还抑制了培养基中乳酸脱氢酶活性的增加。对氧化应激、细胞周期和细胞存活的测量表明，淫羊藿苷通过减少活性氧和丙二醛的产生、增加超氧化物歧化酶活性、使细胞周期停滞和抑制凋亡来保护成骨细胞。与单独低氧组相比，淫羊藿苷还以剂量依赖性方式保留了低氧细胞的成骨分化潜能，这通过RUNX-2、OSX和BMP-2基因表达水平的升高、碱性磷酸酶活性以及矿化结节的形成得以体现。
我们的结果表明，淫羊藿苷在体外减轻了氧化应激和凋亡，保留了暴露于低氧环境下的成骨细胞的活力和成骨潜能，并提示其抗骨质疏松作用可能归因于其抗缺氧活性和植物雌激素特性。
