Ye Qi, Ma Xue-Qin, Hu Chang-Ling, Lin Bing, Xu Li-Sheng, Zheng Cheng-Jian, Qin Lu-Ping
Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai, 200433, China; Department of Biological Science, College of Life Science, Fujian Agriculture and Forestry University, 15 Shangxiadian Road, Fuzhou, 350002, China.
Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai, 200433, China; Department of Pharmaceutical analysis, School of Pharmacy, NingXia Medical University, 1160 Shenli Street, Yinchuan, 750004, China.
Phytomedicine. 2015 Jan 15;22(1):94-102. doi: 10.1016/j.phymed.2014.11.004. Epub 2014 Nov 20.
Our study aimed to investigate the antiosteoporotic properties of the ethanol extract of Podocarpium podocarpum (DC.) Yang et Huang (PE) in ovariectomized (OVX) rats and to characterize the active constituents. As a result, PE significantly inhibited the increased urinary Ca excretion and activity of bone resorption markers including tartrate-resistant acid phosphatase (TRAP), deoxypyridinoline crosslinks and cathepsin K in OVX rats, whereas exhibited little effects on the body, uterus and vagina weight. Detailed micro-CT analysis showed that PE notably enhanced bone quality, with increased bone mineral content (BMC), bone volume fraction (BVF), connectivity density (CD), tissue mineral content (TMC), tissue mineral density (TMD) and trabecular number (Tb. N), and decreased trabecular separation (Tb. Sp), in OVX animal. Those findings implied that PE had notable antiosteoporotic effect, especially effective in preventing bone resorption, with little side-effects on reproductive tissue. Further chemical investigation led to the isolation of 17 flavonoids, most of which showed significantly stimulatory effect on osteoblastic proliferation, ALP activity and mineralized nodes formation as well as inhibitory effect on osteoclastic TRAP activity in osteoblastic and osteoclastic cells. Our results indicated that PE, with abundant flavonoids, had remarkable antiosteoporotic activity and therefore can be a promising candidate for the treatment of postmenopausal osteoporosis induced by estrogen deficiency through herbal remedy.
我们的研究旨在探讨长柄山蚂蝗(Podocarpium podocarpum (DC.) Yang et Huang)乙醇提取物(PE)对去卵巢(OVX)大鼠的抗骨质疏松特性,并鉴定其活性成分。结果显示,PE显著抑制了OVX大鼠尿钙排泄的增加以及骨吸收标志物的活性,这些标志物包括抗酒石酸酸性磷酸酶(TRAP)、脱氧吡啶啉交联物和组织蛋白酶K,而对大鼠的体重、子宫和阴道重量影响甚微。详细的显微CT分析表明,PE显著改善了OVX动物的骨质量,增加了骨矿物质含量(BMC)、骨体积分数(BVF)、连通性密度(CD)、组织矿物质含量(TMC)、组织矿物质密度(TMD)和骨小梁数量(Tb.N),并减小了骨小梁间距(Tb.Sp)。这些发现表明,PE具有显著的抗骨质疏松作用,尤其在预防骨吸收方面效果显著,且对生殖组织几乎没有副作用。进一步的化学研究分离出了17种黄酮类化合物,其中大多数对成骨细胞增殖、碱性磷酸酶(ALP)活性和矿化结节形成具有显著的促进作用,对成骨细胞和破骨细胞中的破骨细胞TRAP活性具有抑制作用。我们的结果表明,富含黄酮类化合物的PE具有显著的抗骨质疏松活性,因此有望成为通过草药疗法治疗雌激素缺乏引起的绝经后骨质疏松症的候选药物。