Li J X, Liu J, He C C, Yu Z Y, Du Y, Kadota S, Seto H
Key Lab of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, PR China.
Maturitas. 2007 Sep 20;58(1):59-69. doi: 10.1016/j.maturitas.2007.06.001. Epub 2007 Jul 20.
Increasing research suggested that Cimicifugae rhizoma might be protective against osteoporosis. In this study, we investigated the effects of three cycloartane-type triterpenoids isolated from Cimicifugae rhizoma, cimicidol-3-O-beta-D-xyloside (1), cimicidanol-3-O-beta-D-xyloside (2) and acetylacteol-3-O-beta-d-xyloside (3) on bone resorption in vitro and bone loss in ovariectomized (OVX) mice.
The activities of the tested compounds on bone resorption were evaluated using three assays, neonatal mouse parietal bone organ culture, osteoclast-like cells (OCLs) formation and pit formation. The effects on bone mineral density (BMD) and uterine weight were examined using OVX mice. Using LC-MS/MS method, the serum concentrations of the triterpenoids were measured in mice serum collected at 0.5, 1, 3, 6 and 12h following its oral administration.
All of the tested compounds exerted the inhibitory effects on bone resorption in bone organ culture, suppressed both of the formation and the resorbing activity of OCLs. Furthermore, a synergistic effect was observed among those compounds. In vivo studies revealed that compounds 1-3 and the mixture of compounds 1-3 prevented the bone loss in OVX mice without affecting uterine weight, and each compound was detected in the mice serum after single oral administration.
The triterpenoids exerted the inhibitory effects on osteoclastic bone resorption through the suppression of both OCLs formation and the resorbing activity of OCLs, and also showed a significant protective effect on BMD in OVX mice. The present results might provide a new pharmacological potential for the treatment of osteoporosis.
越来越多的研究表明，升麻可能对骨质疏松具有保护作用。在本研究中，我们研究了从升麻中分离出的三种环阿尔廷型三萜类化合物，升麻醇 - 3 - O - β - D - 木糖苷（1）、升麻二醇 - 3 - O - β - D - 木糖苷（2）和乙酰升麻醇 - 3 - O - β - D - 木糖苷（3）对体外骨吸收及去卵巢（OVX）小鼠骨质流失的影响。
使用三种实验评估受试化合物对骨吸收的活性，即新生小鼠顶骨器官培养、破骨细胞样细胞（OCLs）形成及骨陷窝形成实验。利用OVX小鼠检测其对骨密度（BMD）和子宫重量的影响。采用液相色谱 - 串联质谱（LC - MS/MS）法，测定口服给药后0.5、1、3、6和12小时采集的小鼠血清中三萜类化合物的浓度。
所有受试化合物在骨器官培养中均对骨吸收发挥抑制作用，抑制了OCLs的形成及其吸收活性。此外，这些化合物之间观察到协同作用。体内研究表明，化合物1 - 3以及化合物1 - 3的混合物可预防OVX小鼠的骨质流失，且不影响子宫重量，单次口服给药后在小鼠血清中均可检测到每种化合物。
三萜类化合物通过抑制OCLs形成及其吸收活性对破骨细胞性骨吸收发挥抑制作用，并对OVX小鼠的骨密度显示出显著的保护作用。本研究结果可能为骨质疏松症的治疗提供新的药理潜力。
