State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.
J Ethnopharmacol. 2021 May 10;271:113899. doi: 10.1016/j.jep.2021.113899. Epub 2021 Feb 5.
Traditional Chinese medicine Cistanche deserticola Y. C. Ma has effect of "tonifying kidney and strengthening bone". However, the specific active extracts of C. deserticola and mechanisms for treatment of osteoporotic are not clear.
We wanted to identify the effective component extracts of C. deserticola for the treatment of osteoporosis and the potential mechanisms.
Our group researched the extracts of C. deserticola with anti-osteoporotic activity, including total glycosides (TGs), polysaccharides (PSs), and oligosaccharides (OSs) in senescence accelerated mouse prone 6 (SAMP6) mice. The Goldner's Trichrome, Van Gieson's (VG), Safranin O-Fast Green staining and Von Kossa staining were performed to investigate the bone structure formation and calcium deposits. Serum was collected for detecting biochemical markers. Bone micro-architecture was detected by micro-CT. Expressions of bone morphogenetic protein-2 (BMP-2), osteocalcin (OCN), osteoprotegerin (OPG), receptor activator of nuclear factor-κ B ligand (RANKL), p-glycogen synthetase kinase-3β (p-GSK-3β), and p-β-catenin were analyzed by western blotting and immunohistochemistry.
TGs and PSs ameliorated bone histopathological damages, promoted the formation of new bone, collagenous fiber, and chondrocytes, and accelerated the calcium deposits. Moreover, they remarkable altered the biomarkers of bone turnover and effectively ameliorated bone microarchitecture. The further mechanisms study showed that TGs and PSs significantly decreased the expressions of RANKL, p-β-catenin, as well as up-regulated the expression of BMP-2, OCN, OPG, and p-GSK-3β (Ser9).
The findings of this study suggest that TGs and PSs can promote osteoblastogenic bone formation and improve bone microstructure damage in SAMP6 mice, and their therapeutic effect on osteoporosis is via activating Wnt/β-catenin signaling pathway.
传统中药肉苁蓉具有“补肾强骨”的功效。然而，肉苁蓉具体的活性提取物及治疗骨质疏松的机制尚不清楚。
本研究旨在鉴定肉苁蓉治疗骨质疏松的有效成分提取物及其潜在机制。
本研究组研究了具有抗骨质疏松活性的肉苁蓉提取物，包括总糖苷（TGs）、多糖（PSs）和低聚糖（OSs）在快速老化模型小鼠（SAMP6）中的作用。采用 Goldner's Trichrome、Van Gieson（VG）、Safranin O-Fast Green 染色和 Von Kossa 染色观察骨结构形成和钙沉积。收集血清检测生化标志物。采用 micro-CT 检测骨微结构。采用 Western blot 和免疫组化分析骨形态发生蛋白 2（BMP-2）、骨钙素（OCN）、护骨素（OPG）、核因子-κB 受体激活剂配体（RANKL）、糖原合酶激酶 3β（p-GSK-3β）和 p-β-连环蛋白的表达。
TGs 和 PSs 改善了骨组织病理学损伤，促进了新骨、胶原纤维和软骨细胞的形成，加速了钙沉积。此外，它们显著改变了骨转换的生物标志物，有效地改善了骨微结构。进一步的机制研究表明，TGs 和 PSs 显著降低了 RANKL、p-β-连环蛋白的表达，同时上调了 BMP-2、OCN、OPG 和 p-GSK-3β（Ser9）的表达。
本研究结果表明，TGs 和 PSs 可促进成骨细胞形成骨，改善 SAMP6 小鼠骨微结构损伤，其治疗骨质疏松症的作用机制可能是通过激活 Wnt/β-连环蛋白信号通路。
