Jin Xiang, Wang Hong, Liang Xuechao, Ru Kang, Deng Xiaoni, Gao Shuo, Qiu Wuxia, Huai Ying, Zhang Jiaqi, Lai Linbin, Li Fan, Miao Zhiping, Zhang Wenjuan, Qian Airong
Lab for Bone Metabolism, Xi'an Key Laboratory of Special Medicine and Health Engineering; Key Lab for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, China.
Research Center for Special Medicine and Health Systems Engineering, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, China.
NPJ Microgravity. 2022 Jul 6;8(1):23. doi: 10.1038/s41526-022-00210-x.
Bone loss induced by microgravity exposure seriously endangers the astronauts' health, but its countermeasures still have certain limitations. The study aims to find potential protective drugs for the prevention of the microgravity-induced bone loss. Here, we utilized the network pharmacology approach to discover a natural compound calycosin by constructing the compound-target interaction network and analyzing the topological characteristics of the network. Furthermore, the hind limb unloading (HLU) rats' model was conducted to investigate the potential effects of calycosin in the prevention of bone loss induced by microgravity. The results indicated that calycosin treatment group significantly increased the bone mineral density (BMD), ameliorated the microstructure of femoral trabecular bone, the thickness of cortical bone and the biomechanical properties of the bone in rats, compared that in the HLU group. The analysis of bone turnover markers in serum showed that both the bone formation markers and bone resorption markers decreased after calycosin treatment. Moreover, we found that bone remodeling-related cytokines in serum including IFN-γ, IL-6, IL-8, IL-12, IL-4, IL-10 and TNF-α were partly recovered after calycosin treatment compared with HLU group. In conclusion, calycosin partly recovered hind limb unloading-induced bone loss through the regulation of bone remodeling. These results provided the evidence that calycosin might play an important role in maintaining bone mass in HLU rats, indicating its promising application in the treatment of bone loss induced by microgravity.
微重力暴露引起的骨质流失严重危及宇航员的健康，但其应对措施仍有一定局限性。本研究旨在寻找预防微重力引起的骨质流失的潜在保护药物。在此，我们利用网络药理学方法，通过构建化合物-靶点相互作用网络并分析网络的拓扑特征，发现了一种天然化合物毛蕊异黄酮。此外，通过建立后肢卸载（HLU）大鼠模型，研究毛蕊异黄酮在预防微重力引起的骨质流失方面的潜在作用。结果表明，与HLU组相比，毛蕊异黄酮治疗组大鼠的骨密度（BMD）显著增加，股骨小梁骨的微观结构、皮质骨厚度和骨生物力学性能均得到改善。血清骨转换标志物分析表明，毛蕊异黄酮治疗后骨形成标志物和骨吸收标志物均降低。此外，我们发现，与HLU组相比，毛蕊异黄酮治疗后血清中包括IFN-γ、IL-6、IL-8、IL-12、IL-4、IL-10和TNF-α在内的骨重塑相关细胞因子部分恢复。总之，毛蕊异黄酮通过调节骨重塑部分恢复了后肢卸载引起的骨质流失。这些结果证明毛蕊异黄酮可能在维持HLU大鼠骨量方面发挥重要作用，表明其在治疗微重力引起的骨质流失方面具有广阔的应用前景。
