探讨彝药恒古骨伤愈合剂治疗骨质疏松症的系统药理学作用机制

目的 借助系统药理学探讨彝药恒古骨伤愈合剂（osteoking,OK）治疗骨质疏松症（osteoporosis,OP）的药效成分、作用靶点及作用机制，并运用分子对接技术进行对接验证。方法 借助TCMSP筛选OK的活性成分及作用靶点；查询GeneCard、OMIM、DisGeNet、TTD等数据库，筛选OP相关的基因靶点；利用STRING和 Cytoscape 软件构建交集基因靶点蛋白互作网络（PPI），查找OK治疗OP的核心靶点基因，对核心靶点借助DAVID、KEGG Mapper数据库进行GO、KEGG分析。最后运用Autodock进行对接验证。结果 收集到槲皮素、山奈酚、反式十八烷酸、反11-二十碳烯酸、熊果酸、β-谷甾醇、委陵菜酸等主要活性成分；涉及到细胞对脂质、有毒物质、脂多糖、细菌源分子、无机物、有机环化合物、有机氮化合物的反应等生物学过程；可能通过PI3K/Akt、Ras、MAPK等多通路发挥作用。分子对接提示熊果酸与AKT1、ALB、IL-6结合效果较好。结论 初步明确了OK通过多靶点、多通路参与促成骨、抑制破骨的作用，为下一步实验研究提供理论支持与设计思路。

Research on the mechanism of Osteoking treatment of osteoporosis based on systematic pharmacology

Objective To explore the active ingredients, targets and mechanisms of Osteoking(OK, Herbs of the Yi Minority in Yunnan Province) in the treatment of osteoporosis (OP) with the help of systematic pharmacology. And the molecular docking technology is used for docking verification. Methods Screened the active components and targets of OK through TCMSP. Queried GeneCard, OMIM, DisGeNet, TTD Databases to Screening of OP-related gene targets. Constructed the intersection gene target protein-protein interaction(PPI) network by using STRING and Cytoscape Software.The core targets were analyzed by GO and KEGG with the help of DAVID and KEGG Mapper database.Finally, Autodock was used for docking verification. Results The main active components such as quercetin, kaempferoland,11-octadecenoic acid,11-eicosenoic acid,ursolic acid,beta-sitosterol,tormentic acid were collected. It involves biological processes such as cell responses to lipids, toxic substances, lipopolysaccharides, bacterial molecules, inorganic substances, organic ring compounds, organic nitrogen compounds and so on.Theymight play rolesthrough PI3K-Akt, Ras, MAPK, ect multiple pathways.Molecular docking suggested that ursolic acid had better binding effect with AKT1, ALB and IL-6.Conclusion It is preliminarily clear that OK participates in promoting bone formation and inhibiting bone fracture through multi-targets and multi-pathways, which provides theoretical support and design ideas for further experimental research.