基于逆向网络药理学探讨绝经后骨质疏松病机及中药组方预测

Exploring the pathogenesis of postmenopausal osteoporosis and predicting traditional Chinese medicine prescriptions based on reverse network pharmacology

目的 探讨绝经后骨质疏松的发病机制,并基于逆向网络药理学进行靶点和中药成分的分子对接验证及中药组方预测。方法 利用韦恩图提取并展示“骨质疏松”与“绝经后”的共有靶点;对提取的共有靶点进行基因本体(gene ontology,GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析;构建蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络以明确绝经后骨质疏松的发病机制、通路和关键靶点,最终构建关键靶点-有效成分-中药网络,确定度值较高的中药并整理其性、味、归经。结果 针对绝经后骨质疏松,保留度值≥10的17个可匹配中药成分的关键靶点,于中药系统药理学数据库和分析平台(traditional Chinese medicine systems pharmacology data base and analysis platform,TCMSP)中匹配中药成分信息,以度值最高的3个靶点与度值≥5且口服生物利用度≥30%、类药性≥0.18的6种中药成分进行18次分子对接验证,结果稳定且良好。逆向收集300种中药,其中度值≥4的52种中药以寒性药、苦味药居多;在归经上,以肝、肺经居多;在功效上,以活血化瘀居多。结论 运用逆向网络药理学思维及分子对接技术对绝经后骨质疏松进行靶点、通路、成分和中药预测;结合临床实践,在辨证论治绝经后骨质疏松治疗中适当加入苦寒、归肝肺经、活血化瘀类药物并适当添加银杏叶、菟丝子、鸡血藤、甘草、黄芪等中药以改善关节炎症、抑制破骨细胞分化、促进成骨细胞分化、预防骨质疏松,为今后临床辨证论治中药组方拓宽思路。

Objective To discuss the pathogenesis of postmenopausal osteoporosis,and to validate molecular docking and predict the composition of traditional Chinese medicine based on reverse network pharmacological.Methods The shared targets of?osteoporosis?and損ostmenopausal?l?were extracted and demonstrated by using Venn diagram.The common targets were analyzed for gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment.The protein-protein interaction(PPI)network was constructed to clarify the pathogenesis,pathways and key targets of postmenopausal osteoporosis,and finally the key target-active ingredient-traditional Chinese medicine network was constructed,and the characteristics,taste and tropism of traditional Chinese medicines with high identification values were sorted out.Results For postmenopausal osteoporosis,17 key targets of which degree value≥10 that could match with traditional Chinese medicines were analysis in traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP),and the results of 18 times of molecular docking tests were stable and good which performed on the highest degree value 3 targets with 6 traditional Chinese medicines components(degree value≥5,oral bioavailability≥30%,drug likeness≥0.18).Collected 52 kinds of traditional Chinese medicines(degree value≥4)were mainly cold and bitter,belonging to liver and lung channels in channel tropism,promoting blood circulation and removing blood stasis in efficacy from 300 kinds of traditional Chinese medicines.Conclusion In this study,the targets,pathways,compositions and prescriptions were predicted for postmenopausal osteoporosis based on reverse network pharmacological and molecular docking.However,the thinking be broadening for the formulation of traditional Chinese medicine which appropriately added bitter cold drugs、drugs entering liver and lung channels,blood-activating and blood-stasis removing drugs and high-value Chinese medicines such as Ginkgo biloba,Cuscuta,Cauleratholoba,Licorice and Astragalus to improve joint inflammation,inhibit osteoclast differentiation,promote osteoblast differentiation and prevent osteoporosis for the treatment of postmenopausal osteoporosis.