基于网络药理学探讨桃红四物汤治疗骨质疏松症的主要活性成分及药理作用机制

On the Main Active Components and Pharmacological Mechanism of Taohong Siwu Tang(桃红四物汤)in the Treatment of Osteoporosis Based on Network Pharmacology

目的:从网络药理学角度研究桃红四物汤治疗骨质疏松症的主要活性成分及多维药理作用机制。方法:从中药系统药理学数据库和分析平台中提取桃红四物汤的化学成分,以口服生物利用度(OB)≥30%和类药性(DL)≥0.18筛选活性成分,通过该数据库提取活性成分作用靶点,以GeneCards和OMIM在线分析平台挖掘靶点相关疾病,采用Cytoscape 3.7.2软件构建活性成分−作用靶点网络,String10.0构建蛋白-蛋白相互作用(PPI)网络,最后通过基因本体(GO)和基因组百科全书(KEGG)富集分析桃红四物汤治疗骨质疏松症的药理作用机制。结果:共筛选得到桃红四物汤69个活性成分,涉及5346个作用靶点,主要涉及破骨细胞分化,激素,相关炎症因子,甲状旁腺激素的合成、分泌及作用等生物过程,通过调节白细胞介素-17、辅助性T细胞17、T细胞受体、Toll样受体、雌激素、丝裂原活化蛋白激酶、PI3K-Akt、甲状腺激素、FoxO、Wnt等信号通路发挥治疗骨质疏松症的作用。结论:本研究体现了桃红四物汤多成分−多靶点−多途径的作用特点,为进一步开展桃红四物汤治疗骨质疏松症作用机制的研究提供了新的思路与方法。

Objective:To study the main active components and multi-dimensional pharmacological mechanism of Taohong Siwu Tang(桃红四物汤)in the treatment of osteoporosis from the perspective of network pharmacology.Methods:The chemical components of Taohong Siwu Tang were got from the pharmacology database and analysis platform of traditional Chinese medicine system,and the active components were screened by the standards of OB≥30%and DL≥0.18.The action targets of active components were got from the database,and the target-related diseases were mined by GeneCards and OMIM online analysis platforms.The active components-action target network was constructed by software Cytoscape 3.7.2 and protein-protein interaction(PPI)network was constructed by String 10.0.Finally,GO and KEGG enrichment were used to analyze the pharmacological mechanism of Taohong Siwu Tang in the treatment of osteoporosis.Results:A total of 69 active components of Taohong Siwu Tang were screened,involving 5346 action targets,mainly involving osteoclast differentiation,hormones,related inflammatory factors,synthesis,secretion and role of parathyroid hormone,which play roles in the treatment of osteoporosis through regulating interleukin-17,helper T cell 17,T cell receptor,toll like receptor,estrogen,mitogen activated protein kinase,PI3K-Akt,thyroid hormone,and signaling pathways of FoxO and Wnt.Conclusion:This study reflects the characteristics of multi-component,multitarget and multi-channel action of Taohong Siwu Tang,which provides new ideas and methods for further research on the mechanism of it in the treatment of osteoporosis.