桃红四物汤治疗骨质疏松性骨折的网络药理学和分子对接研究
Study on the mechanism of Taohong Siwu decoction in the treatment of osteoporotic fractures based on network pharmacology and molecular docking
  
DOI:10.3969/j.issn.1006-7108.2022.05.013
中文关键词:  骨质疏松性骨折  网络药理学  桃红四物汤  分子对接  作用机制
英文关键词:osteoporotic fracture  network pharmacology  Taohong Siwu decoction  molecular docking  functional mechanism
基金项目:中央级公益性科研院所基本科研业务费自主选题(ZZ11-034)
作者单位
白万辉1 赵勇2* 王旋2 陈泓颖1 韦俊余2 秦伟凯2 1.北京中医药大学北京 100029 2.中国中医科学院望京医院北京 100102 
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中文摘要:
      目的 运用网络药理学和分子对接的技术,研究桃红四物汤作用于骨质疏松性骨折的潜在作用机制。方法 检索TCMSP,获取桃红四物汤药物的有效成分、潜在靶点,运用GeneCards、OMIM、DrugBank、DisGeNET数据库收集骨质疏松性骨折的相关靶点,获取药物和疾病的交集靶点,并通过Cytoscape 3.8.2软件构建“药物-成分-靶点-疾病”可视化网络图,筛选出药物关键成分。将交集靶点上传到STRING数据库,并绘制PPI网络图,筛选核心靶点;并使用Metascape数据库进行交集靶点的GO以及KEGG通路的富集分析。最后运用 AutoDock Tools1.5.6和Pymol2.4.1软件,分子对接关键成分与核心靶点。结果 桃红四物汤与骨质疏松性骨折的交集靶点有152个,“药物-成分-靶点-疾病”网络图及PPI提示IL6、JUN、AKT1、MAPK1、TNF可能是桃红四物汤治疗骨质疏松性骨折的关键靶点。GO富集分析显示,桃红四物汤治疗骨质疏松性骨折的交集靶点的生物功能主要涉及炎症免疫、细胞增殖分化、细胞凋亡等方面。KEGG通路富集分析显示,桃红四物汤治疗骨质疏松性骨折的交集靶点主要涉及IL17、PI3K-Akt、HIF-1、甲状腺激素等信号通路。结论 桃红四物汤从多靶点、多成分及多通路作用于骨质疏松性骨折,主要起到调控骨细胞增殖分化、细胞凋亡、抗炎免疫等作用,今后从生物实验方面进一步深入揭示其作用机制具有研究意义。
英文摘要:
      Objective To investigate the potential mechanism of action of Taohong Siwu decoction in the treatment of osteoporotic fractures by using network pharmacology and molecular docking. Methods The active ingredients and potential targets of Taohong Siwu decoction were screened through TCMSP. GeneCards, OMIM, DrugBank, and DisGeNET databases were used to collect the relevant targets of osteoporotic fractures. A drug-component-target-disease visual network diagram was constructed using Cytoscape 3.8.2 software to screen out the key components of the drug. The intersecting targets were uploaded to the STRING database and the PPI network map was drawn to screen the core targets. The Metascape database was used to perform GO and KEGG pathway enrichment analysis of the intersecting targets. Finally, AutoDock Tools 1.5.6 and Pymol 2.4.1 software were used to molecularly dock the key components to the core targets. Results There were 152 intersecting targets between Taohong Siwu decoction and osteoporotic fractures. Drug-component-target-disease diagram and PPI results suggested that IL6, JUN, AKT1, MAPK1, TNF might be the core targets of the drug. The GO enrichment analysis showed that the biological functions of the intersecting targets were mainly related to inflammatory immunity, cell proliferation and differentiation, and apoptosis, etc. The KEGG pathway enrichment analysis showed that the network of intersecting targets for Taohong Siwu decoction for osteoporotic fractures mainly included IL17, PI3K-Akt, HIF-1, and Hyroid hormone signaling pathways. Conclusion Taohong Siwu decoction acts on osteoporotic fractures through multiple targets, components, and pathways, and mainly on the regulation of proliferation and differentiation of bone cells, anti-inflammatory, immunity, estrogen synthesis. Further study in biological experiments is meaningful for its’ functional mechanism in the future.
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