基于网络药理学和分子对接探讨中药丹参治疗股骨头坏死的作用机制

Action mechanism of Salvia miltiorrhiza in femoral head necrosis based on network pharmacology and molecular docking

摘要:

目的 利用网络药理学和分子对接探讨中药丹参治疗股骨头坏死（ONFH）的作用机制。方法 通过中药 系统药理学数据库和分析平台TCMSP筛选丹参有效活性成分及作用靶点，OMIM、GeneCards、NCBI和DisGeNET数据 库收集ONFH疾病靶点。利用jevnn获取丹参与ONFH交集靶点，并进行GO和KEGG富集分析，利用Cytoscape软件绘出 “成分-靶点-疾病”的网络图，最后对药物核心成分与交集靶点进行分子对接验证。结果 筛选出丹参与ONFH的交集 靶点有 74 个，包括EZH2、CYP19A1、EGFR、PTPN6、OPRM1 等。丹参抗ONFH核心成分有 19 个，包括木犀草素、紫丹 参素C、异丹参酮II、丹参酮IIA等；存在潜在调控通路共 237 个，主要为AGE/RAGE、流体剪切应力、动脉粥样硬化、TNF 等信号通路。分子对接显示丹参酮IIA、木犀草素与EZH2 之间有结合活性，丹参酮IIA、木犀草素与EGFR之间有强烈的 结合活性。结论 丹参可以通过多个成分、多个靶点途径发挥治疗ONFH的作用，主要与促血管内皮增殖、影响骨细胞分 化及调节血流动力学等机制有关。

Abstract:

Abstract: Objective To explore the action mechanism of Salvia miltiorrhiza (Sm) in osteonecrosis of femoral head (ONFH) using network pharmacology and molecular docking. Methods The active components and targets of Sm were screened by TCMSP, while disease targets of ONFH were collected by OMIM, GeneCards, NCBI and DisGeNET databases. The intersection targets between Sm and ONFH were analyzed by Jevnn, GO and KEGG. The network diagram of “component-target-disease” was drawn by Cytoscape software, and the core components and intersection targets were verified by molecular docking. Results Seventy-four intersecting targets between Sm and ONFH were screened, mainly including EZH2, CYP19A1, EGFR, PTPN6 and OPRM1. There were 19 core components of Sm against ONFH, such as luteolin, salvianolic acid C, isotanshinone II, tanshinone IIA, etc. of 237 potential regulatory pathways, AGE/RAGE, fluid shear stress, atherosclerosis, and TNF were most common. Molecular docking showed that tanshinone IIA and luteolin had potential binding activities with EZH2 and EGFR. Conclusion Sm can play a role in ONFH through multiple components and targets, which may be mainly related to vascular endothelial proliferation, osteocyte differentiation and hemodynamics.