基于网络药理学和分子对接探讨刺老苞防治骨质疏松症的作用机制

孙雅嘉; 孙九许; 侯思瀚; 燕梦云; 裴凌鹏

doi:10.13386/j.issn1002-0306.2021100014

基于网络药理学和分子对接探讨刺老苞防治骨质疏松症的作用机制

Mechanism of Aralia echinocaulis in Treatment of Osteoporosis Based on Network Pharmacology and Molecular Docking

摘要

摘要: 目的：基于网络药理学和分子对接探讨刺老苞防治骨质疏松症的作用机制。方法：通过色谱-质谱联用得到刺老苞药材的化学成分信息，然后利用Stitch数据库预测其作用的靶点。应用GeneCards等数据库获取与骨质疏松症相关的疾病靶点。通过去异存同得出两者之间的交集靶点，对交集靶点进行基因本体注释（GO）及通路富集分析（KEGG），分子对接对预测出的核心靶点与关联化合物进行验证。结果：经色谱-质谱联用分析和数据库预测，获得159个活性成分及525个作用靶点，与1636个骨质疏松症相关靶点取交集得到150个交集靶点。通过PPI网络筛选出IL6、AKT1、MAPK1等10个关键靶点。GO分析显示生物功能578个，涉及基因调控、细胞增殖与凋亡、炎症反应等。KEGG分析显示通路127条，PI3K-Akt信号通路、MAPK信号通路、HIF-1信号通路等可能为关键通路，乙肝、肺结核、类风湿关节炎、癌症等疾病也可能间接导致骨质疏松症。分子对接表明多数成分与关联靶点具有较好的对接能力，说明预测结果具有一定的可靠性。结论：刺老苞多种有效成分可通过促进成骨细胞的存活、增殖与分化，抑制破骨细胞的骨吸收，发挥对骨质疏松症的防治作用，PI3K-Akt信号通路、MAPK信号通路以及HIF-1信号通路在此过程中可能发挥重要作用，为今后分子机制的深入研究以及相应膳食补充剂的开发提供了参考。

Abstract: Objective: Mechanism of Aralia echinocaulis in treatment of osteoporosis based on network pharmacology and molecular docking was discussed. Methods: The chemical components of the Aralia echinocaulis by liquid-phase mass spectrometry were analyzed, Stitch was used to predict the biological macromolecules related to the composition, and the existing targets were collected on DrugBank. GeneCards and other databases were used to obtain targets related to osteoporosis, and the intersection targets between the two were screened out. Gene ontology (GO) enrichment and Genes and Genomes (KEGG) analysis were performed on the intersection targets, and molecular docking was used to verify the predicted core targets and related compounds. Results: After liquid-phase mass spectrometry analysis and database prediction, 159 active ingredients and 525 target points were obtained, and 150 target points were obtained by intersecting with 1636 osteoporosis-related targets. 10 key targets including IL6, AKT1 and MAPK1 were screened out through the protein-protein interaction (PPI) network. GO analysis revealed 578 biological functions, involving gene regulation, cell proliferation and apoptosis, inflammation and so on. KEGG analysis showed 127 pathways, PI3K-Akt signaling pathway, MAPK signaling pathway, and HIF-1 signaling pathway might be key pathways. Diseases such as hepatitis B, tuberculosis, rheumatoid arthritis, and cancer might also indirectly lead to osteoporosis. Molecular docking showed that most components have good docking ability with related targets, indicating that the prediction results have a certain degree of reliability. Conclusion: Multiple effective components of Aralia echinocaulis could prevent and treat osteoporosis by promoting the survival, proliferation and differentiation of osteoblasts and inhibiting bone resorption of osteoclasts. The PI3K-Akt signaling pathway, MAPK signaling pathway and HIF-1 signaling pathway might play an important role in this process, which would provide a reference for the further study of its molecular mechanism and the development of corresponding dietary supplements.