中国骨质疏松杂志

基于网络药理学探讨青娥丸治疗绝经后骨质疏松症的作用机制

Investigation of the mechanism of the effect of Qinge pill on postmenopausal osteoporosis based on network pharmacology

DOI：10.3969/j.issn.1006-7108.2021.03.011

中文关键词: 绝经后骨质疏松症青娥丸网络药理学信号通路

英文关键词:postmenopausal osteoporosis Qinge pill network pharmacology signaling pathway

基金项目:国家自然科学基金项目（81603638）；中国博士后科学基金面上项目（2019M662791）；北京中医药大学2019年度基础科研业务费项目（2019-JYB-JS-042）；北京中医药大学东直门医院青苗人才项目（DZMY-201702）

作者	单位
邸学士1 陈昭2 贾育松2 李晋玉2 郑晨颖2 白春晓2 张帆2 刘楚吟2 袁巧妹1 龙水文1 冉宇1 康晟乾1 陈江2*	1.北京中医药大学，北京 100029 2.北京中医药大学东直门医院，北京 100700

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中文摘要:

目的运用网络药理学的方法探讨青娥丸治疗PMO可能的分子作用机制。方法运用TCMSP、ETCM、SymMap数据库及文献挖掘获取青娥丸主要活性成分，通过SwissTargetPrediction平台进行成分靶标预测；经GeneCards、OMIM和DisGeNET数据库获取PMO相关靶点，与成分靶点取交集，获得青娥丸治疗PMO的潜在作用靶点；应用Cytoscape软件构建青娥丸治疗PMO的中药-活性成分-交集靶点网络图，使用String数据库及Cytoscape软件对交集靶点进行蛋白质相互作用网络分析，依据节点度值筛选关键靶点；通过DAVID平台对关键靶点进行GO和KEGG富集分析，以探究青娥丸治疗PMO的分子作用机制。结果筛选出青娥丸活性成分40个，包括飞燕草素、槲皮素、山奈酚等核心成分；青娥丸治疗PMO的潜在作用靶点178个；对交集靶点进行蛋白质互相作用网络分析获取关键靶点68个，包括MAPK1、AKT1、PIK3CA、JAK2等核心靶点；关键靶点基因的GO及KEGG富集分析显示：关键靶标主要在质膜、膜筏、细胞核等位置发挥作用，通过一氧化氮生物合成过程的正调控、信号转导、蛋白质磷酸化等生物过程，发挥激酶活性、与蛋白质结合、与蛋白激酶结合等功能。关键靶点主要通过参与癌症通路、PI3K-Akt信号通路、HIF-1信号通路、以及雌激素、催乳素、甲状腺素类信号通路对PMO进行调控。结论青娥丸中飞燕草素、槲皮素、山奈酚等核心成分，可能通过参与PI3K-Akt、HIF-1、雌激素、催乳素等信号通路，作用于MAPK1、AKT1、PIK3CA、JAK2等基因靶点，调节骨代谢，治疗PMO。

英文摘要:

Objective To integrate the mechanism of Qinge pill in the treatment of postmenopausal osteoporosis (PMO) with network pharmacology approach. Methods The main active components of Qinge pill were obtained by using TCMSP, ETCM, and SymMap database and Literature retrieval. The component target prediction was performed using Swiss Target Prediction. PMO-related targets were obtained through the GeneCards database, OMIM database, and DisGeNET database, and the intersections with the drug targets was caught to obtain the potential therapeutic targets of Qinge pill for PMO. Cytoscape software was used to construct the network diagram of TCM, active ingredient, and intersection target of Qinge pill for PMO treatment. The protein–protein interaction network was analyzed using the String database and Cytoscape software. The key targets were selected according to the degree value. The gene ontology function and KEGG pathway enrichment analysis were performed on the key targets using DAVID database to explore the mechanism of Qinge pill in the treatment of PMO. Results 40 active ingredients were selected, including delphinidin, quercetin, and kaempferol, etc. 178 potential targets of Qinge pill in the treatment of PMO were found. By analyzing the protein interaction network of intersection targets, 68 key targets were obtained, mainly including MAPK1, AKT1, PIK3CA, and JAK2, etc. The GO and KEGG enrichment analysis of key target genes showed that the key targets mainly played roles in plasma membrane, membrane raft, nucleus, and other positions, and carried out the positive regulation of nitric oxide biosynthesis, signal transduction, protein phosphorylation, and other biological processes. and functioned in kinase activity, protein binding, and protein kinases binding. Moreover, the key targets regulated PMO through cancer pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, and estrogen, prolactin, and thyroid hormone signaling pathways. Conclusion The active components in Qinge pills, such as delphinidin, quercetin, and kaempferol, may regulate bone metabolism and treat PMO by participating in PI3K-Akt, HIF-1, estrogen and prolactin signaling pathways and acting on MAPK1, AKT1, PIK3CA, and JAK2 gene targets.

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