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基于网络药理学探讨牛膝治疗骨质疏松的潜在有效成分及作用机制(1)
http://www.100md.com 2019年11月15日 《中国药房》 201922
     中图分类号 R285 文献标志码 A 文章编号 1001-0408(2019)22-3090-06

    DOI 10.6039/j.issn.1001-0408.2019.22.13

    摘 要 目的:探讨牛膝治疗骨质疏松(OP)的潜在有效成分及作用机制。方法:利用中药系统药理学分析平台数据库(TCMSP)筛选牛膝的有效成分,并收集其对应的作用靶点;使用疾病基因综合数据库(DisGeNET)检索与OP相关的靶点;使用TBtools 1.0绘图软件绘制韦恩图,筛选牛膝有效成分与疾病OP的交集靶点;采用Cytoscape 3.6.1软件和STRING数据库进行“药物-成分-疾病-靶点”网络和蛋白质相互作用(PPI)网络的构建与分析,通过DAVID生物信息学资源数据库进行KEGG通路富集分析。结果:共筛选出牛膝有效成分19个,有效成分与疾病OP的交集靶点有32个。“药物-成分-疾病-靶点”网络中,含节点45个[牛膝、OP节点各1个,有效成分11个(19个有效成分中有8个无对应的OP靶点),交集靶点32个]、边119条,其中槲皮素、山柰酚、汉黄岑素、黄芩苷、大黄藤素等为该网络中较为重要的有效成分。PPI网络中,含节点31个(32个交集靶点中有1个与其余蛋白不关联)、边212条,其中白细胞介素6(IL6)、雌激素受體1、丝裂原活化蛋白激酶1(MAPK1)、IL8、MAPK14等为该网络中的核心靶点。KEGG富集通路共67条,涉及类风湿性关节炎、乙型肝炎、Toll样受体信号通路、磷脂酰肌醇3激酶/蛋白激酶B信号通路、Janus激酶/信号传导及转录激活因子信号通路、核因子κB信号通路等。结论:牛膝中治疗OP的潜在有效成分主要包括槲皮素、山柰酚、汉黄岑素、黄芩苷等,其作用机制可能与参与细胞分化和凋亡、代谢、炎症反应等途径有关,具有多成分、多靶点、多系统的特点。

    关键词 牛膝;骨质疏松;网络药理学;有效成分;作用机制

    Study on Potential Effective Components and Mechanism of Achyranthes bidentata in the Treatment of Osteoporosis Based on Network Pharmacology

    ZHAO Jie1,XU Bo1,LIU Jinbao1,LIANG Xuezhen1,ZHANG Kaibo1,CHEN Shuai2,LIU Yuqing1,LI Gang1(1. First Clinical Medical College, Shandong University of TCM, Jinan 250014, China; 2. College of TCM, Shandong University of TCM, Jinan 250014, China)

    ABSTRACT OBJECTIVE: To investigate the potential effective components and mechanism of Achyranthes bidentata in the treatment of osteoporosis (OP). METHODS: The effective components of A. bidentata were retrieved from the TCMSP database, and corresponding targets of them were collected. The targets related to OP were retrieved from DisGeNET database. TBtools 1.0 mapping software was used to draw the Wayne diagram, and screen the intersecting targets of effective components of A. bidentata and disease OP. Cytoscape 3.6.1 software and STRING database were used to construct and analyze the “drug-component- disease-target” network and protein-protein interaction (PPI) network; KEGG pathway enrichment analysis was conducted by using DAVID bioinformatics resource database. RESULTS: A total of 19 effective components were screened from A. bidentata, and there were 32 intersecting targets between effective components and disease OP. In “drug-component-disease-target” network, there were 45 nodes [1 for A. bidentata, 1 for OP, 11 for effective components (8 of the 19 effective components had no corresponding OP target), 32 for intersecting targets] and 119 edges between nodes; quercetin, kaempferol, wogonin, baicalein and palmatine were important effective components. In PPI network, there were 31 nodes (1 of 32 intersecting targets was not associated with other proteins) and 212 edges, among which IL6, ESR1, MAPK1, IL8 and MAPK14 were the core targets of the network. There were 67 KEGG enrichment pathways, including rheumatoid arthritis, hepatitis B, Toll-like receptor signaling pathway, PI3K/Akt signaling pathway, JAK/STAT signaling pathway, NF-κB signaling pathway and so on. CONCLUSIONS: The main potential effective components of A. bidentata in the treatment of OP are quercetin, kaempferol, wogonin, baicalein and palmatine, the mechanism of which may be associated with cell differentiation and apoptosis, metabolism, inflammation reaction, etc. It has multi-component, multi-target and multi-system chara- cteristics., 百拇医药(赵杰 许波 刘金豹 梁学振 张凯博 陈帅 刘雨晴 李刚)
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