基于网络药理学探讨骨碎补治疗骨质疏松症的作用机制
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篇名: 基于网络药理学探讨骨碎补治疗骨质疏松症的作用机制
TITLE:
摘要: 目的:探讨骨碎补治疗骨质疏松(OP)的作用机制。方法:采用中药系统药理学成分分析平台(BATMAN-TCM)数据库获得骨碎补的活性化合物及其作用靶点,再通过GeneCards数据库获得相关化合物靶点,取两者交集得到骨碎补作用靶点。通过TTD、DrugBank、OMIM、GAD、PharmGKB、CTD数据库获得OP疾病相关靶点,与骨碎补作用靶点取交集后获得骨碎补-OP疾病交集靶点。运用STRING在线数据库构建蛋白相互作用(PPI)网络,再通过Cytoscape 3.6.1软件进行分析获得关键靶点,并进行可视化展示。借助DAVID在线工具进行交集靶点的基因本体论(GO)分析。通过在线分析工具KOBAS进行KEGG通路富集分析,筛选出显著富集的通路(P<0.05)。通过MCC算法进行关键基因的筛选。结果:共获得骨碎补活性化合物7个,骨碎补-OP疾病交集靶点136个。GO分析结果显示,上述交集靶点的生物途径主要包括化学反应、类固醇代谢过程、细胞对化学刺激的应答等;细胞组分主要包括细胞外间隙、胞外区部分、细胞质等;分子功能主要有血红素结合、四吡咯结合、单氧酶活性等。KEGG通路富集结果显示,上述靶点主要与骨代谢、内分泌、炎症、肿瘤、细胞凋亡等信号通路相关。通过MCC算法筛选得到关键基因30个,包括ALB、AKT1、JUN等(P≤1.96×10-9)。结论:骨碎补治疗OP的作用机制呈多靶点、多系统的特性,除了影响骨代谢相关途径还可影响体内多种代谢途径。
ABSTRACT: OBJECTIVE: To investigate the mechanism of Drynariae rhizoma in the treatment of osteoporosis (OP). METHODS: The active compounds and targets of D. rhizoma were obtained by using Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM database). The targets of relevant compounds were also obtained by GeneCards database, and targets of D. rhizoma were obtained by the combination of the two. The disease targets corresponding to OP were obtained by using TTD, DrugBank, OMIM, GAD, PharmGKB and CTD database. The D. rhizoma-OP disease intersection targets were obtained after intersecting with the target of D. rhizoma. PPI network was constructed by STRING online database, analyzed by using Cytoscape 3.6.1 software to obtain key targets and showed by network visualization. Gene ontology(GO) analysis of drug-disease intersection target were conducted by DAVID online tools. KEGG pathway enrichment analysis was conducted by KOBAS online tools to screen the significant enrichment pathway (P<0.05). The key genes were screened by MCC algorithm. RESULTS: There were 7 active compounds of D. rhizoma 136 intersection targets of D. rhizoma-OP disease. GO analysis results showed that the biological function of intersection target mainly included chemical reaction, steroid metabolic process as well as cellular response to chemical stimulus and so on; cell composition mainly included extracellular space, extracellular area and cytoplasm;molecular functions included heme binding, tetrapyrrole binding and monooxygenase activity, etc. KEGG pathway enrichment showed that above targets were mainly related to bone metabolism, endocrinology, inflammation, tumor, apoptosis, etc. Thirty key genes (such as ALB, AKT1, JUN, etc., P≤1.96×10-9) were screened by MCC algorithm. CONCLUSIONS: The mechanism of action of D. rhizoma in the treatment of OP is in multi-target and multi-system manner. In addition to influencing the related pathways of bone metabolism, it can also affect various metabolic pathways in vivo.
期刊: 2019年第30卷第10期
作者: 林适,吴潇烁,陈柏行,陈超,吴宇航,周琦石,何才勇
AUTHORS: LIN Shi,WU Xiaoshuo,CHEN Baihang,CHEN Chao,WU Yuhang,ZHOU Qishi,HE Caiyong
关键字: 骨碎补;骨质疏松症;作用机制;通路;靶点;网络药理学
KEYWORDS: Drynariae rhizoma; Osteoporosis; Mechanism; Pathway; Target; Network pharmacology
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