基于网络药理学和分子对接探讨熊果酸治疗骨质疏松的分子机制
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篇名: 基于网络药理学和分子对接探讨熊果酸治疗骨质疏松的分子机制
TITLE: Molecular Mechanism of Ursolic Acid in the Treatment of Osteoporosis Based on Network Pharmacology and Molecular Docking
摘要: 目的:探讨熊果酸治疗骨质疏松症(OP)的潜在分子机制。方法:运用中药系统药理学分析平台数据库、PubMed数据库、UniProt数据库筛选单体化合物熊果酸的作用靶点基因,借助GeneCards数据库检索OP相关靶点基因,并运用Venny2.1在线作图工具获取成分-疾病的共有靶点基因;运用STRING数据库构建成分-疾病共有靶点基因的蛋白质-蛋白质相互作用关系(PPI)网络并进行拓扑学分析,筛选度值大于平均度值的核心靶点基因;使用DAVID数据库对成分-疾病共有靶点基因进行基因本体(GO)功能注释和KEGG通路富集分析。以核心靶点基因编码蛋白为受体、熊果酸为配体,采用AutoDockVina1.1.2软件进行分子对接。结果:共挖掘出熊果酸相关靶点基因55个、OP相关靶点基因4273个,两者共有靶点基因44个。上述共有靶点基因的PPI网络共包含节点44个、边513条,平均节点度值为23.3;核心靶点基因共24个,包括VEGFA、TP53、IL6、CASP3等。共富集到GO功能条目340个(校正后P值小于0.05),其中生物过程263个(涉及凋亡过程的负调控等)、分子功能25个(涉及蛋白质结合等)、细胞组分52个(涉及胞质溶胶等);共富集到KEGG信号通路90条(校正后P值小于0.05),如癌症通路、乙型肝炎、肿瘤坏死因子(TNF)信号通路、磷脂酰肌醇3激酶/蛋白激酶B(PI3K/Akt)信号通路等。熊果酸与TP53等6个核心靶点基因编码蛋白的结合能均低于-5kcal/mol,有较强的结合活性。结论:熊果酸对OP的治疗作用可能是通过调控VEGFA、TP53、IL6、CASP3、JUN等核心靶点基因,作用于癌症通路、乙型肝炎、TNF信号通路等多条关键通路而实现的。
ABSTRACT: OBJECTIVE:To explo re the potential molecular mechanism of ursolic acid in the treatment of osteoporosis (OP). METHODS:TCMSP,PubMed database and UniProt database were used to screen potential targets of monomer compound ursolic acid. OP related target genes were searched with GeneCards database. The common target genes of component-disease were obtained by Venny 2.1 online mapping tool. The protein-protein interaction (PPI)network of component-disease common target genes was constructed by using STRING database ,and topological analysis was carried out ;the core target genes ,whose degree value was greater than the average degree value ,were screened. GO functional annotation and KEGG pathway enrichment analysis of component-disease common target genes were carried out by DAVID database. AutoDock Vina 1.1.2 software was used for molecular docking ,using protein encoded by the core target gene as receptor and ursolic acid as ligand. RESULTS :A total of 55 ursolic acid related target genes and 4 273 OP related target genes were excavated ,with a total of 44 common target genes. PPI network with above common target genes included 44 nodes and 513 edges,with an average node degree of 23.3. There were 24 core target genes ,including VEGFA,TP53,IL6,CASP3. There were 340 GO functional items were enriched (corrected P< 0.05),including 263 biological processes (negative regulation of apoptosis ,etc.),25 molecular functions (protein binding ,etc.) and 52 cell components (cytosol,etc.). There were 90 KEGG signaling pathways (corrected P<0.05),such as tumor pathway , hepatitis B pathway ,TNF signaling pathway ,viral carcinogenesis and phosphatidylinositol 3 kinase/protein kinase B (PI3K-Akt) signaling pathway. The binding energy between ursolic acid and 6 proteins encoded by core target genes such as TP53 was lower than -5 kcal/mol,which had strong binding activity. CONCLUSIONS :The therapeutic effect of ursolic acid on OP may be achieved by regulating VEGFA,TP53,IL6,CASP3,JUN and other core target genes and acting on multiple key pathways such as cancer pathway , hepatitis B and TNF signaling
期刊: 2021年第32卷第17期
作者: 赵俊,孙加琳,刘洪玲,刘广伟,李祥鹏,仓怀芹,梁瑜,张传洲,韩冰,隋忠国
AUTHORS: ZHAO Jun,SUN Jialin,LIU Hongling, LIU Guangwei,LI Xiangpeng,CANG Huaiqin,LIANG Yu,ZHANG Chuanzhou,HAN Bing,SUI Zhongguo
关键字: 熊果酸;骨质疏松症;网络药理学;分子对接;分子机制
KEYWORDS: Ursolic acid ; Osteoporosis; Network
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