摘要
[目的]应用中药系统药理学数据库与分析平台(TCMSP)及小分子药物靶点预测在线平台(Swiss Target Prediction)和疾病基因组数据库,结合分子对接技术,预测巴戟天抗动脉粥样硬化(As)的靶点及信号通路。[方法]通过中药网络药理学数据库及小分子药物靶点预测在线平台挖掘巴戟天的有效成分及其所对应的靶点,利用GeneCards、OMIM、Disgenet、UniProt收集并筛选As相关的疾病基因靶点,获取交集基因,将其导入String 11.5数据库中,构建疾病-药物蛋白互作分析(String-PPI)网络图,利用Cytoscape 3.9.1软件对关键靶点网络进行可视化;此外,运用Metascape网络在线平台进行GO、KEGG富集挖掘出其抗As的分子靶点,并通过KEGG数据库绘制通路图。最后,使用Autodock vina 1.1.2软件对核心化合物及核心靶点基因进行分子对接验证。[结果]通过以上数据库共收集得到包括β-谷甾醇和蒽醌在内的17个有效药物化合物、73个核心靶点和1 450个关键疾病基因;取交集后得到巴戟天治疗As的35个核心基因;经String-PPI得到基因间有相互作用的SRC、PGTS2、TGFβ1、REN、ESR1、CASP3等32个基因;KEGG富集到75条信号通路,涉及脂质-动脉粥样硬化、晚期糖基化终末产物及受体、PI3K-Akt信号通路等相关通路;其中脂质-动脉粥样硬化通路主要涉及SRC、BCL2、BAX、CASP3、GSK3B、RXRA等6个靶基因。分子对接结果显示,巴戟天的主要化学成分与核心基因之间有较强的结合活性。[结论]巴戟天可能通过β-谷甾醇、蒽醌等主要有效化学成分调控SRC、PGTS2、TGFβ1、REN、RXRA、ESR1、CASP3等32个主要靶基因表达,减轻血管内皮炎症反应,抑制细胞增殖、迁移和凋亡,发挥抗As的作用。
Aim To predict the anti-atherosclerotic targets and signal pathways of Morinda officinalis by using traditional Chinese medicine system pharmacology,small molecule drug target prediction and disease genome database,and combined with the molecular docking technology.Methods The technology platform of Chinese medicine system pharmacology(TCMSP)and the online platform for small molecule drug target prediction(Swiss Target Prediction)were used to explore the active components of Morinda officinalis and the targets of its response.GeneCards,OMIM,Disgenet and UniProt were used to collect and screen the disease targets related to atherosclerosis.The intersection genes were obtained and imported into the String 11.5 database to construct the disease-drug protein-protein interaction(String-PPI)network map.Cytoscape 3.9.1 software was used to visualize key target networks.Then,GO and KEGG enrichment were performed using Metascape online platform to explore the molecular targets of anti-atherosclerosis,the pathway map was drawn through KEGG database.Finally,Autodock vina 1.1.2 software was used to verify the molecular docking of core compounds and target genes of Morinda officinalis.Results A total of 17 effective drug compounds includingβ-sitosterol and anthraquinone,73 core targets and 1450 key disease genes were collected from the above databases,then 35 core genes of Morinda officinalis acted on atherosclerosis were obtained after the intersection.32 genes including SRC,PGTS2,TGFβ1,REN,ESR1 and CASP3,were identified by String-PPI.KEGG enriched 75 signaling pathways,involving lipid-atherosclerosis,advanced glycosylation end products and receptors and PI3K-Akt signaling pathway,among which lipid-atherosclerosis pathway mainly involves six target genes such as SRC,BCL2,BAX,CASP3,GSK3B and RXRA.Molecular docking showed that the main chemical components of Morinda officinalis had strong binding activity with core genes.Conclusion Morinda officinalis can regulate the expression of 32 major genes including SRC,PGTS2,TGFβ1,REN,RXRA,ESR1,CASP3 throughβ-sitosterol,anthraquinone and other major chemical components,controls vascular endothelial inflammation and inhibits cell proliferation,migration and apoptosis,therefore plays the certain role of anti-atherosclerosis.
作者
罗才
吴林栩
朱星霖
揭伟
郭峻莉
LUO Cai;WU Linxu;ZHU Xinglin;JIE Wei;GUO Junli(Hainan Provincial Key Laboratory for Tropical Cardiovascular Diseases Research,the First Affiliated Hospital of Hainan Medical University,Haikou,Hainan 571199,China)
出处
《中国动脉硬化杂志》
CAS
2023年第8期654-662,共9页
Chinese Journal of Arteriosclerosis
基金
国家自然科学基金项目(82260083)
海南省重点研发社会发展专项(ZDYF2020214)。
关键词
动脉粥样硬化
巴戟天
网络药理学
分子对接
信号通路
atherosclerosis
Morinda officinalis
network pharmacology
molecular docking
signaling pathways
