摘要
目的采用网络药理学及分子对接技术探讨丹参治疗缺血性肠病的作用机制。方法运用TCMSP数据库获得丹参的有效成分和预测靶点,并在UniProt数据库中进行标准化处理,从而获得相应的药物靶点基因。利用GeneCards和OMIM数据库获得缺血性肠病的靶点基因。将药物的靶点基因及疾病的靶点基因导入韦恩图制作分析平台获得丹参治疗缺血性肠病的潜在作用靶点。利用Cytoscape3.8.2软件构建“药物-成分-靶点-疾病”网络。将潜在的作用靶点导入STRING数据库进行蛋白质相互作用(PPI)网络分析。运用Metascape数据库对潜在作用靶点进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路分析。最后运用AutoDock vina、PyMOL等软件对丹参有效化学成分和关键的靶点基因进行对接验证。结果共获得了65个丹参的活性化合物成分,139个丹参的作用靶点基因和2799个缺血性肠病的作用靶点基因,其中丹参与缺血性肠病共同作用靶点为84个。构建网络发现木犀草素、丹参酮ⅡA、新隐丹参酮Ⅱ等为丹参作用于缺血性肠病的主要化合物成分。通过PPI网络分析发现蛋白激酶B1(Akt1)、肿瘤坏死因子(TNF)、雌激素受体1(ESR1)、原癌基因(JUN)和溶质载体家族6成员3(SLC6A3)等为关键的靶点基因。富集结果显示细胞对氮化合物的反应、细胞对有机环化合物的反应和细胞对有机氮化合物的反应等生物学过程调控脂质与动脉粥样硬化、流体剪切应力与动脉粥样硬化、磷脂酰肌醇3激酶(PI3K)/Akt信号通路、环鸟苷酸-蛋白激酶G(cGMP-PKG)信号通路、TNF信号通路等信号通路对缺血性肠病起到治疗作用。分子对接的结果表明丹参的有效化学成分和缺血性肠病的靶点基因具有良好的结合性。结论丹参可能通过木犀草素、丹参酮ⅡA、新隐丹参酮Ⅱ等有效成分,作用于Akt1、TNF和ESR1等核心靶点基因,调控脂质与动脉粥样硬化、流体剪切应力与动脉粥样硬化等信号通路对缺血性肠病起到治疗作用。
Objective To investigate the mechanism of action of Salvia miltiorrhiza in treatment of ischemic enteropathy by using network pharmacology and molecular docking technology.Methods The active components and predicted targets of Salvia miltiorrhiza were obtained by TCMSP database,and standardized in UniProt database to obtain the corresponding drug target genes.Target genes of ischemic bowel disease were obtained by GeneCards and OMIM databases.Drug target genes and disease target genes were introduced into the Venn diagram analysis platform to obtain potential targets of Salvia miltiorrhiza in treatment of ischemic bowel disease.Build a"Drug-ingredient-target-disease"network using Cytoscape3.8.2 software.Potential targets were imported into STRING database for protein interaction(PPI)network analysis.Metascape database was used for GO functional enrichment analysis and KEGG pathway analysis for potential targets.Finally,AutoDock vina,PyMOL and other software were used to analyze and verify the effective chemical components and key target genes of Salvia miltiorrhiza.Results A total of 65 active compounds of Salvia miltiorrhiza,139 target genes of Salvia miltiorrhiza and 2799 target genes of ischemic bowel disease were obtained,among which 84 target genes of Salvia miltiorrhiza and ischemic bowel disease were combined.Network construction revealed that luteolin,tanshinone IIA,and neocryptotanshinone II were the main compound components of Salvia miltiorrhiza acting in ischemic bowel disease.Aktl,TNF,ESRI,JUN,and SLC6A3 were identified as key target genes by PPI network analysis.The enrichment results showed that biological processes such as cellular response to nitrogen compounds,cellular response to organocyclic compounds,and cellular response to organic nitrogen compounds regulated lipids and atherosclerosis,fluid shear stress and atherosclerosis,PI3K/Akt signaling pathway,cGMP PKG signaling pathway,and TNF signaling pathway signaling pathways play a therapeutic role in ischemic bowel disease.The results of molecular docking indicated that the active chemical components of Salvia miltiorrhiza and the target genes of ischemic enteropathy have good binding.Conclusion Salvia miltiorrhiza may act on core target genes such as Aktl,TNF,and ESR1 to regulate lipids and atherosclerosis,fluid shear stress and atherosclerosis,through the active ingredients such as luteolin,tanshinone IIA and neocryptotanshinone II and other signaling pathways play a therapeutic role in ischemic bowel disease.
作者
陈淑妮
何海滨
雷孝文
何国新
王春鹏
李峰
CHEN Shuni;HE Haibin;LEI Xiaowen;HE Guoxin;WANG Chunpeng;LI Feng(Shenzhen Hospital(Longgang),Beijing University of Chinese Medicine,Shenzhen 518100,China;Beijing University of Chinese Medicine,Beijing 100029,China)
出处
《现代药物与临床》
CAS
2024年第9期2243-2253,共11页
Drugs & Clinic
基金
深圳市龙岗区经济与科技发展专项资金医疗卫生科技计划项目(LGWJ2021-75)。
关键词
丹参
缺血性肠病
网络药理学
分子对接
木犀草素
丹参酮ⅡA
新隐丹参酮Ⅱ
Salvia miltiorrhiza
ischemic enteropathy
network pharmacology
molecular docking
luteolin
tanshinone IIA
neocryptotanshinone II
