摘要
应用网络药理学和分子对接研究方法探讨昆明山海棠治疗糖尿病肾病的作用机制。利用TCSMP数据库搜集昆明山海棠的有效成分和靶点,通过GeneCards、GAD、OMIM、TTD等数据库查找糖尿病肾病相关的靶点,采用STRING平台构建PPI网络,应用Cytoscape软件对昆明山海棠治疗糖尿病肾病的作用靶点与有效成分构建可视化“药物-活性成分-靶点-通路-疾病”网络模型,预测昆明山海棠治疗糖尿病肾病的潜在靶标,通过DAVID数据库对关键靶点进行GO及KEGG分析,利用Autodock软件对网络药理学结果进行初步验证。从数据库中筛选出昆明山海棠有效成分15个,相对应的有效靶点123个;筛选出糖尿病肾病相关靶点11 119个。昆明山海棠有效成分作用靶点与糖尿病肾病靶点存在65个共有靶点分子,GO分析结果表明,昆明山海棠主要通过RNA聚合酶Ⅱ转录因子、类固醇激素受体、雄激素受体等生物学功能特性治疗DKD。KEGG富集分析结果显示,昆明山海棠的药理作用与mTOR信号通路、癌症通路、神经活性配体受体相互作用、叶酸一碳库、抗叶酸抗性、化学致癌-受体激活等信号通路等有关。分子对接结果表明,昆明山海棠中关键性化合物(如山海棠二萜内酯A、雷公藤红素等)的潜在靶标可能是SOAT1、DHFR等。其中SOAT1与山海棠二萜内酯A具有最高的结合能,可能在治疗中起重要作用。昆明山海棠可能通过调控SOAT1、DHFR靶点直接或间接参与调节细胞免疫、炎症、细胞凋亡等作用机制,对糖尿病肾病有潜在的治疗作用。
To explore the mechanism of the traditional Chinese medicine(TCM) Tripterygium Hypoglaucum in the treatment of diabetic kidney disease(DKD) based on network pharmacology and molecular docking technology, the traditional Chinese medicine systems pharmacology database and analysis platform was used to screen the components and targets of Tripterygium Hypoglaucum.GeneCards, GAD,OMIM and TTD databases were used to explore the targets related to DKD.String platform were used to construct PPI network, and Cytoscape software were used to construct a visual “drug-active ingredient-target-pathway-disease” network model on the targets and active ingredients of Tripterygium Hypoglaucum in the treatment of DKD,and to predict the potential targets of Tripterygium Hypoglaucum in the treatment of DKD.GO and KEGG were analyzed by DAVID database.AutoDock software was used to dock the active ingredients and core protein targets.According to the principle of oral availability and drug similarity, 15 effective components and 123 effective targets were selected from Tripterygium Hypoglaucum by the database.A total of 11 119 targets related to DKD were selected.There are 65 common target molecules of active components of Tripterygium Hypoglaucum and diabetic kidney disease.GO analysis result showed that Tripterygium Hypoglaucum treat DKD mainly by RNA polymerase II transcription factor activity, steroid binding, and rogen binding and other biological functional characteristics.KEGG analysis result showed that key signaling pathways mainly include mTOR signaling pathway, pathways in cancer, one carbon pool by folate, antifolate resistance, neuroactive ligand-receptor interaction, etc.Molecular docking simulation was performed, the results showed that the potential targets of key compounds(Hypodiolide A,Tripterine, etc.) in Tripterygium Hypoglaucum may be SOAT1,DHFR,etc.Among which SOAT1 with Hypodiolide A have the highest degree, indicating that they may play an important role in the pathological mechanism.Tripterygium Hypoglaucum may directly or indirectly participate in the regulation of cellular immunity, inflammation, apoptosis and other mechanisms by regulating SOAT1 and DHFR targets, and has potential therapeutic effects on DKD.
作者
郑威
商海涛
庞欣欣
彭紫凝
王学艺
肖明芝
陈双琴
ZHENG Wei;SHANG Hai-tao;PANG Xin-xin;PENG Zi-ning;WANG Xue-yi;XIAO Mingzhi;CHEN Shuang-qin(The Second Clinical Medical College of Henan University of Traditional Chinese Medicine,Zhengzhou 450046,China;Department of Nephropathy,Henan Provincial Hospital of Traditional Chinese Medicine(The Second Hospital Affiliated to Henan University of Chinese Medicine),Zhengzhou 450002,China;Guangxi University of Chinese Medicine,Nanning 530000,China)
出处
《药物生物技术》
CAS
2023年第1期12-18,共7页
Pharmaceutical Biotechnology
基金
国家自然科学基金(No.81900627)
河南省科技攻关项目(No.202102310505)
河南省自然科学基金(No.202300410256)。
关键词
昆明山海棠
糖尿病肾病
网络药理学
分子对接
潜在靶点
作用机制
中药
Tripterygium Hypoglaucum
Diabetic kidney disease
Network pharmacology
Molecular docking
Potential target
Action mechanism
Traditional Chinese medicine
作者简介
郑威(1994-),女,河南郑州人,硕士研究生,河南中医药大学,研究方向:中医药治疗慢性肾脏病的研究,E-mail:kit3085zw@163.com;通信作者:庞欣欣(1986-),男,河南平顶山人,副主任医师,博士,硕士生导师,河南省中医院肾病科,研究方向:中医药治疗慢性肾脏病的研究,E-mail:doctorpang@aliyun.com。
