基于网络药理学、分子对接和实验研究探讨犀角地黄汤治疗血热型银屑病的作用机制  

Exploring the Mechanism of Xijiao Dihuang Decoction in Treating Blood-heat Psoriasis Based on Network Pharmacology,Molecular Docking and Experimental Research

作　　者：俞晨卉 蓝宏荣 吴燕瑜 邱桂荣[2] 李晓健 周楠 张灵金 YU Chenhui;LAN Hongrong;WU Yanyu;QIU Guirong;LI Xiaojian;ZHOU Nan;ZHANG Lingjin(Graduate School of Jiangxi University of Chinese Medicine,Nanchang 330004,China;The Affiliated Hospital of Jiangxi University of Chinese Medicine,Nanchang 330006,China;Shenzhen Hospital of Shanghai University of Traditional Chinese Medicine,Shenzhen 518001,China.)

机构地区：[1]江西中医药大学研究生院,南昌330004 [2]江西中医药大学附属医院,南昌330006 [3]上海中医药大学深圳医院,广东深圳518001

出　　处：《江西中医药大学学报》2024年第3期67-74,共8页Journal of Jiangxi University of Chinese Medicine

基　　金：江西中医药大学科技创新团队项目(CXTD22009)。

摘　　要：目的:利用网络药理学、分子对接技术,探讨犀角地黄汤治疗血热型银屑病的活性成分和分子机制,并用实验进行验证。方法:采用TCMID获取方中4味药的化学成分,通过Swiss Target Prediction获取相关作用靶点。在OMIM数据库和GeneCards数据库中搜集银屑病作用靶点,筛选出交集靶点。运用String数据库和Cytoscape 3.9.1绘制PPI网络图,并用插件Centiscape 2.2拓扑分析得到核心靶点。借助Metascape数据库对交集靶点进行GO和KEGG分析,运用Autodock1.5.7软件以及Pymol软件对关键成分和度值排名前5的核心靶点进行分子对接验证以及可视化分析。综合分析后,选择结合能稳定的靶标Akt1进行动物实验验证。结果:犀角地黄汤治疗银屑病的关键活性成分有黄芩素、芍药苷、谷甾醇、槲皮素、鞣花酸等。从靶蛋白的角度分析,核心靶点有GAPDH、TP53、Akt1、IL-6、TNF、GFR等。GO富集分析提示主要涉及炎症反应的调节、miRNA代谢过程的调控、调节氧化还原酶/蛋白激酶活性等生物过程。KEGG通路主要包括乙型肝炎、癌症的发病途径、PI3K-Akt信号通路、MAPK信号通路等。分子对接结果表明活性成分黄芩素、芍药苷、谷甾醇、槲皮素、鞣花酸与核心靶点GAPDH、TP53、Akt1、IL-6、TNF,均有较好结合活性。动物实验结果显示犀角地黄汤能改善银屑病小鼠皮损,提高PI3K/Akt的表达。结论:犀角地黄汤治疗血热型银屑病可能是多成分、多靶点、多通路的过程,并通过动物实验进一步验证了该复方治疗银屑病可能是通过PI3K-Akt信号通路而发挥作用。Objective:To explore the active components and molecular mechanisms of Xijiao Dihuang Decoction for the treatment of blood-heat psoriasis using network pharmacology,molecular docking techniques and experimental research.Methods:TCMID was used to obtain the chemical compositions of the four herbs in the formula,and the relevant targets of action were obtained by Swiss Target Prediction.The psoriasis targets were collected in OMIM database and GeneCards database,and the intersecting targets were screened.The PPI network was mapped using String database and Cytoscape 3.9.1,and the core targets were analyzed using the plug-in Centiscape 2.2 topology.GO and KEGG analyses of the intersecting targets were performed with the help of Metascape database,and molecular docking validation and visualization of the results were carried out for the key components and the core targets with the top 5 degree values using Autodock 1.5.7 software as well as Pymol software.After comprehensive analysis,Akt1,a target with stable binding energy,was selected for validation in animal experiments.Results:The key active ingredients of Xijiao Dihuang Decoction for the treatment of psoriasis are baicalein,paeoniflorin,glutathione,quercetin,ellagic acid and so on.From the perspective of target proteins,the core targets are GAPDH,TP53,Akt1,IL-6,TNF,GFR and so on.GO enrichment analysis suggests that it is mainly involved in the regulation of inflammatory response,regulation of miRNA metabolic process,regulation of oxidoreductase/protein kinase activity,and other biological processes.KEGG pathways mainly include the pathways for the pathogenesis of hepatitis B,cancer,PI3K-Akt signaling pathway MAPK signaling pathway,etc.The molecular docking results showed that the active ingredients baicalein,paeoniflorin,glutathione,quercetin,ellagic acid had good binding activities with the core targets GAPDH,TP53,Akt1,IL-6,and TNF.The results of animal experiments showed that Xijiao Dihuang Decoction improved skin lesions and increased PI3K/Akt expression in p

关 键 词：犀角地黄汤 银屑病 网络药理 分子对接 动物实验 

分 类 号：R285[医药卫生—中药学]