基于网络药理学和分子对接探究祖卡木颗粒治疗支气管哮喘的作用机制  

Mechanism and experimental validation of Zukamu granules in treatment of bronchial asthma based on network pharmacology and molecular docking

作　　者：候艳敏 徐梅[2] 张丽娟 李俞瑶 周文欣 王航宇 王金辉 刘冬[2] 张珂 HOU Yan-min;XU Mei;ZHANG Li-juan;LI Yu-yao;ZHOU Wen-xin;WANG Hang-yu;WANG Jin-hui;LIU Dong;ZHANG Ke(School of Pharmacy/Key Laboratory of Xinjiang Phytomedicine Resources and Utilization,Ministry of Education,Shihezi University,Shihezi Xinjiang 832002,China;First Affiliated Hospital of the Medical College,Shihezi University,Shihezi Xinjiang 832002,China;School of Pharmacy,Harbin Medical University,Harbin 150081,China)

机构地区：[1]石河子大学药学院/新疆植物药资源利用教育部重点实验室,新疆石河子832002 [2]石河子大学医学院第一附属医院,新疆石河子832002 [3]哈尔滨医科大学药学院,黑龙江哈尔滨150081

出　　处：《中国药理学通报》2024年第2期363-371,共9页Chinese Pharmacological Bulletin

基　　金：国家重大专项新药创制项目(No 2018ZX09735-005)。

摘　　要：目的利用网络药理学和分子对接技术预测祖卡木颗粒(zukamu granules,ZKMG)治疗支气管哮喘的作用机制,并通过体内实验验证预测结果。方法数据库检索ZKMG活性化合物、靶点以及潜在的支气管哮喘靶点,用ZKMG以及支气管哮喘的交集靶点构建药物-成分-靶点网络,构建蛋白-蛋白相互作用网络图(PPI),采用基因本体论(GO)和京都基因和基因组百科全书(KEGG)进行富集分析,并通过网络药理学结果进行分子对接。腹腔注射卵清蛋白(ovalbumin,OVA)建立支气管哮喘模型,经体内实验验证ZKMG对支气管哮喘的作用机制。结果ZKMG中含有194种潜在活性成分,关键成分包括槲皮素、山奈酚、木犀草素等;其治疗支气管哮喘的关键靶点有176个,靶点主要涉及的生物学过程包括信号传导、凋亡过程的负调控、血管生成,通过TNF、血管内皮生长因子A(VEGFA)、MAPK等信号通路对支气管哮喘发挥治疗作用。结论分子对接结果显示关键成分与对应靶点具有较好的结合活性。体内实验验证,ZKMG可改善支气管哮喘肺部炎症情况以及氧化应激水平,能够下调p-p38、p-ERK1/2、p-IκBα以及NF-κBp65的表达。ZKMG对支气管哮喘具有潜在的治疗作用。Aim To anticipate the mechanism of zuka-mu granules(ZKMG)in the treatment of bronchial asthma,and to confirm the projected outcomes through in vivo tests via using network pharmacology and molecular docking technology.Methods The database was examined for ZKMG targets,active substances,and prospective targets for bronchial asthma.The protein protein interaction network diagram(PPI)and the medication component target network were created using ZKMG and the intersection targets of bronchial asthma.The Kyoto Encyclopedia of Genes and Genomics(KEGG)and gene ontology(GO)were used for enrichment analysis,and network pharmacology findings were used for molecular docking.ovalbumin(OVA)intraperitoneal injection was used to create a bronchial asthma model,and in vivo tests were used to confirm how ZKMG affected bronchial asthma.Results There were 176 key targets for ZKMG′s treatment of bronchial asthma,most of which involved biological processes like signal transduction,negative regulation of apoptotic processes,and angiogenesis.ZKMG contained 194 potentially active components,including quercetin,kaempferol,luteolin,and other important components.Via signaling pathways such TNF,vascular endothelial growth factor A(VEGFA),cancer pathway,and MAPK,they had therapeutic effects on bronchial asthma.Conclusion Key components had strong binding activity with appropriate targets,according to molecular docking data.In vivo tests showed that ZKMG could reduce p-p38,p-ERK1/2,and p-IκB and NF-κBp65 expression and reduce lung inflammation and oxidative stress levels in bronchial asthma.

关 键 词：祖卡木颗粒 卵清蛋白 支气管哮喘 NF-κB/MAPK 网络药理学 分子对接 

分 类 号：R-332[医药卫生] R282.71R341R319R562.25