温通膏治疗膝骨关节炎的网络药理学分析  

Network Pharmacology Analysis of Wentong Ointment for the Treatment of Knee Osteoarthritis

作　　者：张力文 翁家贤 吴涵 黄晓冰 钟碧莲 吴雪茹 ZHANG Liwen;WENG Jiaxian;WU Han;HUANG Xiaobing;ZHONG Bilian;WU Xueru(The Third Clinical Medical School of Guangzhou University of Chinese Medicine,Guangzhou 510006 Guangdong,China;The First Clinical Medical School of Guangzhou University of Chinese Medicine,Guangzhou 510006 Guangdong;The Third Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510378 Guangdong,China)

机构地区：[1]广州中医药大学第三临床医学院,广东广州510006 [2]广州中医药大学第一临床医学院,广东广州510006 [3]广州中医药大学第三附属医院,广东广州510378

出　　处：《中药新药与临床药理》2022年第9期1228-1235,共8页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：广东省中医药局科研项目(粤中医办函[2015]102号,20183007,20201169,20211212);广州市海珠区科技计划项目(海科工商信计2018-95)。

摘　　要：目的 基于网络药理学方法探讨温通膏(补骨脂、续断、干姜等)治疗膝骨关节炎(KOA)的潜在作用机制。方法 利用中药系统药理学分析平台(TCMSP)和BATMAN-TCM数据库筛选温通膏的活性成分及其作用靶点;利用GeneCards、OMIM和DisGeNet数据库检索KOA疾病相关靶点;通过Venny 2.1.0在线平台对温通膏的活性成分作用靶点与KOA疾病相关靶点映射取交集,即得温通膏治疗KOA的关键靶点(共同靶点);将共同靶点导入STRING平台构建蛋白相互作用(PPI)网络;利用Cytoscape 3.8.0软件构建“活性成分-关键靶点”网络;将共同靶点导入DAVID数据库,进行GO功能及KEGG通路富集分析,并利用Cytoscape 3.8.0软件构建“关键靶点-信号通路”网络。结果 共筛选得到103个活性成分及其作用靶点共348个;得到温通膏治疗KOA的关键靶点(共同靶点)147个;PPI网络分析得到AKT1、TNF、IL6、TP53、IL1B、VEGFA、JUN等核心靶点;槲皮素、β-谷甾醇、山柰酚、豆甾醇等活性成分可能是温通膏治疗KOA的核心成分;GO功能富集分析得到612个生物过程(BP),77个细胞组分(CC),104个分子功能(MF);得到152条KEGG信号通路,主要涉及糖尿病并发症中的AGE-RAGE信号通路、TNF信号通路等。结论 温通膏可能通过槲皮素、β-谷甾醇、山柰酚等主要活性成分,作用于AKT1、TNF、VEGFA等核心靶点,通过AGE-RAGE、TNF等信号通路,协同发挥对KOA的治疗作用。Objective To explore the potential mechanism of action of Wentong Ointment(main components include Fructus Psoraleae,Radix Dipsaci,Rhizoma Zingiberis,etc.)in the treatment of knee steoarthritis(KOA)based on network pharmacological approach. Methods The active components of Wentong Ointment and its targets were screened using the TCMSP and BATMAN-TCM databases;the KOA disease-related targets were retrieved using GeneCards,OMIM and DisGeNet databases;the key targets(common targets)of Wentong Ointment for KOA were obtained by mapping the intersection of the active components targets and the KOA-related targets through the Venny2.1.0 online platform;the common targets were imported into the STRING platform to build a target protein-protein interaction(PPI)network;Cytoscape 3.8.0 software was used to build an "active components-key target" network;the common targets were imported into the DAVID database for GO function and KEGG pathway enrichment analysis,and the "key target-signalling pathway" network was built using Cytoscape 3.8.0 software. Results A total of 103 active components and 348 targets were screened;a total of 147 key targets(common targets)were obtained for the treatment of KOA with Wentong Ointment;the core targets such as AKT1, TNF, IL6, TP53, IL1B,VEGFA and JUN were obtained by PPI network analysis;the active components such as quercetin,β-sitosterol,kaempferol and stigmasterol may be the core components of Wentong Ointment for the treatment of KOA;GO functional enrichment analysis was obtained by 612 biological processes(BP), 77 cellular components(CC),104 molecular functions(MF);152 KEGG signaling pathways were obtained, mainly involving AGE-RAGE signaling pathway and TNF signaling pathway in diabetic complications. Conclusion Wentong Ointment may act on the core targets of AKT1,TNF and VEGFA through quercetin,β-sitosterol,kaempferol and other major active components,and synergistically exert therapeutic effects on KOA through AGE-RAGE,TNF and other signalling pathways.

关 键 词：温通膏 膝骨关节炎 网络药理学 作用机制 槲皮素 Β-谷甾醇 山柰酚 

分 类 号：R285.5[医药卫生—中药学] R857.3[医药卫生—中医学]