基于网络药理学与分子对接探讨温胆汤对心力衰竭合并抑郁共病同治机制  

Exploring the mechanism of treating heart failure with depression by Wendan Tang based on network pharmacology and molecular docking

作　　者：丁志强 杨林 朱熹 邓梦婷 王陵军[3] 冼绍祥[3] 方红城 李志芳 DING Zhiqiang;YANG Lin;ZHU Xi;DENG Mengting;WANG Lingjun;XIAN Shaoxiang;FANG Hongcheng;LI Zhifang(Shenzhen Integrated Chinese and Western Medicine Hospital,Guangzhou University of Chinese Medicine,Shenzhen 518104,China)

机构地区：[1]广州中医药大学深圳市中西医结合医院研究生培养基地,深圳518104 [2]深圳市中西医结合医院心血管病科 [3]广州中医药大学岭南医学研究中心

出　　处：《环球中医药》2024年第7期1281-1290,共10页Global Traditional Chinese Medicine

基　　金：广东省中医药局课题(20211343、20231297);深圳市“医疗卫生三名工程”资助项目(SZZYSM202106006)。

摘　　要：目的基于网络药理学探讨温胆汤对心力衰竭合并抑郁共病同治机制,并通过分子对接初步验证。方法通过TCMSP数据库与文献搜索得到温胆汤有效成分并预测作用靶点;在GeneCards、OMIM、DisGeNET以及TTD数据库搜索心力衰竭、抑郁症相关疾病靶点,与温胆汤作用靶点取交集。通过STRING平台完成交集靶点的蛋白质相互作用网络的构建并预测核心靶点,并对交集靶点进行基因本体注释及京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析,最后利用分子对接验证核心成分及核心靶点的结合能力。结果温胆汤治疗心力衰竭合并抑郁的核心成分为木犀草素、川陈皮素、β-谷甾醇、黄芩苷、豆甾醇等,核心靶点主要包括肿瘤坏死因子、白细胞介素-6、蛋白激酶B1、白细胞介素-1β、肿瘤蛋白p53等,通过KEGG主要富集在晚期糖基化终产物及其受体、磷脂酰肌醇-3激酶/蛋白激酶B、环磷酸腺苷、丝裂原活化蛋白激酶等信号通路。分子对接结果表明,木犀草素等核心成分与肿瘤坏死因子、白细胞介素-6等核心靶点的结合活性较好。结论温胆汤可能通过抑制炎症反应及氧化应激反应、调节神经递质的释放等方面来治疗心力衰竭合并抑郁。Objective Exploring the mechanism of the combined treatment of heart failure and depression by Wendan Tang based on network pharmacology,and preliminary validation through molecular docking.Methods The effective ingredients of Wendan Tang were obtained through the TCMSP database and literature search,and their target proteins were predicted.Disease-related targets for heart failure and depression were searched in GeneCards,OMIM,DisGeNET,and TTD databases,and the intersection of these targets with the targets of Wendan Tang were obtained.The protein-protein interaction(PPI)network of the intersected targets was constructed and core targets were predicted using the STRING platform.Gene ontology(GO)annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed on the intersected targets.Finally,molecular docking was used to verify the binding ability of core ingredients and core targets.Results The core ingredients of Wendan Tang in treating heart failure combined with depression were identified as Luteolin,nobiletin,Beta-sitosterol,baicalein,and Stigmasterol.The core targets mainly included TNF,IL-6,AKT1,IL-1β,and TP53.KEGG analysis revealed enrichment in signaling pathways such as AGE-RAGE,PI3K-AKT,cAMP,and MAPK.Molecular docking results showed that the core ingredients,such as Luteolin,exhibited good binding activity with core targets,including TNF and IL-6.Conclusion Wendan Tang may potentially treat heart failure combined with depression by inhibiting inflammatory reactions and oxidative stress,as well as regulating the release of neurotransmitters.

关 键 词：温胆汤 心力衰竭 抑郁 网络药理学 分子对接 富集分析 信号通路 作用机制 

分 类 号：R259[医药卫生—中西医结合]