基于网络药理学与分子对接技术探究泽兰替代泽泻治疗心力衰竭的药效基础  

Exploration on the pharmacological basis of Lycopi Herba as alternative of Alismatis Rhizoma for the treatment of heart failure based on network pharmacology and molecular docking techniques

作　　者：刘思雨 石玉姣 刘永成 梁小雨 杨晨光 乔文博 董国菊[1,3] Liu Siyu;Shi Yujiao;Liu Yongcheng;Liang Xiaoyu;Yang Chenguang;Qiao Wenbo;Dong Guoju(Department of CardiologyⅠ,Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091,China;Graduate School,China Academy of Chinese Medical Sciences,Beijing 100091,China;National Clinical Research Center for Chinese Medicine Cardiology,Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091,China)

机构地区：[1]中国中医科学院西苑医院心血管一科,北京100091 [2]中国中医科学院研究生院,北京100700 [3]国家中医心血管病临床医学研究中心,北京100091

出　　处：《国际中医中药杂志》2024年第8期1045-1052,共8页International Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金(82074423);中国中医科学院科技创新重大攻关项目(CI2021A00903)。

摘　　要：目的采用网络药理学和分子对接探讨泽兰能否替代泽泻治疗心力衰竭。方法利用TCMSP筛选泽兰及泽泻有效成分, 通过SwissTargetPrediction数据库预测有效成分潜在靶点。通过GeneCards、OMIM、DisGeNET数据库收集心力衰竭相关靶点, 利用Venny 2.1.0构建泽兰/泽泻与心力衰竭的交集靶点韦恩图, 用STRING数据库构建交集靶点PPI网络, Cytoscape 3.9.1软件筛选得到泽兰/泽泻治疗心力衰竭的关键靶点, 并构建"成分-交集靶点"网络。使用Metascape对交集靶点进行GO功能和KEGG通路富集分析。采用分子对接技术评价活性成分与关键靶点的亲和力。结果泽兰主要作用于HMGCR、CYP27B1等关键靶点, 而泽泻作用靶点更为广泛, 如PPARA、JAK2等。两者共有关键靶点包括HMGCR、ESR1等, 主要参与胆固醇合成、类固醇激素合成等生物学机制。富集通路分析显示, 两者在类固醇代谢等方面具有共性, 而泽泻更倾向通过调节蛋白磷酸化、调控PI3K-Akt信号通路等治疗心力衰竭, 泽兰治疗心力衰竭特有靶点CHRM4, 显示出泽兰治疗心力衰竭的特有机制可能为调节血压、心肌保护等。结论泽兰和泽泻在心力衰竭治疗中具有一定共性, 但泽泻作用于更多靶点和信号通路, 因此可能具有更广泛的药效。鉴于泽泻的肾毒性, 建议治疗心力衰竭合并肾功能不全、早期心力衰竭方面可考虑以泽兰替代泽泻。Objective:To investigate whether Lycopi Herba can serve as a viable alternative to Alismatis Rhizoma in the treatment of heart failure(HF)through network pharmacology and molecular docking techniques.Methods:TCMSP database was used to filter active components of Lycopi Herba and Alismatis Rhizoma.SwissTargetPrediction database was used to predict potential targets.HF-related targets were collected from databases such as GeneCards,OMIM,and DisGeNET.Venny 2.1.0 was used to draw a Venn diagram illustrating the intersection of targets between Lycopi Herba and Alismatis Rhizoma and HF.A protein-protein interaction(PPI)network was established using the String database,and key targets for the treatment of HF with Lycopi Herba and Alismatis Rhizoma were selected using Cytoscape 3.9.1 software to construct a component-intersection target network.The intersection targets were then analyzed for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways using Metascape.Molecular docking techniques were used to evaluate the affinity between active components and key targets.Results:Lycopi Herba primarily targeted pivotal proteins such as HMGCR and CYP27B1,while Alismatis Rhizoma had a broader target spectrum,including PPARA,JAK2,among others.Shared key targets between the two included HMGCR and ESR1,which were primarily involved in cholesterol synthesis and steroid hormone biosynthesis.Enrichment pathway analysis showed similarities in steroid metabolism between the two;Alismatis Rhizoma,however,was more likely to act through protein phosphorylation regulation and modulating the PI3K-Akt signaling pathway for HF treatment.A unique target for Lycopi Herba in treating HF was CHRM4,indicating its potential for blood pressure regulation and myocardial protection.Conclusions:Both Lycopi Herba and Alismatis Rhizoma exhibit certain commonalities in the treatment of HF,but Alismatis Rhizoma has a wider range of targets and signaling pathways,implying more extensive therapeutic potential.However,considering the nephrot

关 键 词：泽兰 泽泻 心力衰竭 网络药理学 分子对接技术 

分 类 号：R285[医药卫生—中药学]