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基于网络药理学和分子对接技术探讨加味八珍汤治疗慢性脑循环功能不全的活性成分及作用机制。

Exploring the active components and mechanism of modified bazhen decoction in treatment of chronic cerebral circulation insufficiency based on network pharmacology and molecular docking.

机构信息

Emergency Department, Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, China.

Graduate College, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, China.

出版信息

Medicine (Baltimore). 2023 Jul 21;102(29):e34341. doi: 10.1097/MD.0000000000034341.

Abstract

Modified bazhen decoction (MBZD) is a classical Chinese medicine formula with potential efficacy in the treatment of chronic cerebral circulation insufficiency (CCCI), and its main components and potential mechanisms are still unclear. The study aimed to investigate the active ingredients and mechanism of action of MBZD in treating CCCI through network pharmacology combined with molecular docking. The chemical composition and targets of 11 Chinese herbs in MBZD were retrieved utilizing the traditional Chinese medicine systems pharmacology database and analysis platform platform, and the targets for CCCI were screened by Genecards, online mendelian inheritance in man, therapeutic target database, and comparative toxicogenomics database databases. The targets were genetically annotated with the Uniprot database. We created a compound-target network employing Cytoscape software and screened the core targets for the treatment of CCCI by CytoNCA clustering analysis; the AutoDock Vina program performed molecular docking study of crucial targets. One thousand one hundred ninety-one active compounds were obtained, 2210 corresponding targets were predicted, 4971 CCCI-related targets were obtained, and 136 intersecting genes were identified between them. The central core targets were IL6, MAPK14, signal transducer and activator of transcription 3, RELA, VEGFA, CCND1, CASP3, AR, FOS, JUN, EGFR, MAPK1, AKT1, MYC, and ESR1; gene ontology functional enrichment analysis yielded 911 gene ontology items (P < .01), while Kyoto Encyclopedia of Genes and Genomes pathway enrichment yielded 138 signal pathways (P < .01), primarily including oxidative reactions, vascular regulation, apoptosis, and PI3K-Akt signaling pathway. The molecular docking results showed that the core active component of MBZD had good binding with the main target. This research initially uncovered the mechanism of action of MBZD via multi-component-multi-target-multi-pathway for the treatment of CCCI, providing the theoretical basis for the clinical application of MBZD.

摘要

修改后的八珍汤(MBZD)是一种经典的中药方剂,具有治疗慢性脑循环不全(CCCI)的潜在功效,但其主要成分和潜在机制仍不清楚。本研究旨在通过网络药理学结合分子对接技术,探讨 MBZD 治疗 CCCI 的活性成分和作用机制。利用中药系统药理学数据库和分析平台(TCMSP)检索 MBZD 中 11 种中药的化学成分和靶点,通过 Genecards、在线 Mendelian 遗传在线、治疗靶点数据库和比较毒理学基因组数据库(CTD)筛选 CCCI 靶点,利用 Uniprot 数据库对靶点进行基因注释。我们使用 Cytoscape 软件创建了一个化合物-靶标网络,并通过 CytoNCA 聚类分析筛选出治疗 CCCI 的核心靶标;AutoDock Vina 程序对关键靶标进行了分子对接研究。共获得 1191 个活性化合物,预测了 2210 个相应的靶点,获得了 4971 个 CCCI 相关靶点,从中鉴定出 136 个相交基因。核心靶标为 IL6、MAPK14、信号转导和转录激活因子 3、RELA、VEGFA、CCND1、CASP3、AR、FOS、JUN、EGFR、MAPK1、AKT1、MYC 和 ESR1;基因本体论功能富集分析得到 911 个基因本体论项目(P<0.01),京都基因与基因组百科全书通路富集得到 138 个信号通路(P<0.01),主要包括氧化反应、血管调节、细胞凋亡和 PI3K-Akt 信号通路。分子对接结果表明,MBZD 的核心活性成分与主要靶标具有良好的结合性。本研究初步揭示了 MBZD 治疗 CCCI 的多成分-多靶点-多途径作用机制,为 MBZD 的临床应用提供了理论依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9766/10662881/f4d952734d7c/medi-102-e34341-g001.jpg

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