基于网络药理学和分子对接探讨番连化浊颗粒 治疗溃疡性结肠炎作用机制
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R336

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广东省自然科学基金项目(2022A1515011307)


Exploration on Action Mechanism of Fanlian Huazhuo Granules for Ulcerative Colitis Based on Network Pharmacology and Molecular Docking
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    目的:通过网络药理学方法联合GEO基因芯片的分析方法,探讨番连化浊颗粒(FHK) 治疗溃疡 性结肠炎(UC) 的作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP) 和本草组鉴平 台(HERB) 获取FHK的活性成分及对应靶点的基因,并利用Cytoscape软件构建“活性成分-药物靶点”调控 网络;通过基因表达综合数据库(GEO) 获得UC的差异表达基因;结合疾病的差异表达基因和药物的活性成 分进行交集靶点的确定,并利用STRING数据库进行蛋白互作网络(PPI) 的构建;对交集靶点进行基因本 体(GO) 功能和基因组百科全书(KEGG) 通路富集分析;根据筛选后的核心成分和核心靶点,利用Autodock Vina软件进行分子对接验证,初步验证核心成分与靶点的结合度。结果:共筛选得到FHK有效成分83种,对 应1 495个作用靶点;GEO数据得到UC差异表达基因973个;交集靶点41个为FHK治疗UC的潜在作用靶点。 根据GO和KEGG的结果可知,FHK作用于UC主要涉及对脂多糖的反应、对细菌分子的反应、细胞因子的活化 及其对信号通路的介导作用等生物进程,并主要作用于膜筏和膜微区,与肿瘤坏死因子、脂质和动脉粥样硬 化、白细胞介素-17信号通路密切相关。分子对接模拟结果显示FHK的活性成分与核心靶点之间具有较高的结 合度。结论:FHK治疗UC是通过多靶点、多途径、多通路共同作用实现的,其主要的作用机制可能集中在抗 炎及免疫调节上。

    Abstract:

    Abstract: Objective: To explore the action mechanism of Fanlian Huazhuo Granules(FHK) for ulcerative colitis (UC) by network pharmacology combined with Gene Expression Omnibus (GEO) gene chip analysis. Methods: The active components and corresponding target genes of FHK were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the HERB database; Cytoscape software was used to construct an "active component-drug target" regulatory network; differentially expressed genes for UC were obtained from the GEO database;intersection targets were identified by combining differentially expressed genes of the disease with the active components of the drug,and a protein-protein interaction (PPI) network was constructed using the STRING database; Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the intersection targets; based on the screened core components and core targets,molecular docking verification was conducted by Autodock Vina software to preliminarily verify the binding affinity between core components and targets. Results: A total of 83 active components of FHK were screened, corresponding to 1495 targets;GEO data revealed 973 differentially expressed genes for UC;there were 41 intersection targets being identified as potential targets for FHK in the treatment of UC. GO and KEGG results indicated that FHK primarily affected biological processes such as the response to lipopolysaccharides, response to bacterial molecules, activation of cytokines, and mediation of signaling pathways. These processes mainly occurred in membrane rafts and membrane microdomains and are closely related to tumor necrosis factor,lipid and atherosclerosis,and interleukin-17 signaling pathways. Molecular docking simulation results showed a high binding affinity between the active components of FHK and the core targets. Conclusion: The treatment of UC with FHK is achieved through multi-target, multipathway, and multi-process interactions. The primary action mechanism is likely focused on anti-inflammation and immune regulation.

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黄嘉恩,梁冠仪,何鉴洪,戴卫波,李乐愚.基于网络药理学和分子对接探讨番连化浊颗粒 治疗溃疡性结肠炎作用机制[J].新中医,2025,57(2):154-165

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  • 在线发布日期: 2025-02-05
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