基于网络药理学和分子对接研究调胃安肠方治疗脓毒血症作用机制
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R285

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广东省中医药局科研项目(20221468)


Exploring Mechanism of Action of Tiaowei Anchang Prescription for Sepsis Based on Network Pharmacology and Molecular Docking
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    摘要:

    目的:运用网络药理学、分子对接以及分子动力学模拟研究调胃安肠方治疗脓毒血症的作用机制。 方法: 通过中药系统药理学数据库(TCMSP) 预测调胃安肠方的潜在靶点, 使用基因信息数据 库(GeneCards)、在线人类孟德尔遗传数据库(OMIM)、药物靶标数据库(TTD) 和药物数据库(Drugbank) 检索与脓毒血症相关的靶点。借助Cytoscape 3.9.1软件构建“药物-成分-靶点”网络,同时利用STRING数据 库构建蛋白质互作(PPI) 网络。采用DAVID 数据库进行基因本体(GO) 功能和京都基因及基因组百科全 书(KEGG) 通路富集分析;通过AutoDock Vina和PyMOL进行有效成分与重要靶点的分子对接,并用Gromacs 2022.2软件对蛋白激酶B(AKT1) 和β-谷甾醇进行分子动力学模拟。结果:共筛选出调胃安肠方224种有效 成分和279个潜在靶点,与脓毒血症相关的靶点共3 718个,有效成分与疾病相关的共同靶点为171个,主要 涉及炎症反应等生物过程,以及高级糖基化终末产物-受体(AGE-RAGE) 等信号通路对脓毒血症的影响。分 子对接结果显示,调胃安肠方5种活性成分(槲皮素、山奈酚、β-谷甾醇、柚皮素、异鼠李素) 与筛选出的 靶蛋白度值(degree) 前10 个关键靶点(c-Jun 蛋白、p53 蛋白、白细胞介素-6、信号转导和转录激活因子 3、蛋白激酶B、人雌激素受体1、肿瘤坏死因子、核因子-κB p65亚基、丝裂原活化蛋白激酶3、丝裂原活化 蛋白激酶1) 均具有较好的结合活性。分子动力学模拟提示AKT1和β-谷甾醇的结合稳定且紧密。结论:调胃 安肠方可通过多靶点、多途径对脓毒血症起治疗作用

    Abstract:

    Abstract: Objective: To explore the mechanism of action of Tiaowei Anchang Prescription in the treatment of sepsis using network pharmacology, molecular docking and molecular dynamics simulation. Methods: The potential targets of Tiaowei Anchang Prescription were predicted by TCMSP database. Sepsis-related disease targets were searched using GeneCards, OMlM, TTD and Drugbank. Cytoscape3.9.1 software was used to construct the "drug- component-target" network, and the STRlNG database was used to construct the protein-protein interaction (PPI) network. DAVlD database was used for GO functional enrichment and KEGG pathway richment analysis of genes. AutoDock Vina and PyMOL software were used to dock the active ingredients with the molecules of key targets. Gromacs2022.2 software was used to simulate the molecular dynamics of AKT1 and β-sitosterol. Results: A total of 224 active ingredients and 279 potential targets, 3 718 disease-related targets, and 171 disease-related common targets were obtained through screening, which mainly involved biological processes such as inflammatory response, and the advanced glycation end product (AGE)-receptor for AGE (RAGE) signaling pathway had an impact on sepsis. The results of molecular docking showed that five active ingredients (quercetin, kaempferol, β -sitosterol, naringenin, and isorhamnetin) of Tiaowei Anchang Prescription all had good binding activities with the top 10 key targets (c-Jun protein,p53 protein,interleukin-6,signal transducer and activator of transcription 3,protein kinase B, estrogen receptor α, tumor necrosis factor, NF- κB p65 subunit, mitogen-activated protein kinase 3, and mitogen-activated protein kinase 1) with the degree values of the screened target proteins. Molecular dynamics simulations showed that the binding of AKT1 and β-sitosterol was stable and tight. Conclusion: Tiaowei Anchang Prescription can play a therapeutic role in sepsis through multiple targets and multiple pathways.

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范玲彬,黄建略,曾凡鹏.基于网络药理学和分子对接研究调胃安肠方治疗脓毒血症作用机制[J].新中医,2025,57(13):173-181

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  • 在线发布日期: 2025-07-14
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