基于网络药理学探讨黄芪治疗病毒性胰腺炎的疗效及机制
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1.中国医学科学院/北京协和医学院;2.医学生物学研究所;3.云南大学生命科学学院

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中国医学科学院医学与健康科技创新工程(2021-I2M-1-024 );云南省基础研究专项面上项目(202401CF070048)


Network Pharmacology Analysis of Efficacy and Mechanism of Astragalus in the Treatment of Viral Pancreatitis
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Affiliation:

1.Institute of Medical Biology,Chinese Academy of Medical Sciences &2.amp;3.Peking Union Medical College;4.College of Life Sciences, Yunnan university

Fund Project:

Medical and Health Science and Technology Innovation Program, Chinese Academy of Medical Sciences(2021-I2M-1-024 );Yunnan Fundamental Research Projects (202401CF070048)

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    摘要:

    目的 基于网络药理学与细胞实验探讨黄芪治疗病毒性胰腺炎疗效及可能的作用机制。方法 检索TCMSP数据库中黄芪的药物靶点,结合GeneCards数据库中病毒性胰腺炎的疾病靶点,两者取交集获得黄芪治疗病毒性胰腺炎的靶点基因。基于DAVID数据库完成治疗靶点的基因本体(GO)功能富集分析和京都基因与基因组数据库(KEGG)信号通路富集分析。治疗靶点经STRING数据库与Cytoscape 3.10.2软件分析其相互作用关系并筛选核心治疗靶点,采用PyMOL 3.0 与AutoDock Tolls 1.5.7软件完成最主要有效治疗成分与核心靶点的分子对接,利用柯萨奇病毒B组3型(Coxsackievirus B3, CVB3)构建病毒性胰腺炎细胞模型,并对上述核心靶点进行验证。结果 经筛选获得78个治疗靶点,富集分析结果显示,黄芪治疗病毒性胰腺炎可能涉及的信号通路有癌症通路、PI3K-AKT信号通路、脂质与动脉粥样硬化等,此外,AKT1、 TP53、HIF1A、CASP3、IL-6、MMP9等基因可能是黄芪治疗病毒性胰腺炎的核心靶点,细胞实验结果表明,模型组淀粉酶(amylase, AMY)表达水平显著升高,黄芪组相较于模型组AMY、AKT1、 TP53、HIF1A、CASP3、IL-6、MMP9表达水平显著下降。 结论 黄芪注射液能有效治疗病毒性胰腺炎,并可能通过降低AKT1、 TP53、HIF1A、CASP3、IL-6、MMP9表达水平发挥治疗作用。

    Abstract:

    Objective This study aims to explore the efficacy and underlying mechanism of Astragalus in the treatment of Viral Pancreatitis using network pharmacology, and subsequently confirm the efficacy and mechanism in cell experiments. Methods Astragalus and Viral Pancreatitis targets were obtained in TCMSP and Gene Cards database, then combining the two results to obtain intersection targets. GO functional enrichment analysis and KEGG signaling pathway enrichment analysis of therapeutic targets were conducted based on DAVID database. The interaction between the therapeutic targets was analyzed by STRING database and Cytoscape 3.10.2, and the core therapeutic targets were screened. PyMOL 3.0 and AutoDock Tolls 1.5.7 were used to complete the molecular docking between the most effective therapeutic components and the core targets. The CVB3 virus was used to construct a viral pancreatitis cell model, and the above core targets were verified. Results 78 therapeutic targets were obtained. The results of enrichment analysis showed that the possible signaling pathways were cancer pathway, lipid and atherosclerosis, PI3K-AKT signaling pathway, etc. In addition, AKT1, TP53, HIF1 A, CASP3, IL-6, MMP9 may be the core targets. The results of cell experiments showed that the expression level of AMY in the model group was significantly increased. The expression levels of AMY, AKT1, TP53, HIF1 A, CASP3, IL-6 and MMP9 in the Astragalus Injection group were significantly decreased compared with the model group. Conclusion Astragalus injection can effectively treat viral pancreatitis, and may play a therapeutic role by reducing the expression levels of AKT1, TP53, HIF1 A, CASP3, IL-6 and MMP9.

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  • 收稿日期:2024-08-21
  • 最后修改日期:2025-02-25
  • 录用日期:2025-05-06
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