基于网络药理学和分子对接技术探讨柴胡-黄芩治疗急性胰腺炎的作用机制※

Exploring the mechanism of action of Bupleurum and Scutellaria baicalensis in the treatment of acute pancreatitis based on network pharmacology and molecular docking technology

摘要:

目的 基于网络药理学和分子对接技术探讨“柴胡-黄芩”对急性胰腺炎的作用机制。方法 利用中药系统药理学数据库与分析平台，筛选出柴胡、黄芩的活性成分，借助SwissADME平台进一步筛选化合物，用SwissTarget Prediction数据库预测成分潜在作用靶点，应用Disgenet数据库、Gene Cards数据库、OMIM数据库获得急性胰腺炎相关靶点，将柴胡、黄芩活性化学成分相关靶点与急性胰腺炎相关靶点进行交集，并绘制韦恩图；针对两者交集靶点，利用STRING 12.0数据库及Cytoscape3.9.1软件构建蛋白质-蛋白质相互作用（PPI）网络；利用Metascape数据库对药物与疾病关键靶点进行基因本体论（Gene Ontology，GO）功能富集分析和京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes，KEGG）通路富集分析，通过Cytoscape3.9.1构建“中药-有效成分-作用靶点-疾病-通路”网络图，最后运用AutoDockTools1.5.7等软件进行分子对接验证，运用Pymol进行分子对接可视化。结果 共筛选出40个有效化学成分，487个药物作用靶点，疾病相关靶点1639个，药对中共180个作用靶点与急性胰腺炎存在交集关系，核心靶点为GAPDH、AKT1、BCL2、STAT3、CASP3等，GO分析结果主要涉及磷酸化的调节、磷酸盐代谢、细胞迁徙及运动等生物过程，KEGG主要富集在癌症通路、PI3K-Akt信号通路、Rap1信号通路、细胞凋亡、TNF信号通路等。柴胡和黄芩中去甲汉黄芩素、异鼠李素这2种活性成分与GAPDH、AKT1、BCL2、STAT3、CASP3均能够有效结合。结论 “柴胡-黄芩”可以通过多成分、多靶点、多维度、多通路治疗急性胰腺炎（起重要作用的成分为去甲汉黄芩素、异鼠李素等，靶点为GAPDH、AKT1、BCL2、STAT3、CASP3），可起到抗炎症反应、抗细胞凋亡、抗氧化应激反应等综合作用，这可为后续的研究提供理论基础及参考依据。

Abstract:

【】Objective To explore the mechanism of action of "Bupleurum-Scutellaria baicalensis" on acute pancreatitis based on network pharmacology and molecular docking technology. Method The traditional Chinese medicine systems pharmacology database and analysis platform were used to screen out the active ingredients of Bupleurum and Scutellaria baicalensis, and the compounds were further screened with the help of the SwissADME platform. Use the SwissTarget Prediction database to predict potential targets of ingredients, Apply Disgnet database, Gene Cards database, and OMIM database to obtain targets related to acute pancreatitis, Intersect the targets related to the active chemical components of Bupleurum and Scutellaria baicalensis with the targets related to acute pancreatitis, and draw a Venn diagram; Aiming at the intersection of the two targets, the STRING 12.0 database and Cytoscape3.9.1 software were used to construct a protein-protein interaction (PPI) network; Metascape database was used to conduct Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on key drug and disease targets. The "TCM-active ingredients-targets-disease-pathway" network diagram is constructed through Cytoscape3.9.1. Finally, software such as AutoDockTools1.5.7 was used for molecular docking verification, and Pymol was used for molecular docking visualization. Result A total of 41 effective chemical components, a total of 488 action targets, and 1,639 disease-related targets were screened out in "Bupleurum-Scutellaria baicalensis". There is an intersection relationship between the 180 targets of the drug and acute pancreatitis. The core targets are ABCB1, SIRT1, MMP2, CCND1, NR3C1, etc. The GO analysis results mainly involve biological processes such as the regulation of phosphorylation, phosphate metabolism, cell migration and movement, etc. KEGG is mainly enriched in cancer pathways, PI3K-Akt signaling pathway, Rap1 signaling pathway, apoptosis, TNF signaling pathway, etc. Five active ingredients in Bupleurum and Scutellaria baicalensis“Norwogonin、baicalein、isorhamnetin、5,7,4"-Trihydroxy-8-methoxyflavone、quercetin ” ,It can effectively combine with ABCB1, SIRT1, MMP2, CCND1, and NR3C1. In Conclusion “Bupleurum-Scutellaria baicalensis” can treat acute pancreatitis through multi-component, multi-dimensional, multi-dimensional, and multi-channel. The ingredients that play an important role are “Norwogonin、baicalein、isorhamnetin、5,7,4"-Trihydroxy-8-methoxyflavone、quercetin ”,The target is ABCB1, SIRT1, MMP2, CCND1, NR3C1, It plays a comprehensive role in anti-inflammatory response, anti-apoptosis, and anti-oxidative stress response. Provide theoretical basis and reference basis for subsequent research.