中国药学(英文版) ›› 2024, Vol. 33 ›› Issue (3): 258-271.DOI: 10.5246/jcps.2024.03.021
• 【研究论文】 • 上一篇
收稿日期:
2023-09-24
修回日期:
2023-10-27
接受日期:
2023-11-15
出版日期:
2024-03-31
发布日期:
2024-03-31
通讯作者:
喻斌
Siyu Wang1, Shuwei Zhou2, Bin Yu1,*()
Received:
2023-09-24
Revised:
2023-10-27
Accepted:
2023-11-15
Online:
2024-03-31
Published:
2024-03-31
Contact:
Bin Yu
Supported by:
摘要:
本研究旨在运用网络药理学分析方法与分子对接技术研究灭幽汤异病同治慢性萎缩性胃炎和胃溃疡的作用机制。运用TCMSP和BATMAN-TCM数据库筛选出灭幽汤的有效成分, Genecards、OMIM、Disgenet、Drugbank数据库筛选出慢性萎缩性胃炎和胃溃疡的相关靶点; 采用Cytoscape 3.9.1软件绘制"方剂-药物-活性成分-核心靶点-疾病"的网络拓扑图; 采用STRING数据库构建蛋白互作网络; 运用David数据库对核心靶点进行GO富集分析及KEGG通路分析; 采用AutoDock4软件进行分子对接预测药物与疾病靶点的结合性, 通过PyMOL 2.2软件实现对接结果可视化。结果得到灭幽汤有效成分73个, CAG相关靶点761个, GU相关靶点640个, 通过Venny图取交集后得到54个靶点, Cytoscape筛选后得核心靶点37个。分子对接结果显示, TP53、IL6等5种蛋白与木犀草素(luteolin)、金合欢素(acacetin)、柚皮素(naringenin)、黄芩苷(baicalein)、汉黄芩素(wogonin)有较好的结合活性; KEGG富集分析主要得到癌症通路、脂质与动脉粥样硬化、PI3K-Akt信号通路、MAPK信号通路、IL-17信号通路、AGE-RAGE信号通路等。研究表明, 灭幽汤异病同治慢性萎缩性胃炎和胃溃疡具有多成分、多靶点及多通路的特性, 其主要成分与活性分子靶点结合, 通过调控癌症、脂质与动脉粥样硬化等信号通路实现"同治"CAG和GU的目的。为传统中医药的"异病同治"理论提供了现代医学证据, 并且为今后的新药研发与实验设计指明了方向。
Supporting:
王思宇, 周淑伟, 喻斌. 基于网络药理学-分子对接探析灭幽汤"异病同治"慢性萎缩性胃炎和胃溃疡的作用机制[J]. 中国药学(英文版), 2024, 33(3): 258-271.
Siyu Wang, Shuwei Zhou, Bin Yu. Exploring the mechanism of Mie-you decoction "homotherapy for heteropathy" to chronic atrophic gastritis and gastric ulcer using network pharmacology-molecular docking[J]. Journal of Chinese Pharmaceutical Sciences, 2024, 33(3): 258-271.
Figure 1. Venny diagram of the treatment of CAG and GU targets with Mie-you decoction. Note: blue represents the number of targets for CAG, yellow represents the number of targets for GU, green represents the number of targets for MYT, and the middle part represents the intersection targets of the three.
Figure 2. The "drug-disease" core target protein interaction network of MYT in the treatment of CAG and GU. Note: Nodes represent proteins (The colors from yellow to blue and the size from small to large represent the degree of each protein). Edge represents protein-protein association (The lines from thin to thick and the color from light to dark reflect the betweenness value between proteins).
Figure 3. Drug-ingredients-target-disease network. Note: the red hexagon nodes represent CAG and GU. The blue diamond nodes represent the target proteins. The orange oval nodes represent the bioactive ingredients of herbs. The light green triangle nodes represent herbs of MYT, including Scutellariae Radix (HQ), Citrus Reticulata (CP), Citri Reticulatae Pericarpium Viride (QP), Bletilla Striata (BJ), PanaxNotoginseng (SQ) and Taraxaci Herba (PGY). The green rectangular node represents MYT. Edges represent the interactions between goals and targets.
Figure 6. Partial molecular docking results of main bioactive ingredients of Mie-you decoction. Note: (A) AKT1-baicalein; (B) IL6-luteolin; (C) PTGS2-acacetin; (D) TP53-naringenin; (E) VEGFA-wogonin.
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