基于网络药理学的黄芪建中汤治疗慢性萎缩性胃炎作用机制研究

Mechanism of Huangqi Jianzhong Decoction in treating chronic atrophic gastritis based on network pharmacology

目的筛选黄芪建中汤中治疗慢性萎缩性胃炎的主要活性成分,预测活性成分的作用靶点,建立单味药-活性成分-作用靶点网络,进一步探讨黄芪建中汤治疗慢性萎缩性胃炎的潜在作用机制。方法采用中药系统药理学技术平台(TCMSP)中的药动学参数[口服利用度(OB)和药物相似性(DL)]筛选黄芪建中汤的潜在活性成分,整合靶点预测网站服务器(STPD)与人类基因数据库(Genecard)、人类孟德尔遗传数据库(OMIM)预测和筛选其治疗慢性萎缩性胃炎的作用靶点,借助Cytoscape构建"单味药-活性成分-作用靶点"网络。通过Systems Dock Web Site对4个主要活性成分与作用靶点进行分子对接验证。采用String数据库与Cytoscape软件绘制蛋白质相互作用网络,并利用Dis Ge NET数据库对作用靶点类型进行归属。采用DAVID数据库对黄芪建中汤作用靶点进行生物功能及代谢通路分析。结果通过OB和DL参数筛选得到118个潜在活性成分,共涉及16个作用靶点,与疾病靶点有关的活性成分为52个,主要通过调控癌症通路、病灶黏连、精氨酸和脯氨酸代谢、血管内皮生长因子(VEGF)信号转导与神经营养因子信号通路等发挥对慢性萎缩性胃炎的治疗作用。结论黄芪建中汤对慢性萎缩性胃炎的治疗作用体现了中药多成分-多靶点-多途径的特点,为阐释其治疗慢性萎缩性胃炎的作用机制与物质基础提供了科学依据。

Objective To predict the active ingredients and their potential targets of Huangqi Jianzhong Decoction（HQJZ） against chronic atrophic gastritis（CAG） based on the ＂single drug-active ingredient-action targets＂ network. Methods Using pharmacokinetic parameters [oral bioavailability（OB） and drug likeness（DL）] of traditional Chinese medicine system pharmacology platform（TCMSP） to screen the active ingredient of HQJZ, and then integrating target prediction database（STPD）, human gene database（Genecard）, and Online Mendelian Inheritance in Man（OMIM） to predict and screen its target genes for the treatment of CAG, and using Cytoscape software to construct the network of ＂single drug-active ingredient-action targets＂. The molecular docking of those main active ingredient and action targets were confirmed through Systems Dock Web Site. String database and Cytoscape software were used to draw the protein interaction network, and Dis Ge NET database was used to assign their target type. Finally the biological function and metabolic pathway of these targets were analyzed by DAVID database. Results A total of 118 potential active ingredients were screened based on their OB and DL parameters, and 16 CAG-related genes were involved, 52 active ingredients were related to disease target, which mainly involved in the regulations of cancer pathway, focal adhesion, arginine and proline metabolism, vascular endothelial growth factor signal transduction and neurotrophic factor signaling pathway in the treatment of chronic atrophic gastritis. Conclusion The therapeutic mechanism of HQJZ reflects the characteristics of multi-component, multi-target, and multi-pathway of traditional Chinese medicines, which provides a scientific basis for further explaining the action mechanism and the material basis of HQJZ against CAG.