摘要
目的:基于网络药理学和分子对接技术探究半夏泻心汤治疗糖尿病认知功能障碍(diabetes-associated cognitive dysfunction,DCD)的作用机制。方法:使用中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)、PubChem等数据库筛选半夏泻心汤主要活性成分,结合SuperPred靶点预测工具、BATMAN、UniProt数据库预测活性成分可能的作用靶点;通过在线人类孟德尔遗传数据库(online mendelian inheritance in man,OMIM)、人类基因数据库(the human gene database,GeneCards)、TTD、DrugBank及PharmGkb数据库搜索并建立DCD疾病靶点信息数据集,利用STITCH、STRING数据库以及Cytoscape 3.8.1软件构建成分靶点与疾病靶点蛋白-蛋白互作(protein-protein interactions,PPI)网络;将核心靶点导入DAVID 6.8数据库,进行基因本体论(gene ontology,GO)功能富集与京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路分析;通过Open Babel 2.3.2软件及Protein Data Bank数据库获得受体蛋白,利用PYMOL 2.3.4、AutoDock Tools及Vina 1.1.2等软件对受体蛋白与配体小分子分别进行分子对接。运用高效液相色谱方法分析含有汉黄芩素、小檗碱、黄芩素、甘草苷的混标样品及含药血清。结果:筛选出190个半夏泻心汤潜在活性成分、281个化合物靶点及1490个DCD相关靶点;拓扑分析得到34个核心靶点;GO功能富集分析和KEGG通路分析得到358个生物过程条目及92条通路;分子对接发现,配体小分子均稳定地位于对接口袋内,其中,原阿片碱与活性位点附近的Tyr-634、Tyr-651、Lys-652氨基酸形成氢键结合到SIRT1,其对接得分值最佳;高效液相色谱分析发现,含药血清中可能含有汉黄芩素、小檗碱、黄芩素、甘草苷等药物代谢后的成分。结论:半夏泻心汤治疗DCD具有多通路、多靶点等作用,其主要通过FoxO、HIF-1、MAPK、雌激素、TNF、癌症和Toll样受体等信号通路发挥抑制细胞凋亡、抗炎、抗氧化,调节自噬及突触可塑性等作用。
Objective:To survey the mechanism of Banxia Xiexin decoction in the treatment of diabetesassociated cognitive dysfunction(DACD)based on network pharmacology and molecular docking.Methods:The main active ingredients of Banxia Xiexin decoction were screened from TCMSP and PubChem,and the targets of action of the active ingredients were predicted using SuperPred target prediction tool,BATMAN and UniProt database;the data and information set of DACD-related targets were searched via OMIM,GeneCards,TTD,DrugBank and PharmGkb,and established,STITCH,STRING and Cytoscape 3.8.1 software were utilized to build PPI of component targets and disease targets;GO and KEGG pathway analysis were conducted after importing core targets into DAVID 6.8 database.Receptor proteins were obtained from Open Babel 2.3.2 and Protein Data Bank,PYMOL 2.3.4,AutoDock Tools and Vina 1.1.2 were adopted to carry out molecular docking of receptor proteins and ligand small molecules separately.HPLC was applied to analyze the mixed samples and the medicated serum contained wogonin,berberine,baicalin and glycyrrhizin.Results:All 190 potential active ingredients of the decoction,281 targets of the compounds and 1490 DACD-related targets were screened out;topology analysis has yielded 34 core targets;358 biological process entries and 92 pathways were obtained by GO and KEGG pathway analysis;molecular docking revealed that ligand molecules were stably located in the docking pocket.Among them,the original opioid alkaloid formed hydrogen bonds with Tyr-634,Tyr-651 and Lys-652 amino acids near the active site to bind to SIRT1,and its docking score was the best;HPLC displayed that the medicated serum might contain the ingredients after the metabolism of wogonin,berberine,baicalin and glycyrrhizin.Conclusion:Banxia Xiexin decoction could treat DACD via multiple targets and multiple pathways,and it mainly inhibits cellular apoptosis,anti-inflammatory and antioxidant effects,adjusting autophagy and synaptic plasticity via FoxO,HIF-1,MAPK,estrogen,TNF,cancer and Toll-like receptors.
作者
盛沛
王旭
石崯力
SHENG Pei;WANG Xu;SHI Yinli(The First Clinical Medical College of Nanjing University of Chinese Medicine,Nanjing 210029,China;Affiliated Hospital of Nanjing University of TCM,Nanjing 210029,China)
出处
《西部中医药》
2026年第2期56-67,共12页
Western Journal of Traditional Chinese Medicine
基金
国家自然科学基金(81973796)
江苏省研究生创新课题项目(SJCX21_0725)。
关键词
糖尿病认知功能障碍
半夏泻心汤
网络药理学
分子对接
高效液相色谱
diabetes-associated cognitive dysfunction
Banxia Xiexin decoction
network pharmacology
molecular docking
HPLC
