摘要
目的:整合网络药理学和体外实验阐释生姜-乌梅药对调控肠动力的潜在机制。方法:从不同数据库检索生姜-乌梅药对的成分及对应靶点,利用GeneCards和OMIM数据库收集急性腹泻的疾病基因;通过Cytoscape 3.10.2软件构建“药物-有效成分-靶点-疾病”网络图;将获取的“药物-疾病”交集靶点导入STRING数据库构建PPI网络图;利用DAVID数据库对复合靶点进行GO功能富集分析。基于富集分析结果,使用体外细胞实验方法对药物调控肠动力的作用机制进行验证。结果:共筛选出有效成分36个,有效成分作用靶点176个;富集分析结果显示该药对调控肠动力的作用机制与蛋白质磷酸化、细胞凋亡、线粒体、ATP等密切相关;通过细胞实验,该富集分析结果得到了进一步验证。结论:该研究通过网络药理学揭示了生姜-乌梅药对通过多途径、多成分和多靶点发挥对肠动力的调控作用;体外实验明确其作用机制为该药对可增加细胞内ROS含量,降低线粒体膜电位及ATP含量,促进细胞自噬,诱导细胞凋亡,降低细胞数量来调控肠动力,改善肠蠕动亢进。
OBJECTIVE To explain the potential mechanism of Ginger-Chinese plums drug pair on regulating intestinal motility by integrating network pharmacology and in vitro experiments.METHODS The drug components and corresponding targets of ginger-Chinese plums drug pair were searched from different databases,and the disease genes of acute diarrhea were col-lected using GeneCards and Online Mendelian Inheritance in Man(OMIM)databases.The"drug-active component-target-disease"network was constructed by Cytoscape 3.10.2 software.The obtained intersection targets of"drug-disease"were imported into the Search Tool for the Retrieval of Interacting Genes(STRING)database to construct a protein-protein interaction(PPI)network.Gene Ontology(GO)functional enrichment analysis of the complex target sites were performed using the Data-base for Annotation,Visualization and Integrated Discovery(DAVID).Based on the results of enrichment analysis,the mecha-nism of regulating intestinal motility was validated using in vitro experiments.RESULTS A total of 36 active ingredients and 176 targets of active ingredients were selected.The enrichment analysis results showed that the regulatory effect of the Ginger-Chinese plums drug pair on intestinal motility was closely related to protein phosphorylation,apoptosis,mitochondria,and adenos-ine triphosphate(ATP).In vitro experiments further validated the enrichment analysis results.CONCLUSION Network phar-macology reveals that ginger-Chinese plums drug pair drug pair exerts its therapeutic effect on regulating intestinal motility through multiple pathways,multiple components and multiple targets.In vitro experiments confirm that the mechanism of action is to increase intracellular reactive oxygen species(ROS)content,decrease mitochondrial membrane potential and ATP content,pro-mote autophagy,induce apoptosis,reduce cell number to regulate intestinal motility and improve intestinal hyperperistalsis.
作者
刘燕
玄静
姜秋
颜培正
王树增
LIU Yan;XUAN Jing;JIANG Qiu;YAN Peizheng;WANG Shuzeng(School of Pharmacy,Shandong University of Traditional Chinese Medicine,Shandong Jinan 250355,China;School of Forestry Engineering,Shandong Agriculture and Engineering University,Shandong Jinan 250000,China;Department of Traditional Chinese Medicine,Changqing District People's Hospital,Shandong Jinan 250399,China)
出处
《中国医院药学杂志》
北大核心
2025年第21期2451-2457,共7页
Chinese Journal of Hospital Pharmacy
基金
山东中医药大学科学研究基金项目(编号:KYZK2024Q28)
山东省中医药科技项目(编号:Q-2022057)。
关键词
生姜-乌梅
肠动力
作用机制
线粒体
细胞自噬
ginger-Chinese plums
intestinal motility
mechanism of action
mitochondria
autophagy
