摘要
目的:基于网络药理学、分子对接技术和体外实验,探讨厚朴枳实大黄治疗糖尿病的潜在作用机制。方法:借助中药系统药理学数据库与分析平台(TCMSP),获取厚朴枳实大黄的主要化学成分及对应靶标基因,通过人类基因数据库(GeneCards)获取糖尿病相关疾病基因。将药物靶标基因与疾病相关基因进行映射取交集,得到厚朴枳实大黄预防和治疗糖尿病的潜在作用靶点。随后,利用在线工具进行基因本体(GO)分析和京都基因及基因组百科全书(KEGG)通路富集分析,并获得蛋白与蛋白相互作用网络(PPI),挖掘出其治疗糖尿病的潜在信号通路。利用Cytoscape软件构建中药化合物-靶点-信号通路网络,从而进一步发掘药物治疗糖尿病的潜在化学成分及核心靶点。并采用AutoDock Vina等软件进一步确证潜在活性成分与核心靶点的结合能力。采用DPPH自由基清除实验评价厚朴枳实大黄的抗氧化应激效果,以及LPS诱导的巨噬细胞炎症模型检测其抗炎效果。结果:厚朴、枳实、大黄作用于糖尿病的潜在有效成分分别有10个、2个、19个,对应的关键靶点分别有61个、23个、118个。GO分析结果显示,厚朴枳实大黄治疗糖尿病潜在基因的生物功能主要涉及信号转导、磷酸化调控、蛋白磷酸化、脂多糖反应、氧化应激反应、炎症反应调控等。KEGG通路富集结果显示,厚朴枳实大黄治疗糖尿病潜在基因主要涉及PI3K-Akt信号通路、胰岛素抵抗信号通路、2型糖尿病信号通路等胰岛素相关通路,以及TNF信号通路、p53信号通路、MAPK信号通路、NF-kappa B信号通路等炎症相关通路。体外实验结果表明,厚朴枳实大黄能够显著清除DPPH自由基,并抑制炎症因子释放。结论:厚朴枳实大黄治疗糖尿病是多成分、多靶点、多通路的复杂过程,可能通过改善氧化应激和炎症异常等发挥治疗糖尿病的作用。
Objective:This study aims to investigate the therapeutic mechanisms of action of Cortex Magnoliae Officinalis,Fructus Aurantii Immaturus and Radix et Rhizoma Rhei in the prevention and treatment of diabetes by using network pharmacology,molecular docking and in vitro experiment.Methods:TCMSP platform was employed to obtain the chemical compounds,and corresponding targets of Cortex Magnoliae Officinalis-Fructus Aurantii Immaturus-Radix et Rhizoma Rhei,while the diabetes-related disease genes were extracted from the Human Gene Database(GeneCards).The drug target genes and disease-related genes are mapped and intersected,and the potential targets for preventing and treating diabetes are obtained.Then,the online tools were used for gene ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis,and the protein-protein interaction network(PPI)was obtained,and its potential signal pathway for treating diabetes was excavated.The compound-target-signal pathway network of traditional Chinese medicine was constructed by Cytoscape software,so as to further explore the potential chemical components and core targets of drugs in treating diabetes.AutoDock Vina and other software were used to further confirm the binding ability of potential active ingredients with core targets.DPPH free radical scavenging experiment was used to evaluate the anti-oxidative stress effect of Magnolia officinalis and Rhubarb,and LPS-induced macrophage inflammation model was used to detect its anti-inflammatory effect.Results:The effective components of Cortex Magnoliae Officinalis,Fructus Aurantii Immaturus,Radix et Rhizoma Rhei in the treatment of diabetes included 10,2,19 with 61,23,118 corresponding targets,respectively.GO analysis showed that the potential genes targeted by these compounds for treating diabetes were mainly involved in signal transduction,regulation of phosphorylation,regulation of protein phosphorylation,response to lipopolysaccharide,response to oxidative stress,etc.KEGG pathway enrichment analysis suggested that the pathways involved mainly included PI3K-Akt signaling pathway,TNF signaling pathway,p53signaling pathway,insulin resistance,MAPK signaling pathway,type II diabetes mellitus,NF-kappa B signaling pathway,etc.The results of in vitro experiment indicated that this formula possessed antioxidant effect,and significantly prevented the release of inflammatory factors.Conclusion:Network pharmacology results suggests that the herbal formula of Cortex Magnoliae Officinalis,Fructus Aurantii Immaturus,Radix et Rhizoma Rhei shows great potential for the treatment of diabetes mellitus via multi-components,multi-targets and multipathways.Multiple signal pathways,such as oxidative stress and inflammatory response related signal pathways are involved in the treatment of diabetes mellitus by this formula.
作者
陈登科
金恩佑
江国安
贺恰仁
马丽
杨乐乐
张俊
CHEN Dengke;JIN Enyou;JIANG Guoan(Faculty of Chinese Medicine,Macao University of Science and Technology,Macao 999078,China;Famous Doctor's Studio of Chen Dengke in Shaoguan Hospital of Traditional Chinese Medicine,Shaoguan 512000,China)
出处
《四川中医》
2025年第2期82-91,共10页
Journal of Sichuan of Traditional Chinese Medicine
基金
国家自然科学基金项目(编号:82204588)。
关键词
厚朴
枳实
大黄
糖尿病
作用机制
网络药理学
Cortex Magnoliae Officinalis
Fructus Aurantii Immaturus
Radix et Rhizoma Rhei
Diabetes mellitus
Mechanism of action
Network pharmacology
