摘要
目的:利用网络药理学技术和分子对接研究健脾益肾方治疗慢性肾脏病的作用机制。方法:通过中药系统药理学数据库和分析平台(TCMSP)及中医药整合药理学研究平台(Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine,TCMIP)v2.0收集健脾益肾方中八味中药的主要活性成分,通过TCMSP及Swiss Target Prediction数据库查询活性成分的靶点信息;从人类基因数据库(GeneCards)、《人类孟德尔遗传》数据库(OMIM)、Drugbank、疗效药靶数据库(TTD)中获取慢性肾脏病的相关靶标;取活性成分靶标与疾病靶标的交集,根据拓扑特征值筛选健脾益肾方治疗慢性肾脏病的关键靶标;将关键靶标进行GO功能分析和KEGG信号通路分析,并采用Cytoscape 3.7.0构建“中药-关键活性成分-核心靶标-信号通路”,并筛选其核心网络。结果:健脾益肾方中槲皮素、山柰酚、木犀草素等为其发挥作用的核心活性成分,雌激素受体1(ESR1)、雄激素受体(AR)、过氧化物酶体增殖物激活受体γ(PPARG)、前列腺素-内过氧化物合酶1(PTGS1)、核受体共激活剂2(NCOA2)等为其关键靶标,可能通过调控对药物的反应、凋亡过程的负调控、老化等生物学过程,作用于胞质溶胶、质膜、核质等细胞组分,影响酶结合、碳酸盐脱水酶活性、药物结合等分子功能,通过改善组织局部血供,促进血管生成,改善氧化应激状态,调节慢性炎症,改善甲状腺激素水平,改善慢性肾脏病的胰岛素抵抗,抑制慢性肾脏病细胞凋亡等信号通路发挥治疗慢性肾脏病的作用。分子对接结果显示,核心活性成分与核心靶标之间结合作用良好。结论:该研究基于网络药理学和分子对接的方法筛选健脾益肾方治疗慢性肾脏病的核心活性成分及其调控的关键靶标、信号通路,揭示了健脾益肾方通过多成分、多靶点、多通路改善慢性肾脏病的作用,为后续研究提供了丰富的信息和理论依据。
Objective:To study the mechanism of Jianpi Yishen Recipe in the treatment of chronic kidney disease by network pharmacology and molecular docking.Methods The active ingredients information of the eight traditional Chinese medicines in Jianpi Yishen Recipe was collected through the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP)and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine(TCMIP)v2.0.The target information was collected from TCMSP and Swiss Target Prediction.Chronic kidney disease-related gene targets were obtained from the Human Gene Database(GeneCards),"Human Mendelian Inheritance"database(OMIM),Drugbank,and therapeutic drug target database(TTD).The intersection of active ingredient targets and disease targets were screened as the key targets of Jianpi Yishen Recipe in the treatment of chronic kidney disease based on topological feature values.GO function analysis and KEGG signal pathway analysis were performed on key targets,and Cytoscape 3.7.0 was used to construct a network of"traditional Chinese medicine-key active ingredients-core target-signal pathway"and screen its core network.Results:Quercetin,kaempferol,luteolin,and other active ingredients were core active ingredients of Jianpi Yishen Recipe in the treatment of chronic kidney disease.Estrogen receptor 1(ESR1),androgen receptor(AR),peroxisome proliferator activated receptor gamma(PPARγ),prostaglandin-endoperoxid synthase 1(PTGS1),nuclear receptor co-activator 2(NCOA2),and other targets were the key targets.Jianpi Yishen Recipe might regulate the response to drugs;negatively regulate apoptosis process,aging,and other biological processes;act on cellular components such as cytosol,plasma membrane,nucleoplasm;affect molecular functions,such as enzyme binding,carbonate dehydratase activity,drug binding,etc..In addition,Jianpi Yishen Recipe might treat chronic kidney disease by improving tissue local blood supply,promoting angiogenesis,improving oxidative stress,regulating chronic inflammation,improving thyroid hormone levels and insulin resistance in chronic kidney disease,inhibiting the apoptosis.Conclusion:The results of molecular docking showed an excellent binding effect between the core active ingredients and the core targets.Based on the network pharmacology method and molecular docking,this study screened the critical active ingredients of Jianpi Yishen Recipe in the treatment of chronic kidney disease and the key targets and signal pathways for its regulation,revealing that Jianpi Yishen Recipe could improve chronic kidney disease through multiple components,multiple targets and multiple pathways.The role of kidney disease provided a wealth of information and a theoretical basis for follow-up research.
作者
索娟
赵元
卢锦华
陈剑平
Suo Juan;Zhan Yuan;Lu Jinhua;Chen Jianping(Shenzhen Traditional Chinese Medicine Hospital,the Fourth Clinical College of Guangzhou University of Chinese Medicine,Guangdong 518033;Shenzhen Nanyue Pharmaceutical Co Ltd,Guangdong 518110)
出处
《天津药学》
2021年第5期34-42,共9页
Tianjin Pharmacy
基金
国家自然科学基金项目(No.81804052,82004248)
广东省中医药局项目(No.20201320)
深圳市科技计划项目(No.JSGG20191129102216637)。
关键词
健脾益肾方
慢性肾脏病
网络药理学
核心活性成分
分子对接
Jianpi Yishen Recipe
chronic kidney disease
network pharmacology
key active ingredients
molecular docking
