摘要
目的:通过网络药理学和分子对接技术预测大黄蛰虫丸(DHZCP)治疗糖尿病肾病(DKD)的潜在靶点及机制。方法:运用中药系统药理学数据库和分析平台(TCMSP)以及中国知网、万方数据库、PubMed数据库等搜集DHZCP各药活性成分,利用PubChem、Swiss Target Prediction数据库获取各成分靶点,利用GeneCards、DisGeNet、OMIM及TTD数据库筛选DKD相关靶基因,取交集获得潜在治疗靶点。通过STRING平台构建蛋白-蛋白互作网络,并通过Cytoscape 3.8.2软件构建“药物-活性成分-靶点-疾病”网络图,筛选核心活性成分和靶点。利用David平台进行KEGG通路与GO功能富集分析。最后利用Autodock vina V1.2.0软件进行分子对接。结果:DHZCP各成分靶点1 102个,DKD相关靶点基因4 001个,DHZCP治疗DKD的潜在靶点641个。DHZCP治疗DKD的核心活性成分为甘草黄酮、甘草查尔酮B、β-谷甾醇、谷甾醇、山奈酚、豆甾醇,核心靶点为肿瘤蛋白P53(TP53)、非受体酪氨酸激酶(SRC)、AKT丝氨酸/苏氨酸激酶1(AKT1)、磷脂酰肌醇4,5-二磷酸3-激酶催化亚基α(PIK3CA)、磷酸肌醇3激酶调节亚基1(PIK3R1)、信号转导和转录激活因子3(STAT3)。GO功能富集显示,DHZCP治疗DKD涉及蛋白质磷酸化、对外源性刺激的反应等;KEGG通路富集显示关键信号通路包括血脂与动脉粥样硬化、糖尿症并发症中的糖基化终末产物-糖基化终末产物受体信号通路等。分子对接显示核心活性成分和核心靶点均结合稳定。结论:DHZCP可能通过甘草黄酮、甘草查尔酮B、β-谷甾醇、谷甾醇、山奈酚、豆甾醇等活性成分,作用于TP53、SRC、AKT1、PIK3CA、PIK3R1、STAT3等靶点及多条通路,发挥治疗DKD的作用。
Aim:To analyze the potential targets and therapeutic mechanism of Dahuang Zhechong pill(DHZCP)in the treatment of diabetic kidney disease(DKD)through network pharmacology and molecular docking technology.Methods:The active components of each drug of DHZCP were collected using the TCMSP database and literature data.The targets of each component were obtained using the PubChem and Swiss Target Prediction databases,the target genes of DKD were screened using the GeneCards,DisGeNet,OMIM and TTD databases,take the intersection to obtain the therapeutic targets.The protein-protein interaction network was constructed through the STRING platform,and the"drug-active ingredient-target-disease"network graph was constructed through Cytoscape 3.8.2 software to screen the core targets and components.The functional enrichment analysis of KEGG and GO was conducted using the David platform.Finally,molecular docking was carried out using the Autodock vina V1.2.0 software.Results:There were 1102 DHZCP targets and 4001 DKD targets,and 641 effective targets of DHZCP in the treatment of DKD.The core ingredients were glycyrrhiza flavonoids,glycyrrhiza chalcone B,β-sitosterol,sitosterol,kaempferol,stigmasterol.The core targets were tumor protein P53(TP53),non receptor tyrosine kinase(SRC),AKT serine/threonine kinase 1(AKT1),phosphatidylinositol 4,5-diphosphate 3-kinase catalytic subunit alpha(PIK3CA),phosphoinositol 3-kinase regulatory subunit 1(PIK3R1),and signal transduction and transcription activator 3(STAT3).The functional enrichment of GO showed that DHZCP in the treatment of DKD involved protein phosphorylation,exogenous stimulation,etc.KEGG showed that the key signaling pathways included those of lipid and atherosclerosis,AGE-RAGE,etc.Molecular docking showed that both the core targets and the core active ingredients were stably bound.Conclusion:DHZCP may exert its effects for treating DKD through active components such as glycyrrhiza flavonoids,glycyrrhiza chalcone B,β-sitosterol,etc.and acting on TP53,SRC,AKT1,PIK3CA,PIK3R1,STATE3,and multiple pathways.
作者
窦雪伟
崔文飞
董浩洋
申雨澎
王瑾瑾
闫国立
DOU Xuewei;CUI Wenfei;DONG Haoyang;SHEN Yupeng;WANG Jinjin;YAN Guoli(Teaching and Research Center of Public Health and Preventive Medicine,School of Medicine,Henan University of Chinese Medicine,Zhengzhou 450046)
出处
《郑州大学学报(医学版)》
北大核心
2025年第3期342-348,共7页
Journal of Zhengzhou University(Medical Sciences)
基金
国家自然科学基金项目(82104748)
河南省科技攻关计划项目(242102311282)。
关键词
大黄蛰虫丸
糖尿病肾病
网络药理学
分子对接技术
Dahuang Zhechong pill
diabetic kidney disease
network pharmacology
molecular docking technology
