摘要
目的整合类药性和网络靶标对当归补血加味汤(DBJD)防治糖尿病视网膜病变(DR)的靶标和通路进行初步的预测和探讨。方法利用超高效液相色谱仪联用四级杆串联飞行时间高分辨率质谱(UPLC-Q-TOF/HRMSE)分析技术鉴定该汤药中的化学成分,并基于相关网站对所鉴定的成分进行类药性筛选。在此基础上,在PharmMapper网站对所筛选成分进行靶标预测,并利用CTD、TTD、GeneCards网站寻找DR的作用靶标。将成分靶标与疾病靶标网络进行整合并基于大网络的DC、CC、BC值进行核心靶标群筛选,在核心靶标群的基础上进行间接靶标的筛查,建立潜在作用靶标的相关网络并确立关键靶标。将关键靶标与所筛成分进行反向分子对接验证,并对所有潜在作用靶标进行基因本体(GO)生物分析、京都基因和基因组百科全书数据库(KEGG)通路分析和Reactome通路分析,最终获得"方剂-药材-成分-直接靶标-间接靶标-通路"的整合大网络。结果基于UPLC-Q-TOF/HRMSE分析技术共鉴定出55个化学成分,类药性筛选后获得33个成分。核心靶标群由36个靶标构成,以此钓取了20个间接靶标,通过比较degree值最终确定了AKT1、MAPK3、VEGFA、INS、MAPK1和CASP3共6个关键靶标。分子对接显示关键靶标与丹参酮Ⅰ、丹酚酸B、人参皂苷Rg1、三七皂苷R1、丹参酮ⅡA等多个质控成分结合活性良好。通路分析结果提示,DBJD可能通过调节氧化应激、炎症因子、糖代谢等对DR进行干预。结论基于类药性和网络靶标对复杂中药成分作用机制进行精准预测有利于改善既往研究过程的盲目性并加快中药的现代化研究进程。本研究进行了DBJD防治DR分子机制的初步探讨,对今后的深入研究具有一定的参考价值。
Objective Integrating drug-likeness and network targets to preliminarily predict and explore the targets and pathways of Danggui Buxue Jiawei decoction(DBJD)in the prevention and treatment of diabetic retinopathy(DR).Methods The chemical constituents of DBJD were identified by UPLC-Q-TOF/HRMSEanalytical techniques. The related websites were used to estimate the drug-likeness for all identified constituents. Then,for the selected drug-like constituents,targets-predicting was carried out on PharmMapper,and the targets for DR were searched by CTD,TTD and GeneCards. The component-target and disease-target networks were integrated to establish a large network,and core targets were searched on the basis of the DC,CC and BC values of the large network. Moreover,indirect targets were further searched on the basis of the core targets. Then,an all potential targets-related network was constructed and related key targets were searched by the constructed network. The key targets were verified by docking with the related components. Gene ontology(GO)biological analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis and Reactome pathway analysis were carried out on all potential targets. Eventually,a large Prescription-Medicinal materialComponent-Direct target-Indirect target-Pathway integrated network was established for the DBJD studies.Results A total of 55 chemical constituents were identified by UPLC-Q-TOF/HRMSE. Among them,33 components were selected by the drug-likeness estimation. The core targets consisted of 36 targets,and 20 indirect targets were obtained by relating with the core targets. By comparing degree values,6 key targets were established:AKT1,MAPK3,VEGFA,INS,MAPK1 and CASP3. In molecular docking tests,these key targets showed good binding activities with tanshinoneⅠ,salvianolic acid B,ginsenoside Rg1,notoginsenoside R1,tanshinoneⅡAand other quality control components. Pathway analysis suggested that DBJD could likely interfere with the diabetic retinopathy by regulating oxidative stress,i
作者
周佳丽
袁付丽
韩霜
何涛
王文鑫
姚柯男
崔曦兮
刘传鑫
ZHOU Jia-li;YUAN Fu-li;HAN Shuang;HE Tao;WANG Wen-xin;YAO Ke-nan;Cui Xi-xi;LIU Chuan-xin(School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 100029,China)
出处
《国际药学研究杂志》
CAS
北大核心
2020年第1期33-50,共18页
Journal of International Pharmaceutical Research
基金
国家自然科学基金资助项目(81774014)。
关键词
当归补血加味汤
糖尿病视网膜病变
类药性
网络靶标
分子机制
Danggui Buxue Jiawei decoction
diabetic retinopathy
drug-likeness
network target
molecular mechanism
