北京中医药大学学报2018，Vol.41Issue(2)：131-139,9.DOI:10.3969/j.issn.1006-2157.2018.02.007
基于PPARγ-LXRα-ABCA1通路的中药降脂成分研究
Lipid-lowering ingredients in Chinese medicinals based on PPARγ-LXRα-ABCA1 pathway
摘要
Abstract
Objective To discover the potential compounds with lipid-lowering`effect in Chinese medici-nal based on PPARγ-LXRα-ABCA1 pathway by using pharmacophore and molecular docking technology. Methods Firstly, PPARγand LXRαwere selected as search keywords, and the efficacy-identifying models of their agonists were built respectively.The optimal pharmacophore models of PPAR γand LXRα were obtained after validation and evaluation.Traditional Chinese medicine database(TCMD)was se-lected according to the optimal pharmacophore models.The primary screening compounds were retained based on the Lipinski five rules and Fitvalue.Finally,molecular docking was employed to refine the out-comes of pharmacophore model and analyze the binding mode of protein-ligand.The compounds with higher docking scores and amino acids were retained.Results In this study, the optimal model of PPARγagonists was built,which contains one hydrogen bond acceptor,one hydrophobic group and two aromatic rings;The optimal model of LXRαagonists contains two hydrogen bond acceptors, one hydro-phobic group and two aromatic rings.Meanwhile,the crystal structure of PPARγand LXRαbuilt by mo-lecular docking method was used in molecular docking study.According to the pharmacophore and out-comes of Lipinski five rules, there were 22 and 180 compounds obtained respectively.Based on the screening standard of docking studies, the artabotrycinol and hinoki flavone were identified as potential agonists of PPARγ,while anomalamide(artemisia annua)and trichosanatine(trichosanthes rosthornii) were identified as potential agonists of LXR α.These potential compounds could play a key role by acting on the corresponding target in PPAR γ-LXRα-ABCA1 pathway respectively.Conclusion This study pro-vides an efficient method for screening potential agonists of PPAR γand LXRαin TCMD and potential compounds that increase the expression of ABCA 1,which could serve as the candidate compounds in the development of new drugs for hyperlipidemia.关键词
PPARγ-LXRα-ABCA1通路/药效团/分子对接/虚拟筛选/中药Key words
PPARγ-LXRα-ABCA1 pathway/pharmacophore/molecular docking/virtual screening/traditional Chinese materia medica分类
医药卫生引用本文复制引用
赵博文,陈艳昆,张栩,谷宇,张燕玲..基于PPARγ-LXRα-ABCA1通路的中药降脂成分研究[J].北京中医药大学学报,2018,41(2):131-139,9.基金项目
国家自然科学基金资助项目(No.81573831、No.81430094、No.81173522),国家"重大新药创制"科技重大专项(No.2011ZX09401-028)National Natural Science Foundation of China(No.81573831 （No.81573831、No.81430094、No.81173522）
No.81430094 （）
No.81173522),Major Scientific and Technological Project of“Major New Drugs Creation”(No.2011ZX09401-028) （No.2011ZX09401-028）
