理脾降浊方治疗2型糖尿病的网络药理学和蛋白质组学研究
Network Pharmacology and Proteomics Reveal the Mechanism of Lipi Jiangzhuo Formula in Treating Type 2 Diabetes Mellitus
潘琳琳 1相宏杰 2逯艳婷 1刘桂荣1
作者信息
- 1. 山东中医药大学中医学院,济南,250355
- 2. 山东第一医科大学第一附属医院中医科,济南,250013
- 折叠
摘要
目的:研究理脾降浊方(LPJZF)治疗2型糖尿病(T2DM)的潜在分子机制.方法:首先,基于网络药理学筛选出LPJZF中的活性成分和作用靶点,通过基因表达综合数据库筛选出与T2DM相关的差异表达基因,并运用蛋白质-蛋白质相互作用、基因本体(GO)和京都基因与基因组百科全书(KEGG)分析LPJZF在治疗T2DM中的作用靶点和通路.其次,用LPJZF对T2DM大鼠进行干预,采用蛋白质组学鉴定差异蛋白,然后用KEGG和GO分析探究LPJZF干预T2DM的潜在机制.最后,运用分子对接技术评估T2DM潜在靶点与LPJZF活性成分之间的结合亲和力.结果:网络药理学分析共筛选出LPJZF干预T2DM的63个有效成分和135个靶点;蛋白质组学共鉴定出LPJZF干预T2DM的964个差异表达蛋白,以及磷脂酰肌醇3激酶/蛋白激酶B(PI3K-AKT)、丝裂原活化蛋白激酶(MAPK)、核因子κB和叉头框蛋白O(FoxO)等4条关键通路;分子对接结果显示,T2DM相关蛋白细胞周期蛋白依赖性激酶2(CDK2)、表皮生长因子受体(EGFR)、肿瘤蛋白P53(TP53)、热休克蛋白90 kDa αA类成员1(HSP90AA1)和小鼠双微体2(MDM2)与LPJZF中的黄芩素、芒柄花黄素、山柰酚、汉黄芩素、β-谷甾醇和豆甾醇具有良好的亲和力.结论:LPTZF能有效改善胰岛素抵抗,促进胰腺B细胞再生,是治疗T2DM的有效方剂.
Abstract
Objective:To explore the potential molecular mechanism of Lipi Jiangzhuo Formula(LPJZF)in treating type 2 diabetes mellitus(T2DM).Methods:Firstly,network pharmacology was employed to screen the active components and targets of LPJZF.The T2DM-related targets(differentially expressed genes)were retrieved from the Gene Expression Omnibus.The protein-protein inter-action network of the targets shared by LPJZF and T2DM was established to predict the key targets.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed to predict the pathways involved in the treat-ment of T2DM with LPJZF.The rat model of T2DM was treated with LPJZF,and proteomics was used to identify the differentially expressed proteins.Then,KEGG and GO enrichment analyses were conducted to predict the potential mechanism of the treatment.Finally,the binding affinity between key potential targets and active components was verified by molecular docking.Results:A total of 63 compounds and 135 targets of LPJZF against T2DM were screened out,and 964 differentially expressed proteins were identi-fied to be involved in the treatment.The phosphatidylinositol 3-kinase/protein kinase B(PI3K-AKT),mitogen-activated protein ki-nase(MAPK),nuclear factor kappa-B(NF-κB),and forkhead box O(FoxO)signaling pathways were predicted as the key path-ways in the treatment of T2DM with LPJZF.Molecular docking results revealed that cyclin-dependent kinase 2(CDK2),epidermal growth factor receptor(EGFR),tumor protein P53(TP53),heat shock protein 90 kDa alpha class A member 1(HSP90AA1),and mouse double minute 2(MDM2)possessed good affinity with baicalein,formononetin,kaempferol,wogonin,β-sitosterol,and stig-masterol in LPJZF.Conclusion:LPTZF can ameliorate insulin resistance and promote the regeneration of pancreatic β cells,serving as an effective prescription for treating T2DM.
关键词
理脾降浊方/2型糖尿病/网络药理学/蛋白质组学/分子对接/活性成分/差异蛋白/胰岛素抵抗Key words
Lipi Jiangzhuo Formula/Type 2 diabetes mellitus/Network pharmacology/Proteomics/Molecular docking/Active components/Differentially expressed proteins/Insulin resistance引用本文复制引用
基金项目
国家自然科学基金项目(82104723)
山东省自然科学基金项目(ZR2023QH101)
山东省高等学校"青创团队计划"项目(2022KJ340)
出版年
2024
国家科技期刊平台
NSTL
万方数据