基于网络药理学探析鬼箭羽治疗2型糖尿病潜在分子机制

Potential molecular mechanism of Euonymus alatus in the treatment of type 2 diabetes based on network pharmacology

目的:应用网络药理学方法研究鬼箭羽治疗2型糖尿病的潜在分子机制。方法:检索相关文献和中药系统药理学数据库与分析平台(TCMSP),筛选鬼箭羽主要活性成分及作用靶点,检索GeneCards和OMIM数据库获得2型糖尿病的靶点数据集,整合药物与疾病的交集靶点,借助Cytoscape软件构建“药物‑成分‑靶点‑疾病”网络模型,运用STRING平台绘制蛋白与蛋白相互作用(PPI)网络,同时对鬼箭羽治疗2型糖尿病的相关靶点进行基因功能和代谢通路富集分析。结果:经筛选得到8种主要活性成分和154个药物‑疾病共同作用靶点,其中JUN、MAPK1、AKT1、RELA、IL6等可能是鬼箭羽治疗2型糖尿病的核心调控基因。GO富集分析共得到153条生物过程,主要包括核受体活性、转录因子活性直接配体调节序列特异性DNA结合、类固醇激素受体活性、细胞因子受体结合等。KEGG分析共富集到156条显著通路,主要包括AGE‑RAGE信号通路、流体剪切应力与动脉粥样硬化、乙型肝炎、前列腺癌、卡波西肉瘤相关疱疹病毒感染等。结论:基于网络药理学的研究表明,鬼箭羽中槲皮素、山奈酚等多种活性成分,可作用于JUN、MAPK1、AKT1、RELA、IL6等多个靶点,通过协同调节糖脂代谢、降低胰岛素抵抗、保护胰岛β细胞功能、抗氧化应激、抗炎修复等多个途径发挥治疗2型糖尿病及相关并发症的作用。

Objective:To investigate the potential molecular mechanism of Guijianyu(Euonymus alatus)in the treatment of type 2 diabetes by network pharmacology approach.Methods:Relevant literature and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)were searched to screen the main active ingredients and targets of Guijianyu.The GeneCards and OMIM databases were searched to obtain target datasets for type 2 diabetes.and sort out the intersection targets of drug and disease.The"drug‑ingredient‑target‑disease"network model was constructed with the help of Cytoscape software,the protein‑protein interaction(PPI)network was drawn using the STRING platform,and gene function and metabolic pathway enrichment analysis were also performed on the relevant targets of Guijianyu in the treatment of type 2 diabetes.Results:After screening,8 main active ingredients and 154 drug‑disease common targets were obtained,of which JUN,MAPK1,AKT1,RELA,and IL6 may be the key regulatory genes of Guijianyu in the treatment of type 2 diabetes.GO enrichment analysis yielded a total of 153 biological processes,mainly including nuclear receptor activity,transcription factor activity,direct ligand regulated sequence‑specific DNA binding,steroid hormone receptor activity,cytokine receptor binding.KEGG analysis was enriched to a total of 156 significant pathways,mainly including AGE‑RAGE signaling pathway in diabetic complications,fluid shear stress and atherosclerosis,hepatitis B,prostate cancer,kaposi sarcoma‑associated herpesvirus infection.Conclusions:This study based on network pharmacology showed that various active ingredients such as quercetin and kaempferol in Guijianyu could act on multiple targets such as JUN,MAPK1,AKT1,RELA,and IL6.It may play a role in the treatment of type 2 diabetes and related complications by synergistically regulating glucose and lipid metabolism,reducing insulin resistance,protecting pancreatic beta‑cell function,anti‑oxidative stress,and anti‑inflammatory repair and so on.