基于网络药理学探讨槲皮素联合山柰酚治疗DPN的作用机制

Explore the Mechanism of Quercetin Combined with Kaempferol in the Treatment of DPN based on Network Pharmacology

目的探索槲皮素(Quercetin,Que)联合山柰酚(Kaempferol,Kae)防治糖尿病周围神经病变(Diabetic peripheral neuropathy,DPN)的潜在作用机制。方法运用多个数据库(TCMSP,Uniprot,GeneCards,DisGeNET,OMIM,PharmGKB,Drugbank String)收集药物和疾病靶点,借助软件(“Venny”,Cytoscape 3.8.0,ClusterProfiler R)创建交汇基因、构建网络图、确定关键基因和进行富集分析。结果筛选出157个药物作用靶点和2084个疾病关联基因,有94个交集基因,其中TNF、AKT1、IL-6等18个基因被确定为关键基因。关键基因GO富集到BP共计1619条,与细胞应激、细胞增殖、抗氧化等过程有关;CC共计27个,主要是筏膜、膜微区和质膜筏等细胞结构;MF共计46条,涉及到磷酸酶结合,细胞因子受体结合,以及生长因子受体结合等功能。KEGG富集到147条通路,关键靶点主要集中在胰腺癌、AGE-RAGE信号通路和TNF信号通路中。结论Que联合Kae通过调节炎症反应、氧化应激、细胞凋亡或增殖发挥防治作用,体现出其多靶点和多通路特点,为进一步揭示其药理机制提供新思路和明确老药新用的方向。

Objective To explore the potential mechanism of quercetin(Que)combined with kaempferol(Kae)in the prevention and treatment of diabetic peripheral neuropathy(DPN).Methods Multiple databases(TCMSP,Uniprot,GeneCards,DisGeNET,OMIM,PharmGKB and Drugbank String)were used to collect drugs and disease targets.Software("Venny",Cytoscape3.8.0,ClusterProfiler R)was used to create intersection genes,construct network diagrams,determine key genes and perform enrichment analysis.Results A total of 157 drug targets and 2084 disease-related genes were screened,and 94 intersection genes were identified.Among them,18 genes were identified as key genes,such as TNF,AKT1 and IL-6.A total of 1619 BP were enriched in the key gene GO,which were related to cellular response to chemical stress,response to oxidative stress,epithelial cell proliferation and other processes.There were 27 CC in total,which were mainly membrane raft,membrane microdomain,caveola,et al.A total of 46 MF was involved in phosphatase binding,cytokine receptor binding and growth factor receptor binding.KEGG enriched 147 pathways,and the key targets were mainly concentrated in pancreatic cancer,AGE-RAGE signaling pathway and TNF signaling pathway.Conclusion The combination of Que and Kae plays a preventive and therapeutic role by regulating inflammatory response,oxidative stress,cell apoptosis or proliferation,reflecting its multi-target and multi-pathway characteristics,which provides new ideas for further revealing its pharmacological mechanism and new directions for the use of old drugs.