基于网络药理学探究黄芪赤风汤治疗糖尿病周围神经病变作用机制

To Explore the Mechanism of Huangqi Chifeng Decoction in the Treatment of Diabetic Peripheral Neuropathy Based on Network Pharmacology

摘要: 目的：通过网络药理学探究黄芪赤风汤有效成分、糖尿病周围神经病变之间的网络关系，探究黄芪赤风汤作用机制。方法：通过中药系统药理学数据库分析平台(TCMSP)筛选复方黄芪赤风汤有效成分及相应的靶点；从Gene Cards数据库中获取糖尿病周围神经病变疾病相关靶点；使用在线软件平台Venny 2.1绘制药物、疾病的交集靶点维恩图；通过Metoscape数据库对交集靶点进行基因本体功能(GO)和京都基因与基因组百科全书(KEGG)通路富集分析；通过STRING在线数据库构建PPI网络，同时导入Cytoscape 3.9.1获取核心靶点；通过Cytoscape 3.9.1绘制活性成分–靶点网络。结果：黄芪赤风汤29种活性成分，共作用于232个靶点；疾病靶点1286个，疾病和药物交集靶点94个；核心靶点包括肿瘤坏死因子(TNF)、血管内皮生长因子A (VEGFA)、白细胞介素6 (IL6)、TP53、雌激素受体1 (ESR1)、蛋白激酶Bα (AKT1)、过氧化物酶(CAT)、胱天蛋白酶3 (CASP3)、过氧化物酶体增殖物激活受体γ (PPARG)、低聚果糖(FOS)等；GO富集分析在BP上主要为细胞对氧化应激、活性氧、脂质等的生物学过程，在CC上表现为细胞膜、膜微区、膜筏等结构的细胞定位，在MF上表现为肾上腺素能受体、细胞因子、配体激活转录因子等分子功能；KEGG富集分析主要包括糖尿病并发症的AGE-RAGE信号通路、流体剪切应力与动脉粥样硬化、脂质和动脉粥样硬化、癌症中的蛋白聚糖、磷脂酰肌醇3-激酶(PI3K)/蛋白激酶(Akt)信号通路、IL-17信号通路、TNF信号通路、MAPK信号通路、活性氧、HIF-1信号通路等通路。结论：黄芪赤风汤有效成分可能通过各类氧化应激、炎症相关通路作用于糖尿病周围神经病变。

Abstract: Objective: To explore the network relationship between the active components of Huangqi Chifeng Decoction and diabetic peripheral neuropathy through network pharmacology, and explore the action mechanism of Huangqi Chifeng Decoction. Methods: The effective components and corresponding targets of compound Huangqi Chifeng Decoction were screened by TCMSP. Targets related to diabetic peripheral neuropathy were obtained from GeneCards database. Venny2.1, an online software platform, was used to draw the Venn diagram of intersecting targets of drugs and diseases. Metoscape database was used to enrich gene ontology function (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for intersection targets. PPI network was constructed using STRING online database, and Cytoscape3.9.1 was imported to obtain core targets. Map the Active Ingredient-Target network via Cytoscape3.9.1. Results: There were 29 active ingredients of Huangqi Chifeng decoction, which acted on 232 targets. There were 1286 disease targets and 94 disease and drug intersection targets. Core targets include tumor necrosis factor (TNF), vascular endothelial growth factor A (VEGFA), interleukin 6 (IL6), TP53, estrogen receptor 1 (ESR1), protein kinase Bα (AKT1), peroxidase (CAT), caspase 3 (CASP3), and peroxisome proliferator-activated receptor γ (PP) ARG), oligosaccharides (FOS), etc. In BP, GO enrichment analysis is mainly the biological process of cells to oxidative stress, reactive oxygen species, lipids, etc. In CC, it is the cell localization of cell membrane, membrane microregion, membrane raft, etc. In MF, it is the molecular function of adrenergic receptors, cytokines, ligand-activated transcription factors, etc. KEGG enrichment analysis mainly included AGE-RAGE signaling pathway in diabetes complications, fluid shear stress and atherosclerosis, lipid and atherosclerosis, proteoglycan in cancer, phosphatidylinositol 3-kinase (PI3K)/protein kinase (Akt) signaling pathway, IL-17 signaling pathway, TNF signaling pathway, and MAPK signaling pathway Pathway, reactive oxygen species, HIF-1 signaling pathway, etc. Conclusion: The active components of Huangqi Chifeng decoction may act on diabetic peripheral neuropathy through various pathways related to oxidative stress and inflammation.