Luo Bo-Yan, Zhou Hong-Su, Xiao Qiu-Xia, He Yu-Qi
School of Pharmacy Zunyi Medical University Zunyi Guizhou China.
Department of Anesthesiology Affiliated Hospital of Zunyi Medical University Zunyi Guizhou China.
Ibrain. 2022 May 5;8(2):127-140. doi: 10.1002/ibra.12033. eCollection 2022 Summer.
Huangqi Guizhi Wuwu Decoction (HGWD) has a definite effect on neuropathic pain (NP), whereas the specific mechanism has not been elucidated. The components and targets in HGWD were collected and identified through System Pharmacology Database (Traditional Chinese Medicine Database and Analysis Platform). Genecards and Online Mendelian Inheritance in Man databases were used to search for NP-related genes. The Venn diagram was drawn to get the intersection target. Cytoscape 3.8.0 software was used to construct the compound-disease-target-pathway networks. STRING database was applied to analyze protein-protein interaction of potential targets. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were used to identify the function of genes related to NP. Finally, molecular docking was performed to visualize the binding mode and affinity between proteins and active ingredients. According to the intersection target of the Venn diagram, the network graph is constructed by Cytoscape and the results show the five compounds, β-sitosterol, (+)-catechin, quercetin, Stigmasterol, kaempferol, and 15 genes (CASP3, FOS, GSK3B, HSP90AA1, IKBKB, IL6, MAPK8, RELA, ICAM1, SELE, ELK1, HSPB1, PRKACA, PRKCA, RAF1) were highly correlated with NP. KEGG and GO of 15 genes results that TNF, IL-17 and MAPK signaling pathway were Significantly related to the pathological mechanism of NP. Molecular docking showed that core genes in this network were IL-6 (TNF and IL-17 signaling pathways), ICAM1 (TNF signaling pathway), and CASP3 (three signal pathways). This study found that the five active compounds, three core genes, and three signaling pathways may be the key to the treatment of NP by HGWD.
黄芪桂枝五物汤（HGWD）对神经性疼痛（NP）有确切疗效，但其具体机制尚未阐明。通过系统药理学数据库（中药数据库与分析平台）收集并鉴定了HGWD中的成分和靶点。利用Genecards和《人类孟德尔遗传在线》数据库搜索与NP相关的基因。绘制维恩图以获得交集靶点。使用Cytoscape 3.8.0软件构建化合物-疾病-靶点-通路网络。应用STRING数据库分析潜在靶点的蛋白质-蛋白质相互作用。使用京都基因与基因组百科全书（KEGG）和基因本体论（GO）分析来确定与NP相关基因的功能。最后，进行分子对接以可视化蛋白质与活性成分之间的结合模式和亲和力。根据维恩图的交集靶点，由Cytoscape构建网络图，结果显示五种化合物，β-谷甾醇、（+）-儿茶素、槲皮素、豆甾醇、山奈酚，以及15个基因（CASP3、FOS、GSK3B、HSP90AA1、IKBKB、IL6、MAPK8、RELA、ICAM1、SELE、ELK1、HSPB1、PRKACA、PRKCA、RAF1）与NP高度相关。15个基因的KEGG和GO结果表明，TNF、IL-17和MAPK信号通路与NP的病理机制显著相关。分子对接显示，该网络中的核心基因是IL-6（TNF和IL-17信号通路）、ICAM1（TNF信号通路）和CASP3（三条信号通路）。本研究发现，这五种活性化合物、三个核心基因和三条信号通路可能是HGWD治疗NP的关键。
