Graduate School, Hebei North University, Zhangjiakou, 075000, China.
Department of Dermatology, Air Force Medical Center, PLA, Beijing, 100142, China.
Sci Rep. 2023 Mar 8;13(1):3884. doi: 10.1038/s41598-023-29207-6.
Coronavirus disease 2019 (COVID-19) is spreading rapidly around the world. However, the treatment of vitiligo combined with COVID-19 has not been reported. Astragalus membranaceus (AM) has a therapeutic effect on patients with vitiligo and COVID-19. This study aims to discover its possible therapeutic mechanisms and provide potential drug targets. Using the Chinese Medicine System Pharmacological Database (TCMSP), GEO database and Genecards websites and other databases, AM target, vitiligo disease target, and COVID-19 related gene set were established. Then find the crossover genes by taking the intersection. Then use GO, KEGG enrichment analysis, and PPI network to discover its underlying mechanism. Finally, by importing drugs, active ingredients, crossover genes, and enriched signal pathways into Cytoscape software, a "drug-active ingredient-target signal pathway-" network is constructed. TCMSP screened and obtained 33 active ingredients including baicalein (MOL002714), NEOBAICALEIN (MOL002934), Skullcapflavone II (MOL002927), and wogonin (MOL000173), which acted on 448 potential targets. 1166 differentially expressed genes for vitiligo were screened by GEO. CIVID-19 related genes were screened by Genecards. Then by taking the intersection, a total of 10 crossover genes (PTGS2, CDK1, STAT1, BCL2L1, SCARB1, HIF1A, NAE1, PLA2G4A, HSP90AA1, and HSP90B1) were obtained. KEGG analysis found that it was mainly enriched in signaling pathways such as IL-17 signaling pathway, Th17 cell differentiation, Necroptosis, NOD-like receptor signaling pathway. Five core targets (PTGS2, STAT1, BCL2L1, HIF1A, and HSP90AA1) were obtained by analyzing the PPI network. The network of "active ingredients-crossover genes" was constructed by Cytoscape, and the 5 main active ingredients acting on the 5 core crossover genes acacetin, wogonin, baicalein, bis2S)-2-ethylhexyl) benzene-1,2-dicarboxylate and 5,2'-Dihydroxy-6,7,8-trimethoxyflavone. The core crossover genes obtained by PPI and the core crossover genes obtained by the "active ingredient-crossover gene" network are intersected to obtain the three most important core genes (PTGS2, STAT1, HSP90AA1). AM may act on PTGS2, STAT1, HSP90AA1, etc. through active components such as acacetin, wogonin, baicalein, bis2S)-2-ethylhexyl) benzene-1,2-dicarboxylate and 5,2'-Dihydroxy-6,7,8-trimethoxyflavone to activate IL-17 signaling pathway, Th17 cell differentiation, Necroptosis, NOD-like receptor signaling pathway, Kaposi sarcoma-associated herpesvirus infection, and VEGF signaling pathway and other signaling pathways to achieve the effect of treating vitiligo and COVID-19.
新型冠状病毒病(COVID-19)正在全球范围内迅速传播。然而,尚未报道白癜风合并 COVID-19 的治疗方法。黄芪对白癜风合并 COVID-19 患者有治疗作用。本研究旨在发现其可能的治疗机制,并提供潜在的药物靶点。使用中药系统药理学数据库(TCMSP)、GEO 数据库和 Genecards 网站等数据库,建立了 AM 靶点、白癜风疾病靶点和 COVID-19 相关基因集。然后通过取交集找到交叉基因。然后使用 GO、KEGG 富集分析和 PPI 网络发现其潜在机制。最后,将药物、活性成分、交叉基因和富集信号通路导入 Cytoscape 软件,构建“药物-活性成分-靶点-信号通路”网络。TCMSP 筛选并获得 33 种活性成分,包括黄芩素(MOL002714)、新黄芩素(MOL002934)、黄芩素 II(MOL002927)和白杨素(MOL000173),这些成分作用于 448 个潜在靶点。通过 GEO 筛选出 1166 个白癜风差异表达基因。通过 Genecards 筛选 COVID-19 相关基因。然后通过取交集,共得到 10 个交叉基因(PTGS2、CDK1、STAT1、BCL2L1、SCARB1、HIF1A、NAE1、PLA2G4A、HSP90AA1 和 HSP90B1)。KEGG 分析发现,它主要富集在 IL-17 信号通路、Th17 细胞分化、坏死性凋亡、NOD 样受体信号通路等信号通路中。通过分析 PPI 网络,获得了 5 个核心靶点(PTGS2、STAT1、BCL2L1、HIF1A 和 HSP90AA1)。通过 Cytoscape 构建“活性成分-交叉基因”网络,获得了作用于 5 个核心交叉基因(白杨素、黄芩素、黄芩素、双(2S)-2-乙基己基)苯-1,2-二羧酸酯和 5,2'-二羟基-6,7,8-三甲氧基黄酮)的 5 种主要活性成分。通过 PPI 获得的核心交叉基因和“活性成分-交叉基因”网络获得的核心交叉基因相交,得到三个最重要的核心基因(PTGS2、STAT1、HSP90AA1)。AM 可能通过白杨素、黄芩素、黄芩素等活性成分作用于 PTGS2、STAT1、HSP90AA1 等,激活 IL-17 信号通路、Th17 细胞分化、坏死性凋亡、NOD 样受体信号通路、卡波西肉瘤相关疱疹病毒感染和 VEGF 信号通路等信号通路,达到治疗白癜风和 COVID-19 的效果。