Gholais Noha Saleh, Shi Chunrui, Zhang Jing, Liao Bei, Albarmaqi Rowida A, Tang Xiaolong, Mi Leyuan
Department of Dermatology, The First Hospital of Lanzhou University, Lanzhou City, Gansu Province, China.
The First Clinical Medical College, Lanzhou University, Lanzhou City, Gansu Province, China.
Evid Based Complement Alternat Med. 2022 Jul 13;2022:6944792. doi: 10.1155/2022/6944792. eCollection 2022.
JinGuanLan (JGL) formula is a traditional Chinese medicine (TCM) developed by the Department of Pharmacology at the First Hospital of Lanzhou University. The network pharmacology approach was applied to determine the potential active compounds, therapeutic targets, and main pathways of the JGL formula to evaluate its application value in acne vulgaris.
Data on the active compounds and their related targets were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Acne vulgaris-related targets were searched from the Online Mendelian Inheritance in Man (OMIM) database, GeneCards Database, Comparative Toxicogenomics Database (CTD), Therapeutic Target Database (TTD), and DisGeNET Database. Targets intersecting between JGL- and acne vulgaris-related targets were chosen as potential therapeutic targets. The protein-protein interaction (PPI) network of potential therapeutic targets was visualized using Cytoscape software based on the PPI data collected from the STRING database. Three topological features, namely, "Degree," "MCC," and "EPC" of each node in the PPI network were calculated using the cytoHubba plugin of Cytoscape to excavate the core targets. R program was used for the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the potential therapeutic targets. Finally, the compound-target-pathway network was constructed.
Among the 148 active compounds that were identified, quercetin and kaempferol showed the highest degree of target interaction and thus may play essential roles in the pharmacological effect of the JGL formula for acne treatment. Among the 97 potential therapeutic targets that were screened out, the 6 core targets were TNF, JUN, IL6, STAT3, MAPK1, and MAPK3. A total of 2260 terms of GO enrichment analysis were obtained, including 2090 for biological processes (BP), 37 for cellular components (CC), and 133 for molecular function (MF). A total of 156 enriched KEGG pathways were identified, including TNF, IL-17, Th17 cell differentiation, MAPK, PI3K-Akt, T cell receptor, and Toll-like receptor signalling pathways.
This work showed that the JGL formula might reverse the pathological changes associated with acne vulgaris through its antiinflammatory effect and regulate the excessive lipogenesis in sebaceous glands via different signalling pathways. This new drug has application value and is worthy of further research and development.
金冠蓝(JGL)配方是兰州大学第一医院药理学系研发的一种中药。采用网络药理学方法确定JGL配方的潜在活性成分、治疗靶点和主要通路,以评估其在寻常痤疮中的应用价值。
从中药系统药理学数据库与分析平台(TCMSP)获取活性成分及其相关靶点的数据。从人类孟德尔遗传在线(OMIM)数据库、基因卡片数据库、比较毒理基因组学数据库(CTD)、治疗靶点数据库(TTD)和疾病基因数据库(DisGeNET)中搜索寻常痤疮相关靶点。选取JGL相关靶点与寻常痤疮相关靶点的交集作为潜在治疗靶点。基于从STRING数据库收集的蛋白质-蛋白质相互作用(PPI)数据,使用Cytoscape软件可视化潜在治疗靶点的PPI网络。使用Cytoscape的cytoHubba插件计算PPI网络中每个节点的三个拓扑特征,即“度”“MCC”和“EPC”,以挖掘核心靶点。使用R程序对潜在治疗靶点进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析。最后,构建化合物-靶点-通路网络。
在鉴定出的148种活性成分中,槲皮素和山奈酚显示出最高的靶点相互作用程度,因此可能在JGL配方治疗痤疮的药理作用中发挥重要作用。在筛选出的97个潜在治疗靶点中,6个核心靶点为TNF、JUN、IL6、STAT3、MAPK1和MAPK3。共获得2260个GO富集分析术语,包括2090个生物过程(BP)、37个细胞成分(CC)和133个分子功能(MF)。共鉴定出156条富集的KEGG通路,包括TNF、IL-17、Th17细胞分化、MAPK、PI3K-Akt、T细胞受体和Toll样受体信号通路。
本研究表明,JGL配方可能通过其抗炎作用逆转寻常痤疮相关的病理变化,并通过不同信号通路调节皮脂腺中过度的脂肪生成。这种新药具有应用价值,值得进一步研发。