背景:中药配对白及五倍子(BS-GC)是治疗慢性皮肤溃疡(CSU)的经典外用中药配方组合。
目的:本研究的目的是探索BS-GC的有效活性成分,以及其对CSU作用的核心靶标和信号转导途径。
方法:BS-GC的成分从TCMSP和HERB数据库获得。从SwissTargetPrediction数据库检索所有活性成分的靶标。CSU的目标是从OMIM获得的,GeneCards,药店,和DisGeNET数据库。构建了药物-疾病靶蛋白-蛋白相互作用(PPI)网络,以选择最核心的利用Cytoscape3.7.2建立了一个草药-成分-目标网络。此外,我们进行了基因本体论(GO)和京都基因百科全书和基因组数据库(KEGG)分析,并通过分子对接验证了网络药理学的结果.
结果:初步筛选了来自草药对BS-GC的总共40种活性成分,共检索到528个目标。同时,CSU目标总数为1032。然后,BS-GC和CSU之间的共同目标数量为107个。根据PPI网络筛选出带有CSU的草药对BS-GC的13个核心靶标,包括AKT1,TNF,EGFR,BCL2,HIF1A,MMP-9等。5个主要核心活性成分是1-(4-羟基苄基)-2-甲氧基-9,10-二氢菲-4,7-二醇,1-(4-羟基苄基)-4-甲氧基-9,10-二氢菲-2,7-二醇,physcion,二氢杨梅素,还有杨梅素.主要的生物过程是炎症,氧化应激,和免疫反应,涉及糖尿病并发症的AGE-RAGE信号通路,HIF-1信号通路,NF-κB信号通路,和钙信号通路。分子对接结果显示5种主要核心活性成分与13种核心靶标之间具有良好的结合活性。
结论:本研究预测了CSU治疗的核心靶点和信号转导通路,为进一步的分子机制研究提供参考。
BACKGROUND: Herb pair Bletilla striata-Galla chinensis (BS-GC) is a classic combination of topical traditional Chinese medicine formulae in the treatment of chronic skin ulcers (CSUs).
OBJECTIVE: The aim of this study is to explore the effective active ingredients of BS-GC, as well as the core targets and signal transduction pathways of its action on CSUs.
METHODS: The ingredients of BS-GC were obtained from TCMSP and HERB databases. The targets of all active ingredients were retrieved from the SwissTargetPrediction database. The targets of CSUs were obtained from OMIM, GeneCards, Drugbank, and DisGeNET databases. A drug-disease target protein-protein interaction (PPI) network was constructed to select the most core targets, and an herb-ingredient-target network was built by utilizing Cytoscape 3.7.2. Furthermore, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes database (KEGG) analysis and verified the results of network pharmacology through molecular docking.
RESULTS: A total of 40 active ingredients from the herb pair BS-GC were initially screened, and a total of 528 targets were retrieved. Meanwhile, the total number of CSU targets was 1032. Then, the number of common targets between BS-GC and CSUs was 107. The 13 core targets of herb pair BS-GC with CSUs were filtered out according to the PPI network, including AKT1, TNF, EGFR, BCL2, HIF1A, MMP-9, etc. The 5 main core active ingredients were 1-(4-Hydroxybenzyl)-2-methoxy-9,10-dihydrophenanthrene-4,7-diol, 1-(4- Hydroxybenzyl)-4-methoxy-9,10-dihydrophenanthrene-2,7-diol, physcion, dihydromyricetin, and myricetin. The main biological processes were inflammation, oxidative stress, and immune response, involving the AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway, NF-κB signaling pathway, and calcium signaling pathway. Molecular docking results showed good binding activity between the 5 main core active ingredients and 13 core targets.
CONCLUSIONS: This study predicted the core targets and signal transduction pathways in the treatment of CSUs to provide a reference for further molecular mechanism research.