基于GC-MS和生物信息学研究丁香挥发油“启郁开闭”防治银屑病的成分及机制

Composition and mechanism of Caryophylli Flos volatile oil against psoriasis based on GC-MS and bioinformatics

关键词:  丁香  挥发油  银屑病  活性成分  作用机制  GC-MS  生物信息学

Key words:  Caryophylli Flos  volatile oil  psoriasis  active ingredient  mechanism of action  GC-MS  bioinformatics

摘要:

[目的] 通过气相色谱-质谱联用仪（GC-MS）鉴定丁香挥发油的成分，生物信息学预测其可能作用机制。[方法] GC-MS 分析成分后，使用 SwissADME 平台对活性成分进行筛选，通过 Swiss 和 GeneCards 数据库获取这些活性成分与疾病相关的靶点，再通过 Cytoscape 软件构建化合物-靶点网络，采用 String 平台、Cytoscape 软件构建靶点蛋白互作（PPI）网络，筛选关键靶点，将核心靶点导入 DAVID 数据库完成功能富集（GO）和京都基因和基因组百科全书（KEGG）分析，采用 GEO 芯片进行核心靶点的外部验证和 ROC 分析，最后利用 AutoDock 软件进行分子对接验证。[结果] 从丁香挥发油中共鉴定出 10 个主要成分，且均满足“类药五原则”。预测到丝氨酸/苏氨酸蛋白激酶 1（AKT1）、肿瘤坏死因子（TNF）、丝裂原活化蛋白激酶 3（MAPK3）、血管内皮生长因子 A（VEGFA）、酪氨酸蛋白激酶（SRC）、胱天蛋白酶 3（CASP3）等关键靶点，外部验证结果显示 6 个关键靶点表达均具有差异，TNF 具有诊断价值。富集分析得到了 117 个生物过程和 114 条信号通路。分子对接实验显示， 大多数活性成分与其关键靶点具有良好的结合能力。[结论] 丁香挥发油可能通过其中的活性成分如丁香酚等以及关键靶点如 AKT1 等来调控信号传导、蛋白质磷酸化与细胞分化等多个生物学过程，从而协同发挥防治银屑病的作用。

Abstract:

[Objective] The components of Caryophylli Flos volatile oil were identified by GC-MS，and its possible mechanism of action was predicted by network pharmacology. [Methods] After the components were analyzed by GC-MS，the active ingredients were screened using SwissADME platform，and the disease-related targets of these active ingredients were obtained through Swiss and GeneCards databases，and then the compound-target network was constructed by Cytoscape software. String platform and Cytoscape software were used to construct the target PPI network to screen the key targets，and the core targets were imported into DAVID database to complete GO and KEGG analysis，and finally AutoDock software was used for molecular docking verification. [Results] A total of 10 major components were identified from the volatile oil of Caryophylli Flos，and all of them met the “five principles of drug-like”. The hub genes such as AKT1，TNF，MAPK3，VEGFA，SRC，and CASP3 were predicted，and external validation results showed differences in the expression of all six hub genes，TNF had diagnostic value. Enrichment analysis yielded 117 biological processes and 114 signaling pathways. Molecular docking experiments showed that most of the active ingredients have good binding ability with their key targets. [Conclusion] Caryophylli Flos volatile oil may regulate signaling，protein phosphorylation and cell differentiation through its active ingredients such as eugenol and key targets such as AKT1，thus synergistically exerting its effects against psoriasis.