基于网络药理学与GC-MS探讨竹叶花椒挥发油干预高脂血症的作用机制

Investigation of the Mechanism of Volatile Oil from Zanthoxylum Armatum DC. in Intervening Hyperlipidemia Based on Network Pharmacology and GC-MS

目的基于气相色谱-质谱联用结合网络药理学方法,探讨竹叶花椒挥发油干预高脂血症的活性成分及作用机制,为竹叶花椒挥发油中功能性成分研究及其干预高脂血症的作用机制提供理论基础。方法首先通过GC-MS鉴定竹叶花椒挥发油的化学成分,再借助数据库获取化学成分对应靶点和高脂血症疾病靶点。又通过Venn图、蛋白-蛋白相互作用分析、GO分析、KEGG代谢通路富集分析和构建“靶点-通路-活性成分”网络得到竹叶花椒挥发油干预高脂血症的关键靶点。最后采用分子对接软件AutoDock对竹叶花椒挥发油主要活性化合物与关键靶点进行半柔性对接验证。结果在竹叶花椒挥发油中鉴定出29个化学成分,得到37个干预高脂血症的核心靶点,该核心靶点涉及细胞对脂质的反应、脂质的定位调节和对脂多糖的反应等方面。KEGG富集分析与“靶点-通路-活性成分”网络进一步得到PPARA、RXRA、TNF、NR1H3、PPARG和IL-6等28个关键靶点,也得到金合欢醇、亚油酸和α-石竹烯等7个主要活性成分。分子对接结果表明关键靶点与主要活性成分有较好的结合能力,结合能均小于-7.0 kJ/mol。结论竹叶花椒挥发油中的多种功能性成分可能通过作用关键靶点PPARA、RXRA、TNF、NR1H3、PPARG和IL-6以起到干预高脂血症的作用。本研究探讨了竹叶花椒挥发油干预高脂血症的作用机制,期望为竹叶花椒挥发油中功能性成分的进一步研究提供理论支撑。

Objective Based on gas chromatography-mass spectrometry(GC-MS)combined with network pharmacology methods,this study explored the active ingredients and mechanisms of the volatile oil from Zanthoxylum armatum DC.in intervening hyperlipidemia,providing a theoretical basis for the research on functional components in the volatile oil from Zanthoxylum armatum DC.and its intervention mechanism in hyperlipidemia.Methods Initially,the chemical components of the volatile oil from Zanthoxylum armatum DC.were identified by GC-MS,and then the corresponding targets of the chemical components and the disease targets of hyperlipidemia were obtained through databases.The key targets of the volatile oil from Zanthoxylum armatum DC.in intervening hyperlipidemia were obtained through Venn diagram,protein-protein interaction analysis,GO analysis,KEGG metabolic pathway enrichment analysis,and construction of the“target-pathway-active ingredient”network.Finally,the molecular docking software AutoDock was used to validate the semi-flexible docking of the main active compounds from the volatile oil from Zanthoxylum armatum DC.with the key targets.Results 29 chemical components were identified in the volatile oil from Zanthoxylum armatum DC.,obtaining 37 core targets for intervening hyperlipidemia,which are involved in cellular responses to lipids,lipid localization regulation,and responses to lipopolysaccharides.Through KEGG enrichment analysis and the“target-pathway-active ingredient”network,28 key targets including PPARA,RXRA,TNF,NR1H3,PPARG,and IL-6,as well as 7 main active ingredients such as farnesol,linoleic acid,andα-caryophyllene were obtained.The molecular docking results showed that the key targets had good binding abilities with the main active ingredients,with binding energies all less than-7.0 kJ/mol.Conclusion Various functional components in the volatile oil from Zanthoxylum armatum DC.may intervene hyperlipidemia by acting on key targets such as PPARA,RXRA,TNF,NR1H3,PPARG,and IL-6.This study explores the mechanism of the volatile oil from Zanthoxylum armatum DC.in intervening hyperlipidemia,aiming to provide theoretical support for further research on the functional components in the volatile oil from Zanthoxylum armatum DC.