基于网络药理学和实验验证研究柠檬精油缓解焦虑症的作用机制

Mechanism of lemon essential oil in mitigation of anxiety based on network pharmacology and experimental validation

基于网络药理学方法探讨柠檬精油(lemon essential oil,LEO)干预焦虑症的作用机制并进行实验验证。GC-MS测定LEO组成,从TCMSP平台挖掘LEO的作用靶点;利用OMIM、GeneCards数据库获得焦虑症靶点;利用Venny获得LEO-焦虑症的交集靶点,进行GO和KEGG富集;利用Cytoscape构建“成分-靶点-通路-疾病”网络,利用1-Click Docking对关键成分与靶点进行分子对接。利用细胞炎症模型进行验证。从构建的网络中得到LEO的19种活性成分如柠檬烯、α-松油醇、β-蒎烯、乙酸橙花酯、4-萜品醇等,通过作用于18个疾病靶点(占总靶点78.26%)如GABRA2、MAO、DRD1、GRIA2等,调控20条信号通路如神经活性配体-受体相互作用、羟色胺能突触、多巴胺能突触等。柠檬精油对DPPH、ABTS自由基有抑制作用,能降低由脂多糖(lipopolysaccharide,LPS)诱导HaCaT细胞内活性氧(reactive oxygen species,ROS)水平,降低炎症因子NO、TNF-α及IL-6水平。LEO通过多种有效成分多靶点调控多条信号通路降低细胞氧化应激、抑制炎症反应,从而干预焦虑症。

The mechanism of lemon essential oil(LEO)intervention in anxiety disorder was investigated using network pharmacology,and its efficacy was validated through experimental verification.The composition of LEO was determined by GC-MS,and the target compounds in LEO were identified from the Traditional Chinese Medicine Systems Pharmacology(TCMSP)platform.The target for anxiety disorder was obtained from the OMIM and GeneCards databases.The intersection target of LEO-anxiety disorder was determined using Venny,and subsequent enrichment analyses were performed for GO and KEGG pathways.The"component-target-pathway-disease"network was constructed using Cytoscape,and the key components were subjected to target docking through 1-Click Docking.The cellular inflammation model was employed for validation.The constructed network identified a total of nineteen active components in LEO,including limonene,α-terpineol,β-pinene,neroli acetate,4-terpinol,and others.The compound exerts its effects on 18 disease targets,thereby modulating 20 signaling pathways including neuroactive ligand-receptor interaction,serotonergic synapses,and dopaminergic synapsesamong others.The eighteen disease targets accounted for 78.26%of the total target count,including GABRA2,MAO,DRD1,GRIA2,etc.The LEO demonstrates inhibitory effects on DPPH and ABTS free radicals,suppresses the generation of reactive oxygen species in Lipopolysaccharide-induced HaCaT cells,and reduces the levels of inflammatory factors NO,TNF-α,and IL-6.The various active components of LEO can modulate multiple signaling pathways through interactions with multiple targets,thereby attenuating cellular oxidative stress,suppressing inflammatory responses,and ultimately intervening in anxiety disorders.