目的 探究竹叶椒Zanthoxylum armatum挥发油抗炎、镇痛的活性成分及作用机制。方法 采用气相色谱-质谱联用（GC-MS）定性表征竹叶花椒挥发油成分，并借助中药系统药理学数据库分析平台（TCMSP）、PubChem、Swiss Target Prediction和Uniprot数据库收集活性成分对应靶点。通过GisGeNET及OMIM数据库筛选炎性反应和疼痛的相关靶点，采用Cytoscape软件构建"成分-靶点-疾病"网络。借助STRING及BioGPS数据库构建蛋白-蛋白相互作用（protein-protein interaction，PPI）网络并分析靶点组织分布，运用DAVID数据库对靶点进行基因本体论（gene ontology，GO）功能及京都基因及基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）通路富集分析。采用分子对接法验证竹叶花椒挥发油主要活性成分与核心靶点的相互作用。结果 从竹叶椒挥发油中鉴定成分44个，预测得到其潜在抗炎、镇痛靶点78个，关键靶点涉及前列腺素内过氧化物合成酶2（prostaglandin-endoperoxide synthase 2，PTGS2）、毒蕈碱型乙酰胆碱受体亚型3（muscarinic acetylcholine receptor M3，CHRM3）、过氧化物酶体增殖物激活受体α（peroxisome proliferator activated receptor α，PPARA）、大麻素受体2（cannabinoid receptor 2，CNR2）等。GO分析结果表明筛选得到的靶点主要涉及RNA聚合酶II启动子转录的正调控、质膜及酶结合等生物学过程。KEGG通路富集分析得到60条信号通路，涉及神经活性配体-受体相互作用、5-羟色胺能突触及胰岛素抵抗等相关通路。分子对接结果显示竹叶椒挥发油中芝麻素、胆甾烯基豆蔻酸酯和（-）-β-花柏烯等活性成分与核心靶点具有较好的亲和能力。结论 竹叶椒挥发油中多种活性成分能够作用于PTGS2、CHRM3、PPARA等靶点，并通过多通路发挥抗炎、镇痛作用。

Objective To explore the anti-inflammatory and analgesic active ingredients and mechanism of volatile oil of Zanthoxylum armatum. Methods The constituents in volatile oil of Z. armatum were characterized qualitatively by gas chromatography-mass spectrometry (GC-MS). Targets related to active ingredients were collected by traditional Chinese medicine systems pharmacology (TCMSP), PubChem, Swiss Target Prediction, and Uniprot. Targets related to inflammatory and pain were screened by GisGeNET and OMIM database, "compound-target-disease" network was established by Cytoscape software. Protein-protein interaction (PPI) network was established and tissue distribution of targets were analyzed by BioGPS and SRTRING database. Gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis of targets were carried out by DAVID database. Molecular docking method was applied to verify the interaction between main active ingredients of volatile oil of Z. armatum and relevant core targets. Results A total of 44 compounds were identified in volatile oil of Z. armatum, 78 related targets including prostaglandin-endoperoxide synthase 2 (PTGS2), muscarinic acetylcholine receptor M3 (CHRM3), peroxisome proliferator activated receptor α (PPARA), and cannabinoid receptor 2 (CNR2) were predicted. GO function enrichment analysis revealed that selected targets mainly involved in positive regulation of transcription from RNA polymerase II promoter, plasma membrane, enzyme binding and other biological processes; Sixty signal pathways were screened by KEGG pathway enrichment analysis, including neuroactive ligand-receptor interaction, serotonergic synapse and insulin resistance. Molecular docking indicated that sesamin, cholesterol myristate, and (−)-β-chamigrene had a certain affinity with key targets. Conclusion The active ingredients in volatile oil of Z. armatum regulate multiple signaling pathways to ameliorate inflammation and pain through PTGS2, CHRM3, and PPARA.

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国家自然科学基金资助项目（81274168）；国家自然科学基金资助项目（81573563）；四川省重点研发项目（20ZDYF3291）；中央高校科研业务费专项（2020NZD06）；四川省中医药管理局花椒专项项目（2018HJZX014）