基于网络药理学揭示复合植物精油药理活性及作用机制

doi:10.16431/j.cnki.1671-7236.2023.05.040

摘要/Abstract

摘要： 【目的】基于网络药理学技术探究复合植物精油(牛至精油、肉桂醛、桉叶油)的药理活性及整体作用机制。【方法】利用中药系统药理学分析数据库(TCMSP)获得复合植物精油活性成分的潜在作用靶点,利用Cytoscape 3.7.1软件构建成分-靶点网络图,通过STRING平台构建蛋白相互作用(PPI)网络图并进行可视化分析,使用DAVID数据库对靶点进行GO功能和KEGG通路富集分析,并利用AutoDock Vina软件对主要活性成分和关键靶点进行分子对接分析。【结果】复合植物精油的8个活性成分可作用于白细胞介素6(interleukin 6,IL6)、人前列腺素内过氧化物合酶2(prostaglandin-endoperoxide synthase 2,PTGS2)、Toll样受体4(Toll-like receptors 4,TLR4)、转录因子p65(transcription factor p65,RELA)、内皮型一氧化氮合酶(nitric-oxide synthase,endothelial,NOS3)、芳香烃受体蛋白(aryl hydrocarbon receptor,AHR)、细胞色素P450 1A1(cytochrome P450 1A1,CYP1A1)、人NF-κB抑制剂(NF-kappa-B inhibitor alpha,NFKBIA)、γ-氨基丁酸受体亚基α-2(gamma-aminobutyric-acid receptor alpha-2 subunit,GABRA2)等关键靶点。GO功能富集分析显示,共获得269个条目,其中与生物过程相关的条目181个,涉及腺苷酸环化酶激活肾上腺素能受体信号通路、突触后膜电位调节等;与细胞组分相关的条目29个,涉及质膜的组成、神经元投射等;与分子功能相关的条目59个,涉及激活神经递质受体活性、调节细胞外配体门控离子通道活性等。共有KEGG信号通路72条,主要参与调控神经活性配体-受体相互作用、脂质和动脉粥样硬化、cGMP-PKG信号通路、钙信号通路、TLR信号通路、Th17细胞分化等信号通路,同时与酒精性肝病、卡波西肉瘤相关性疱疹病毒感染等疾病相关。分子对接结果显示,丁香酚、石竹烯、百里香酚与IL6、PTGS2结合紧密,亲和力较好。【结论】复合植物精油可通过丁香酚、石竹烯、百里香酚、D-柠檬烯、肉桂醛等多种活性成分作用于IL6、PTGS2、TLR4、RELA等靶点上,参与调控神经、免疫调节、抑菌、抗炎和抗肿瘤等相关信号通路,具有多成分、多靶点、多通路的作用机制。

关键词: 牛至精油; 肉桂醛; 桉叶油; 网络药理学

Abstract: 【Objective】 The purpose of this experiment was to explore the pharmacological activity and overall mechanism of compound plant essential oils (oregano essential oil,cinnamaldehyde,Eucalyptus oil) based on network pharmacology.【Method】 The targets of compound plant essential oils were screened using TCMSP database.The drug-ingredient-target network was constructed by Cytoscape 3.7.1 software,and PPI network was constructed by STRING and visualization.The targets were annotated by GO function and KEGG pathway enrichment analysis through DAVID database.And AutoDock Vina software was used for molecular docking of selected active components and key targets.【Result】 Compound plant essential oils acted on the key targets including interleukin 6 (IL6),prostaglandin-endoperoxide synthase 2 (PTGS2),Toll-like receptors 4 (TLR4),transcription factor p65 (RELA),nitric-oxide synthase,endothelial (NOS3),aryl hydrocarbon receptor (AHR),cytochrome P450 1A1 (CYP1A1),NF-kappa-B inhibitor alpha (NFKBIA),gamma-aminobutyric-acid receptor alpha-2 subunit (GABRA2) and so on with 8 active ingredients.The GO function enrichment analysis showed that 269 items were obtained,181 items were related to biological processes,involving adenylate cyclase-activating adrenergic receptor signaling pathway,regulation of postsynaptic membrane potential,etc.,59 items related to cell components,involving integral component of plasma membrane,neuron projection,etc..29 items related to molecular functions,involving neurotransmitter receptor activity,excitatory extracellular ligand-gated ion channel activity,etc..KEGG pathway analysis showed that 72 items related to signal pathways,and participated in the regulation of neuroactive ligand-receptor interaction,lipid and atherosclerosis,cGMP-PK signaling pathway,calcium signaling pathway,TLR signaling pathway,Th17 cell differentiation,etc..It was also associated with alcoholic liver disease,Kaposi sarcoma-associated Herpesvirus infection and other diseases.The results of molecular docking showed that the core components such as eugenol,caryophyllene,thymol were closely bound to the key targets such as IL6 and PTGS2,and had good affinity.【Conclusion】 The compound plant essential oils might act on key targets such as eugenol,caryophyllene,thymol,D-limonene,cinnamaldehyde and other active ingredients,played an important role mainly through regulating of nerves and immune systems,anti-bacterial,anti-inflammatory and anti-tumor signaling pathways acting on IL6,PTGS2,TLR4,RELA and other key targets.The compound plant essential oils had a multi-component,multi-target,multi-pathway action mechanism.

Key words: oregano essential oil; cinnamaldehyde; Eucalyptus oil; network pharmacology

中图分类号:

S859.7

胡湘云, 易显凤, 黄志朝, 吴思谦, 陈政谕, 吕玲燕, 黄超, 粟永春. 基于网络药理学揭示复合植物精油药理活性及作用机制[J]. 中国畜牧兽医, 2023, 50(5): 2139-2148.

HU Xiangyun, YI Xianfeng, HUANG Zhichao, WU Siqian, CHEN Zhengyu, LYU Lingyan, Huang Chao, SU Yongchun. Pharmacological Activity and Action Mechanism of Compound Plant Essential Oils Revealed Based on Network Pharmacology[J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(5): 2139-2148.

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