抗金黄色葡萄球菌复方精油的药效物质与初步作用机制

Pharmacological substances and preliminary action mechanism of compound essential oil against Staphylococcus aureus

关键词:  复方精油, 抗金黄色葡萄球菌, 药效物质基础, 作用机制

Key words:  compound essential oil, against Staphylococcus aureus, pharmacodynamic, action mechanism

摘要:

为阐明抗金黄色葡萄球菌复方精油的药效物质基础及其作用机制,该研究采用水蒸气蒸馏法制备艾草、留兰香、牛至单方精油及两种复方精油(复方精油1、复方精油2),利用气相色谱-质谱联用技术分析抗金黄色葡萄球菌精油的活性成分,采用滤纸片扩散法评价各精油对金黄色葡萄球菌的抑菌活性,综合运用网络药理学和分子对接模拟技术,探究活性最强复方精油(复方精油2)的潜在抗菌作用机制。结果表明:(1)复方精油2含有41种化学成分,其主要活性成分包括百里香酚(29.33%)、香芹酚(9.13%)等。(2)单方精油和复方精油的抑菌活性强弱顺序为复方精油2 [(40.18±1.67)mm]> 牛至精油 [(38.64±1.47)mm]> 复方精油1 [(24.87±0.85)mm]> 艾草精油 [(13.12±0.56)mm]> 留兰香精油 [(11.28±0.75)mm],复方精油2抗金黄色葡萄球菌作用最强。(3)复方精油2可通过多靶点协同作用抑制金黄色葡萄球菌,调控SRC、MAPK3等核心靶点,并影响中性粒细胞胞外诱捕网形成和表皮生长因子受体酪氨酸激酶抑制剂耐药性等信号通路。多种活性成分与核心靶点具有良好的结合能。综上认为,复方精油2是一种有效的抗金黄色葡萄球菌植物源抗菌剂,其独特的化学成分及多靶点、多通路协同作用机制,为其作为天然抗菌剂的深入开发应用提供了重要依据。

Abstract:

In order to elucidate the pharmacodynamic material basis and mechanisms of underlying the anti-bacterial efficacy of compound essential oils against Staphylococcus aureus, this study employed steam distillation method to prepare single essential oils of Artemisia argyi, Mentha spicata and Origanum vulgare, and two compound essential oils(Compound essential oil 1 and Compound essential oil 2); gas chromatography-mass spectrometry(GC-MS)analysis was performed to identify the active constituents of the essential oils exhibiting anti-Staphylococcus aureus activity; the filter paper diffusion method assay was utilized to evaluate the anti-bacterial activity of each essential oil against Staphylococcus aureus; network pharmacology and molecular docking simulations were integrated to investigate the potential anti-bacterial mechanism of the most bioactive compound essential oil(Compound essential oil 2). The results were as follows:(1)Compound essential oil 2 comprised 41 chemical constituents, with its primary bioactive components including thymol(29.33%)and carvacrol(9.13%).(2)The order of anti-bacterial efficacy among single and compound essential oils was Compound essential oil 2 [(40.18±1.67)mm] > Origano vulgare essential oil [(38.64 ± 1.47)mm] > Compound essential oil 1 [(24.87±0.85)mm] > Artemisia argyi essential oil [(13.12 ± 0.56)mm] > Mentha spicata essential oil [(11.28 ± 0.75)mm]. Compound essential oil 2 exhibited the strongest inhibitory effect against Staphylococcus aureus.(3)Compound essential oil 2 exerted inhibition of Staphylococcus aureus through multi-target synergistic effects, modulating core protein targets including SRC and MAPK3, and regulating signaling pathways of notably neutrophil extracellular trap formation, drug resistance of epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)and so on. Several bioactive components showed favorable binding energies with core targets. These collective findings demonstrate that Compound essential oil 2 is a novel plant-derived anti-Staphylococcus aureus candidate, and its unique chemical constituents, multi-target and multi-pathway synergistic mechanism provide important basis for the in-depth development and application as a natural anti-bacterial agent.