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《工程(英文)》 >> 2020年 第6卷 第5期 doi: 10.1016/j.eng.2019.07.027

单萜类化合物芳樟醇、甲基丁香酚、草蒿脑和香茅醛对配体门控离子通道的作用模式

a College of Natural and Computational Sciences, Hawaii Pacific University, Kaneohe, HI 96744, USA

b Department of Molecular Biosciences and Bioengineering, University of Hawaii at Manoa, Honolulu, HI 96822, USA

c Department of Internal Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA

收稿日期: 2019-01-16 修回日期: 2019-07-15 录用日期: 2019-07-23 发布日期: 2020-03-07

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摘要

在传统的医学治疗中,精油被用作镇静剂、抗惊厥剂以及局部麻醉剂,还可以用作储藏食品、水果、蔬菜和谷物等的防腐剂,同时,它还能用作食品生产的生物农药。芳樟醇(LL)以及其他一些主要组分,如甲基丁香酚(ME)、草蒿脑(EG)和香茅醛是许多精油(如罗勒精油)中的活性化学成分。罗勒精油以及上述单萜类化合物在驱除害虫等方面有明显的功效。然而,这些化学成分的作用机制尚不明确。众所周知,γ-氨基丁酸A型受体(GABAAR)和烟碱型乙酰胆碱受体(nAChR)是目前市场上使用的合成杀虫剂的主要分子靶标。此外,GABAAR靶向治疗也已经有了数十年的临床应用实践,如巴比妥类药物和苯二氮类药物。在本研究中,我们研究了LL、ME、EG和香茅醛对GABAAR和nAChR的电生理作用,以进一步了解它们作为传统药物治疗剂和杀虫剂的多功能性。研究结果表明,LL对GABAAR和nAChR均有抑制作用,这或许可以解释LL的杀虫活性。LL是GABAAR的一种浓度依赖性、非竞争性抑制剂,因为在实验中我们发现,小鼠α1β3γ2L GABAAR的γ-氨基丁酸(GABA)半最大效应浓度(EC50)值不受LL影响:在LL不存在或存在5 mmol·L–1 LL的情况下,该半最大效应浓度值分别为(36.2 ± 7.9) μmol·L–1以及(36.1 ± 23.8) μmol·L–1。LL对GABAAR的半抑制浓度(IC50)约为3.2 mmol·L–1。考虑到在精油之中存在着多种单萜类化合物,所以LL可能与此前被表征为GABAAR激动剂和正变构调节物的ME以及其他单萜类化合物具有协同作用,这为LL的镇静、抗惊厥效用和杀虫活性提供了一种可能的解释。

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