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
Amy S. Li , Akimasa Iijima , Junhao Huang , Qing X. Li , Yongli Chen
工程(英文) ›› 2020, Vol. 6 ›› Issue (5) : 541 -545.
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
Putative Mode of Action of the Monoterpenoids Linalool, Methyl Eugenol, Estragole, and Citronellal on Ligand-Gated Ion Channels
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。
Essential oil has been used as sedatives, anticonvulsants, and local anesthetics in traditional medical remedies; as preservatives for food, fruit, vegetable, and grain storage; and as bio-pesticides for food production. Linalool (LL), along with a few other major components such as methyl eugenol (ME), estragole (EG), and citronellal, are the active chemicals in many essential oils such as basil oil. Basil oil and the aforementioned monoterpenoids are potent against insect pests. However, the molecular mechanism of action of these chemical constituents is not well understood. It is well-known that the γ-aminobutyric acid type A receptors (GABAARs) and nicotinic acetylcholine receptor (nAChR) are primary molecular targets of the synthetic insecticides used in the market today. Furthermore, GABAAR-targeted therapeutics have been used in clinics for many decades, including barbiturates and benzodiazepines, to name just a few. In this research, we studied the electrophysiological effects of LL, ME, EG, and citronellal on GABAAR and nAChR to further understand their versatility as therapeutic agents in traditional remedies and as insecticides. Our results revealed that LL inhibits both GABAAR and nAChR, which may explain its insecticidal activity. LL is a concentration-dependent, non-competitive inhibitor on GABAAR, as the half-maximal effective concentration values of γ-aminobutyric acid (GABA) for the rat α1β3γ2L GABAAR were not affected by LL: (36.2 ± 7.9) µmol·L−1 and (36.1 ± 23.8) µmol·L−1 in the absence and presence of 5 mmol·L−1 LL, respectively. The half-maximal inhibitory concentration (IC50) of LL on GABAAR was approximately 3.2 mmol·L−1. Considering that multiple monoterpenoids are found within the same essential oil, it is likely that LL has a synergistic effect with ME, which has been previously characterized as both a GABAAR agonist and a positive allosteric modulator, and with other monoterpenoids, which offers a possible explanation for the sedative and anticonvulsant effects and the insecticidal activities of LL.
精油 / γ-氨基丁酸A型受体 / 芳樟醇 / 单萜 / 烟碱型乙酰胆碱受体
Essential oil / γ-aminobutyric acid type A receptor / Linalool / Monoterpenoid / Nicotinic acetylcholine receptor
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