Abstract 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, the 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 (EC50) 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.

中文翻译：

---

单萜类芳樟醇、甲基丁香酚、雌二醇和香茅醛对配体门控离子通道的推定作用方式

摘要 精油在传统医学疗法中被用作镇静剂、抗惊厥剂和局部麻醉剂；作为食品、水果、蔬菜和粮食储存的防腐剂；以及作为食品生产的生物农药。芳樟醇 (LL) 以及其他一些主要成分，如甲基丁香酚 (ME)、草蒿脑 (EG) 和香茅醛，是许多精油（如罗勒油）中的活性化学物质。罗勒油和上述单萜类化合物对害虫有效。然而，这些化学成分的分子作用机制尚不清楚。众所周知，γ-氨基丁酸 A 型受体 (GABAARs) 和烟碱乙酰胆碱受体 (nAChR) 是当今市场上使用的合成杀虫剂的主要分子靶点。此外，GABAAR 靶向疗法已在临床上使用了几十年，包括巴比妥类药物和苯二氮卓类药物，仅举几例。在这项研究中，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疗法中的治疗剂和杀虫剂的多功能性。我们的结果表明，LL 抑制 GABAAR 和 nAChR，这可以解释其杀虫活性。LL 是 GABAAR 的浓度依赖性、非竞争性抑制剂，因为 γ-氨基丁酸 (GABA) 对大鼠 α1β3γ2L GABAAR 的半数最大有效浓度 (EC50) 值不受 LL 影响：(36.2 ± 7.9) μmol ·L-1 和 (36.1 ± 23.8) μmol·L-1，分别在 5 mmol·L-1 LL 不存在和存在下。LL对GABAAR的半数最大抑制浓度(IC50)约为3.2 mmol·L-1。考虑到在同一精油中发现了多种单萜类化合物，LL 可能与 ME 具有协同作用，ME 以前被表征为 GABAAR 激动剂和正变构调节剂，以及与其他单萜类化合物，这提供了可能的解释LL 的镇静和抗惊厥作用以及杀虫活性。