Post-Graduation Program in Pharmacology, Federal University of Santa Maria, Santa Maria, RS, Brazil.
Pharmacy Graduation Course, Federal University of Santa Maria, Santa Maria, RS, Brazil.
Toxicol Appl Pharmacol. 2019 Jul 15;375:64-80. doi: 10.1016/j.taap.2019.05.003. Epub 2019 May 8.
Nectandra grandiflora Ness (Lauraceae) essential oil (EO) main constituent, the sesquiterpenoid (+)-dehydrofukinone (DHF), has sedative and anticonvulsant effects through GABAergic mechanisms. Other DHF-related sesquiterpenoids have been identified in the EO, such as, dehydrofukinone epoxide (DFX), eremophil-11-en-10-ol (ERM) and selin-11-en-4-α-ol (SEL). However, the neuronal effects of these compounds in mammals remain unknown. Therefore, the aim of this study was to evaluate the anxiolytic potential of the N. grandiflora EO and the isolated compounds in in mice. For this purpose, mice were administered orally with vehicle, 10, 30 or 100 mg/kg EO, DHF, DFX, ERM or SEL or 1 mg/kg diazepam. Locomotion and ethological parameters in the open field (OF) and elevated plus maze (EPM) were recorded. We also examined the effect of DFX, ERM and SEL on the membrane potential and calcium influx in synaptosomes, and the presence of the compounds in the cortical tissue using gas chromatography. EOs and isolated compounds reduced anxiety-related parameters in the EPM (open arms time and entries, end activity, head dipping) and OF (center time and entries, total rearing, unprotected rearing, sniffing, grooming) without alter ambulation or induce sedation. Flumazenil (2 mg/kg, i.p.) altered the anxiolytic-like effect of all treatments and vanished the DFX, ERM and SEL-induced changes in membrane potential. However, FMZ did not blocked the DFX-, ERM- and SEL-induced inhibition of calcium influx. Therefore, our results suggest that N. grandiflora EO and isolated compounds induced anxiolytic-like effect in mice due to positive modulation of GABAa receptors and/or inhibition of neuronal calcium influx.
大籽楠（樟科）精油的主要成分，倍半萜烯（+）-脱氢佛司酮（DHF），通过 GABA 能机制具有镇静和抗惊厥作用。在精油中还鉴定出其他与 DHF 相关的倍半萜烯，如脱氢佛司酮环氧化物（DFX）、异戊二烯-11-烯-10-醇（ERM）和西罗-11-烯-4-α-醇（SEL）。然而，这些化合物在哺乳动物中的神经效应仍不清楚。因此，本研究旨在评估大籽楠精油及其分离化合物在小鼠中的抗焦虑潜力。为此，小鼠口服给予溶剂、10、30 或 100mg/kg 精油、DHF、DFX、ERM 或 SEL 或 1mg/kg 地西泮。在开阔场（OF）和高架十字迷宫（EPM）中记录运动和行为参数。我们还研究了 DFX、ERM 和 SEL 对突触体膜电位和钙内流的影响，以及使用气相色谱法在皮质组织中检测化合物的存在。精油和分离化合物减少了 EPM（开放臂时间和进入、结束活动、头浸）和 OF（中央时间和进入、总后空翻、无保护后空翻、嗅探、梳理）中的焦虑相关参数，而不改变运动或诱导镇静。氟马西尼（2mg/kg，ip）改变了所有治疗的抗焦虑样作用，并消除了 DFX、ERM 和 SEL 诱导的膜电位变化。然而，FMZ 并没有阻止 DFX、ERM 和 SEL 诱导的钙内流抑制。因此，我们的结果表明，大籽楠精油和分离化合物通过对 GABAa 受体的正性调节和/或抑制神经元钙内流，在小鼠中诱导抗焦虑样作用。
