Department of Neurology, National Cheng Kung University Hospital, Tainan, Taiwan.
Psychopharmacology (Berl). 2012 Jun;221(4):575-87. doi: 10.1007/s00213-011-2603-y. Epub 2011 Dec 13.
Eugenol (EUG, 4-allyl-2-methoxyphenol), the main component of essential oil extracted from cloves, has various uses in medicine because of its potential to modulate neuronal excitability. However, its effects on the ionic mechanisms remains incompletely understood.
We aimed to investigate EUG's effects on neuronal ionic currents and excitability, especially on voltage-gated ion currents, and to verify the effects on a hyperexcitability-temporal lobe seizure model.
With the aid of patch-clamp technology, we first investigated the effects of EUG on ionic currents in NG108-15 neuronal cells differentiated with cyclic AMP. We then used modified Pinsky-Rinzel simulation modeling to evaluate its effects on spontaneous action potentials (APs). Finally, we investigated its effects on pilocarpine-induced seizures in rats.
EUG depressed the transient and late components of I(Na) in the neurons. It not only increased the degree of I(Na) inactivation, but specifically suppressed the non-inactivating I(Na) (I(Na(NI))). Its inhibition of I (Na(NI)) was reversed by tefluthrin. In addition, EUG diminished L-type Ca(2+) current and delayed rectifier K(+) current only at higher concentrations. EUG's effects on APs frequency reduction was verified by the simulation modeling. In pilocarpine-induced seizures, the EUG-treated rats showed no shorter seizure latency but a lower seizure severity and mortality than the control rats. The EUG's effect on seizure severity was occluded by the I(Na(NI)) antagonist riluzole.
The synergistic blocking effects of I (Na) and I(Na(NI)) contributes to the main mechanism through which EUG affects the firing of neuronal APs and modulate neuronal hyperexcitability such as pilocarpine-induced temporal lobe seizures.
丁香精油中的主要成分丁香酚（EUG，4-丙烯基-2-甲氧基苯酚）由于其调节神经元兴奋性的潜力，在医学上有多种用途。然而，其对离子机制的影响尚不完全清楚。
我们旨在研究 EUG 对神经元离子电流和兴奋性的影响，特别是对电压门控离子电流的影响，并验证其对高兴奋性-颞叶癫痫模型的影响。
借助膜片钳技术，我们首先研究了 EUG 对 cAMP 分化的 NG108-15 神经元细胞中离子电流的影响。然后，我们使用改进的 Pinsky-Rinzel 模拟建模来评估其对自发性动作电位（AP）的影响。最后，我们研究了 EUG 对匹罗卡品诱导的大鼠癫痫发作的影响。
EUG 抑制神经元中的瞬时和晚期 I(Na)。它不仅增加了 I(Na)失活的程度，而且特异性抑制了非失活的 I(Na)（I(Na(NI))）。其对 I(Na(NI))的抑制作用可被七氟烷逆转。此外，EUG 仅在较高浓度下才抑制 L 型 Ca(2+)电流和延迟整流钾电流。模拟建模验证了 EUG 对 AP 频率降低的影响。在匹罗卡品诱导的癫痫发作中，与对照组相比，EUG 治疗组的大鼠潜伏期无明显缩短，但癫痫发作严重程度和死亡率较低。I(Na(NI))拮抗剂利鲁唑阻断了 EUG 对癫痫严重程度的影响。
I(Na)和 I(Na(NI))的协同阻断作用是 EUG 影响神经元 AP 放电并调节神经元过度兴奋（如匹罗卡品诱导的颞叶癫痫）的主要机制。
