Characterizing the effects of Eugenol on neuronal ionic currents and hyperexcitability
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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 Ca2+ 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.
KeywordsEugenol Na+ current Ca2+ current K+ current Action potential Neuron
This research project was funded by the National Science Council (NSC-98-2320-B-006-027-MY3 and NSC-98-2314-B-006-042-MY2) and the Program for Promoting Academic Excellence and Developing World Class Research Centers, Ministry of Education, Taiwan. This work was also supported in part by a grant from Buddhist Dalin Tzu-Chi General Hospital (DTCRD98-08), Chiayi County, Taiwan. The authors are grateful to Dr. Dong Chun Wu (Department of Neurology, University of British Columbia, Canada) for his critical comments on the manuscript.
Conflicts of interest
None of the authors in this study have any potential conflict of interest or financial interests to disclose.
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