title: Characterizing the effects of Eugenol on neuronal ionic currents and hyperexcitability.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurology, National Cheng Kung University Hospital, Tainan, Taiwan.
authors.forename: Chin-Wei
authors.initials: CW
authors.lastname: Huang
authors.forename: Julie Chi
authors.initials: JC
authors.lastname: Chow
authors.forename: Jing-Jane
authors.initials: JJ
authors.lastname: Tsai
authors.forename: Sheng-Nan
authors.initials: SN
authors.lastname: Wu
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D051668:Delayed Rectifier Potassium Channels / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005054:Eugenol / Q000008:administration & dosage / Q000494:pharmacology*; D005910:Glioma / Q000378:metabolism; D008297:Male; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010862:Pilocarpine; D051381:Rats; D017207:Rats, Sprague-Dawley; D019782:Riluzole / Q000494:pharmacology; D012640:Seizures / Q000188:drug therapy* / Q000503:physiopathology; D012720:Severity of Illness Index; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism
chemical_list: D020746:Calcium Channels, L-Type; D051668:Delayed Rectifier Potassium Channels; D015222:Sodium Channels; D010862:Pilocarpine; D005054:Eugenol; D019782:Riluzole