Effects of eugenol on the firing of action potentials in NG108-15 neurons (Huang et al. 2011)

 Download zip file 
Help downloading and running models
Accession:143253
"Rationale: 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. Objectives: 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 INa in the neurons. It not only increased the degree of INa inactivation, but specifically suppressed the non-inactivating INa (INa(NI)). ... 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. ... Conclusion: The synergistic blocking effects of INa and INa(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."
Reference:
1 . Huang CW, Chow JC, Tsai JJ, Wu SN (2012) Characterizing the effects of Eugenol on neuronal ionic currents and hyperexcitability. Psychopharmacology (Berl) 221:575-587 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Channel/Receptor;
Brain Region(s)/Organism:
Cell Type(s): Neuroblastoma;
Channel(s): I Na,p; I Na,t; I Sodium; ATP-senstive potassium current;
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: XPP;
Model Concept(s): Ion Channel Kinetics; Simplified Models; Action Potentials;
Implementer(s): Wu, Sheng-Nan [snwu at mail.ncku.edu.tw]; Huang, Chin-Wei;
Search NeuronDB for information about:  I Na,p; I Na,t; I Sodium; ATP-senstive potassium current;
  
/
EUG_sim
Readme.html
EUG_Psychopharmacology.pdf
EUG_simu.JPG
Neuron_EUG01.ode
                            

Huang CW, Chow JC, Tsai JJ, Wu SN (2012) Characterizing the effects of Eugenol on neuronal ionic currents and hyperexcitability. Psychopharmacology (Berl) 221:575-587[PubMed]

References and models cited by this paper

References and models that cite this paper

Ardjmand A, Fathollahi Y, Sayyah M, Kamalinejad M, Omrani A (2006) Eugenol depresses synaptic transmission but does not prevent the induction of long-term potentiation in the CA1 region of rat hippocampal slices. Phytomedicine 13:146-51 [PubMed]

Benarroch EE (2010) Neuronal voltage-gated calcium channels: brief overview of their function and clinical implications in neurology. Neurology 74:1310-5 [PubMed]

Bender IB (2000) Pulpal pain diagnosis--a review. J Endod 26:175-9 [PubMed]

Black JA, Liu S, Tanaka M, Cummins TR, Waxman SG (2004) Changes in the expression of tetrodotoxin-sensitive sodium channels within dorsal root ganglia neurons in inflammatory pain. Pain 108:237-47 [PubMed]

Chen BS, Peng H, Wu SN (2009) Dexmedetomidine, an alpha2-adrenergic agonist, inhibits neuronal delayed-rectifier potassium current and sodium current. Br J Anaesth 103:244-54

Chen S, Su H, Yue C, Remy S, Royeck M, Sochivko D, Opitz T, Beck H, Yaari Y (2011) An increase in persistent sodium current contributes to intrinsic neuronal bursting after status epilepticus. J Neurophysiol 105:117-29 [PubMed]

Chen SJ, Huang YC, Bn WU, Chen IJ (1997) Eugenolol: an eugenolderived fl946;-adrenoceptor blocker with partial fl946;2-agonist and calcium mobilization inhibition associated vasorelaxant activities Drug Dev Res 40:239-250

Cho JS, Kim TH, Lim JM, Song JH (2008) Effects of eugenol on Na+ currents in rat dorsal root ganglion neurons. Brain Res 1243:53-62 [PubMed]

Chung G, Rhee JN, Jung SJ, Kim JS, Oh SB (2008) Modulation of CaV2.3 calcium channel currents by eugenol. J Dent Res 87:137-41 [PubMed]

Cifelli P, Grace AA (2011) Pilocarpine-induced temporal lobe epilepsy in the rat is associated with increased dopamine neuron activity. Int J Neuropsychopharmacol 103:1-8

Coetzee WA, Amarillo Y, Chiu J, Chow A, Lau D, McCormack T, Moreno H, Nadal MS, Ozaita A, Pou (1999) Molecular diversity of K+ channels. Ann N Y Acad Sci 868:233-85 [PubMed]

Dallmeier K, Carlini EA (1981) Anesthetic, hypothermic, myorelaxant and anticonvulsant effects of synthetic eugenol derivatives and natural analogues. Pharmacology 22:113-27 [PubMed]

Dallmeier Zelger KR, Zelger JL, Carlini EA (1983) New anticonvulsants derived from 4-allyl-2-methoxyphenol (Eugenol): comparison with common antiepileptics in mice. Pharmacology 27:40-9 [PubMed]

Damiani CE, Moreira CM, Zhang HT, Creazzo TL, Vassallo DV (2004) Effects of eugenol, an essential oil, on the mechanical and electrical activities of cardiac muscle. J Cardiovasc Pharmacol 44:688-95 [PubMed]

Damiani CE, Rossoni LV, Vassallo DV (2003) Vasorelaxant effects of eugenol on rat thoracic aorta. Vascul Pharmacol 40:59-66 [PubMed]

Djouhri L, Newton R, Levinson SR, Berry CM, Carruthers B, Lawson SN (2003) Sensory and electrophysiological properties of guinea-pig sensory neurones expressing Nav 1.7 (PN1) Na+ channel alpha subunit protein. J Physiol 546:565-76 [PubMed]

Duarte FS, Gavioli EC, Duzzioni M, Hoeller AA, Canteras NS, De Lima TC (2010) Short- and long-term anxiogenic effects induced by a single injection of subconvulsant doses of pilocarpine in rats: investigation of the putative role of hippocampal pathways. Psychopharmacology (Berl) 212:653-61 [PubMed]

Earl DE, Tietz EI (2011) Inhibition of recombinant L-type voltage-gated calcium channels by positive allosteric modulators of GABAA receptors. J Pharmacol Exp Ther 337:301-11 [PubMed]

Freire CM, Marques MO, Costa M (2006) Effects of seasonal variation on the central nervous system activity of Ocimum gratissimum L. essential oil. J Ethnopharmacol 105:161-6

He YL, Zhan XQ, Yang G, Sun J, Mei YA (2010) Amoxapine inhibits the delayed rectifier outward K+ current in mouse cortical neurons via cAMP-protein kinase A pathways. J Pharmacol Exp Ther 332:437-45 [PubMed]

Huang CW, Cheng JT, Tsai JJ, Wu SN, Huang CC (2009) Diabetic Hyperglycemia Aggravates Seizures and Status Epilepticus-induced Hippocampal Damage. Neurotox Res 15:71-81 [Journal] [PubMed]

   Contribution of ATP-sensitive potassium channels in the neuronal network (Huang et al. 2009) [Model]

Huang CW, Huang CC, Lin MW, Tsai JJ, Wu SN (2008) The synergistic inhibitory actions of oxcarbazepine on voltage-gated sodium and potassium currents in differentiated NG108-15 neuronal cells and model neurons. Int J Neuropsychopharmacol 11:597-610 [Journal] [PubMed]

   Synergistic inhibitory action of oxcarbazepine on INa and IK (Huang et al. 2008) [Model]

Huang CW, Wu SN, Cheng JT, Tsai JJ, Huang CC (2010) Diazoxide reduces status epilepticus neuron damage in diabetes. Neurotox Res 17:305-16 [PubMed]

Huang CW, Wu YJ, Wu SN (2011) Modification of activation kinetics of delayed rectifier K+ currents and neuronal excitability by methyl-β-cyclodextrin. Neuroscience 176:431-41

Huang YC, Wu BN, Lin YT, Chen SJ, Chiu CC, Cheng CJ, Chen IJ (1999) Eugenodilol: a third-generation beta-adrenoceptor blocker, derived from eugenol, with alpha-adrenoceptor blocking and beta2-adrenoceptor agonist-associated vasorelaxant activities. J Cardiovasc Pharmacol 34:10-20

Irie Y, Keung WM (2003) Rhizoma acori graminei and its active principles protect PC-12 cells from the toxic effect of amyloid-beta peptide. Brain Res 963:282-9

Köseoğlu BG, Tanrikulu S, Subay RK, Sencer S (2006) Anesthesia following overfilling of a root canal sealer into the mandibular canal: a case report. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 101:803-6 [PubMed]

Kawaguchi A, Asano H, Matsushima K, Wada T, Yoshida S, Ichida S (2007) Enhancement of sodium current in NG108-15 cells during neural differentiation is mainly due to an increase in NaV1.7 expression. Neurochem Res 32:1469-75 [PubMed]

Lin MW, Wang YJ, Liu SI, Lin AA, Lo YC, Wu SN (2008) Characterization of aconitine-induced block of delayed rectifier K(+) current in differentiated NG108-15 neuronal cells. Neuropharmacology [Journal] [PubMed]

   Properties of aconitine-induced block of KDR current in NG108-15 neurons (Lin et al. 2008) [Model]

Lin MW, Yang SR, Huang MH, Wu SN (2004) Stimulatory actions of caffeic acid phenethyl ester, a known inhibitor of NF-kappaB activation, on Ca2+-activated K+ current in pituitary GH3 cells. J Biol Chem 279:26885-92 [PubMed]

Lionnet L, Beaudry F, Vachon P (2010) Intrathecal eugenol administration alleviates neuropathic pain in male Sprague-Dawley rats. Phytother Res 24:1645-53 [PubMed]

Lossin C, Wang DW, Rhodes TH, Vanoye CG, George AL (2002) Molecular basis of an inherited epilepsy. Neuron 34:877-84 [PubMed]

Mathew SJ, Murrough JW, aan het Rot M, Collins KA, Reich DL, Charney DS (2010) Riluzole for relapse prevention following intravenous ketamine in treatment-resistant depression: a pilot randomized, placebo-controlled continuation trial. Int J Neuropsychopharmacol 13:71-82 [PubMed]

Meves H, Schwarz JR, Wulfsen I (1999) Separation of M-like current and ERG current in NG108-15 cells. Br J Pharmacol 127:1213-23 [PubMed]

Muller M, Pape HC, Speckmann EJ, Gorji A (2006) Effect of eugenol on spreading depression and epileptiform discharges in rat neocortical and hippocampal tissues. Neuroscience 140:743-51 [PubMed]

Ni Y, Zhao X, Bao G, Zou L, Teng L, Wang Z, Song M, Xiong J, Bai Y, Pei G (2006) Activation of beta2-adrenergic receptor stimulates gamma-secretase activity and accelerates amyloid plaque formation. Nat Med 12:1390-6

Ohkubo T, Kitamura K (1997) Eugenol activates Ca(2+)-permeable currents in rat dorsal root ganglion cells. J Dent Res 76:1737-44 [PubMed]

Park CK, Kim K, Jung SJ, Kim MJ, Ahn DK, Hong SD, Kim JS, Oh SB (2009) Molecular mechanism for local anesthetic action of eugenol in the rat trigeminal system. Pain 144:84-94 [PubMed]

Pena F, Tapia R (2000) Seizures and neurodegeneration induced by 4-aminopyridine in rat hippocampus in vivo: role of glutamate- and GABA-mediated neurotransmission and of ion channels. Neuroscience 101:547-61 [PubMed]

Pinsky PF, Rinzel J (1994) Intrinsic and network rhythmogenesis in a reduced Traub model for CA3 neurons. J Comput Neurosci 1:39-60 [Journal] [PubMed]

   CA3 pyramidal cell: rhythmogenesis in a reduced Traub model (Pinsky, Rinzel 1994) [Model]

Pitkanen A, Schwartzkroin PA, Moshe SL (2006) Models of seizures and epilepsy

Pourgholami MH, Kamalinejad M, Javadi M, Majzoob S, Sayyah M (1999) Evaluation of the anticonvulsant activity of the essential oil of Eugenia caryophyllata in male mice. J Ethnopharmacol 64:167-71 [PubMed]

Racine RJ, Burnham WM, Gartner JG, Levitan D (1973) Rates of motor seizure development in rats subjected to electrical brain stimulation: strain and inter-stimulation interval effects. Electroencephalogr Clin Neurophysiol 35:553-6 [PubMed]

Sayyah M, Valizadeh J, Kamalinejad M (2002) Anticonvulsant activity of the leaf essential oil of Laurus nobilis against pentylenetetrazole- and maximal electroshock-induced seizures. Phytomedicine 9:212-6 [PubMed]

Segal MM (2002) Sodium channels and epilepsy electrophysiology. Novartis Found Symp 241:173-80; discussion 180-8, 226-32 [PubMed]

Segal MM, Douglas AF (1997) Late sodium channel openings underlying epileptiform activity are preferentially diminished by the anticonvulsant phenytoin. J Neurophysiol 77:3021-34 [Journal] [PubMed]

Sensch O, Vierling W, Brandt W, Reiter M (2000) Effects of inhibition of calcium and potassium currents in guinea-pig cardiac contraction: comparison of beta-caryophyllene oxide, eugenol, and nifedipine. Br J Pharmacol 131:1089-96

Stafstrom CE (2007) Persistent sodium current and its role in epilepsy. Epilepsy Curr 7:15-22 [PubMed]

Tsai TY, Tsai YC, Wu SN, Liu YC (2006) Tramadol-induced blockade of delayed rectifier potassium current in NG108-15 neuronal cells. Eur J Pain 10:597-601 [PubMed]

Urbani A, Belluzzi O (2000) Riluzole inhibits the persistent sodium current in mammalian CNS neurons. Eur J Neurosci 12:3567-74 [PubMed]

Warren CA, Mok L, Gordon S, Fouad AF, Gold MS (2008) Quantification of neural protein in extirpated tooth pulp. J Endod 34:7-10 [PubMed]

Wie MB, Won MH, Lee KH, Shin JH, Lee JC, Suh HW, Song DK, Kim YH (1997) Eugenol protects neuronal cells from excitotoxic and oxidative injury in primary cortical cultures. Neurosci Lett 225:93-6 [PubMed]

Won MH, Lee JC, Kim YH, Song DK, Suh HW, Oh YS, Kim JH, Shin TK, Lee YJ, Wie MB (1998) Postischemic hypothermia induced by eugenol protects hippocampal neurons from global ischemia in gerbils. Neurosci Lett 254:101-4 [PubMed]

Wu BN, Shen KP, Lin RJ, Huang YC, Chiang LC, Lo YC, Lin CY, Chen IJ (2000) Lipid solubility of vasodilatory vanilloid-type beta-blockers on the functional and binding activities of beta-adrenoceptor subtypes. Gen Pharmacol 34:321-8

Wu SN, Chen BS, Hsu TI, Peng H, Wu YH, Lo YC (2009) Analytical studies of rapidly inactivating and noninactivating sodium currents in differentiated NG108-15 neuronal cells. J Theor Biol 259:828-36 [PubMed]

Wu SN, Chen BS, Wu YH, Peng H, Chen LT (2009) The mechanism of the actions of oxaliplatin on ion currents and action potentials in differentiated NG108-15 neuronal cells. Neurotoxicology 30:677-85 [PubMed]

Wu SN, Li HF, Jan CR (1998) Regulation of Ca2+-activated nonselective cationic currents in rat pituitary GH3 cells: involvement in L-type Ca2+ current. Brain Res 812:133-41 [PubMed]

Wu SN, Lo YK, Chen H, Li HF, Chiang HT (2001) Rutaecarpine-induced block of delayed rectifier K+ current in NG108-15 neuronal cells. Neuropharmacology 41:834-43 [PubMed]

Wu SN, Wu YH, Chen BS, Lo YC, Liu YC (2009) Underlying mechanism of actions of tefluthrin, a pyrethroid insecticide, on voltage-gated ion currents and on action currents in pituitary tumor (GH3) cells and GnRH-secreting (GT1-7) neurons. Toxicology 258:70-7 [PubMed]

Yang BH, Piao ZG, Kim YB, Lee CH, Lee JK, Park K, Kim JS, Oh SB (2003) Activation of vanilloid receptor 1 (VR1) by eugenol. J Dent Res 82:781-5 [PubMed]

Zgrajka W, Nieoczym D, Czuczwar M, Kiś J, Brzana W, Wlaź P, Turski WA (2010) Evidences for pharmacokinetic interaction of riluzole and topiramate with pilocarpine in pilocarpine-induced seizures in rats. Epilepsy Res 88:269-74 [PubMed]

(61 refs)