Modulation of Neurotransmission by a Specified Oregano Extract Alters Brain Electrical Potentials Indicative of Antidepressant-Like and Neuroprotective Activities

M. Hasan Mohajeri, Regina Goralczyk, Wilfried Dimpfel

DSM Nutritional Products Ltd., R & D Human Nutrition and Health, Basel, Switzerland.
NeuroCode AG, Wetzlar, Germany.

DOI: 10.4236/nm.2012.31006                

Abstract

Different behavioral states are characterized by distinct patterns of global brain activity. Therefore, the biological effects of herbal extracts on brain functions can be assessed by analyzing the local field potentials, the so-called electropharmacogram analysis. Inspired by our recent findings that a specified oregano extract (OE) exhibited a triple-reuptake activity in vitro, this extract was tested in model of Tele-Stereo-electroencephalogram (EEG) to elucidate how OE affects the electrical brain activity in freely moving rats. Furthermore, discriminant analysis was performed to compare the electric brain activity of four standardized brain regions with those produced by several reference compounds, representing a whole variety of clinical indications. Oral intake of OE produced fast and robust dose and time dependent EEG alterations consisting of significant changes of spectral power in comparison to controls. Strongest effects were seen with respect to alpha1, alpha2 and beta1 waves representing an activation of serotonergic, dopaminergic and glutamatergic neurotransmission, respectively. Moreover, the discriminant analysis revealed that OE’s pattern of activity locates in close vicinity to antidepressant and neuroprotective compound. The presented data support the hypothesis suggesting the use of OE as a neuroprotective dietary supplement to promote mood, motivation and mental wellbeing.

Keywords

EEG; Dopamine; Serotonin; Noradrenalin; OréVida; Diet; Mood; Therapy

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	B. S. McEwen, “Physiology and Neurobiology of Stress and Adaptation: Central Role of the Brain,” Physiological Reviews, Vol. 87, No. 3, 2007, pp. 873-904. doi:10.1152/physrev.00041.2006
[2]	R. Cools, K. Nakamura and N. D. Daw, “Serotonin and Dopamine: Unifying Affective, Activational, and Decision Functions,” Neuropsychopharmacology, Vol. 36, No. 1, 2011, pp. 98-113. doi:10.1038/npp.2010.121
[3]	W. C. Drevets, J. L. Price and M. L. Furey, “Brain Structural and Functional Abnormalities in Mood Disorders: Implications for Neurocircuitry Models of Depression,” Brain Structure & Function, Vol. 213, No. 1-2, 2008, pp 93-118. doi:10.1007/s00429-008-0189-x
[4]	A. O. Mechan, A. Fowler, N. Seifert, H. Rieger, T. Wohrle, S. Etheve, A. Wyss, G. Schuler, B. Colletto, C. Kilpert, J. Aston, J. M. Elliott, R. Goralczyk and M. H. Mohajeri, “Monoamine Reuptake Inhibition and Mood-Enhancing Potential of a Specified Oregano Extract,” British Journal of Nutrition, Vol. 105, No. 8, 2011, pp. 1150-1163. doi:10.1017/S0007114510004940
[5]	K. Blum, T. J. Chen, S. Morse, J. Giordano, A. L. Chen, J. Thompson, C. Allen, A. Smolen, J. Lubar, E. Stice, B. W. Downs, R. L. Waite, M. A. Madigan, M. Kerner, F. Fornari and E. R. Braverman, “Overcoming qEEG Abnormalities and Re-ward Gene Deficits during Protracted Abstinence in Male Psychostimulant and Polydrug Abusers Utilizing Putative Dopamine D Agonist Therapy: Part 2,” Postgraduate Medicine, Vol. 122, No. 6, 2010, pp. 214- 226. doi:10.3810/pgm.2010.11.2237
[6]	M. J. Jutras and E. A. Buffalo, “Synchronous Neural Activity and Memory Formation,” Current Opinion in Neurobiology, Vol. 20, No. 2, 2010, pp. 150-155. doi:10.1016/j.conb.2010.02.006
[7]	K. Kitaoka, A. Hattori, S. Chikahisa, K. Miyamoto, Y. Nakaya and H. Sei, “Vitamin A Deficiency Induces a Decrease in EEG Delta Power during Sleep in Mice,” Brain Research, Vol. 1150, 2007, pp. 121-130. doi:10.1016/j.brainres.2007.02.077
[8]	M. Moazami-Goudarzi, J. Sarnthein, L. Michels, R. Moukhtieva and J. Jeanmonod, “Enhanced Frontal Low and High Frequency Power and Synchronization in the Resting EEG of Parkinsonian Patients,” Neuroimage, Vol. 41, No. 3, 2008, pp. 985-997. doi:10.1016/j.neuroimage.2008.03.032
[9]	W. Dimpfel, A. Kler, E. Kriesl, R. Lehnfeld and I. K. Keplinger-Dimpfel, “Source Density Analysis of the Human EEG after Ingestion of a Drink Containing Decaffeinated Extract of Green Tea Enriched with L-Theanine and Theogallin,” Nutritional Neuroscience, Vol. 10, No. 3-4, 2007, pp.169-180. doi:10.1080/03093640701580610
[10]	W. Dimpfel, “Preclinical Data Base of Pharmaco-Specific Rat EEG Fingerprints (Tele-Stereo-EEG),” European Journal of Medical Research, Vol. 8, No. 5, 2003, pp. 199- 207.
[11]	A. Czubak, E. Nowakowska, K. Burda, K. Kus and J. Metelska, “Cognitive Effects of GABAergic Anti-epileptic Drugs,” Arzneimittelforschung, Vol. 60, No. 1, 2010, pp. 1-11. doi:10.1055/s-0031-1296242
[12]	A. G. Malykh and M. R. Sadaie, “Piracetam and Piracetam-Like Drugs: from Basic Science to Novel Clinical Applications to CNS Disorders,” Drugs, Vol. 70, No. 3, 2010, pp. 287-312. doi:10.2165/11319230-000000000-00000
[13]	W. Dimpfel, “Pharmacological Modulation of Cholinergic Brain Activity and Its Reflection in Special EEG Frequency Ranges from Various Brain Areas in the Freely Moving Rat (Tele-Stereo-EEG),” European Neuropsy-chopharmacology, Vol. 15, No. 6, 2005, pp. 673-682. doi:10.1016/j.euroneuro.2005.03.006
[14]	W. Dimpfel and F. Schober, “Norepinephrine, EEG Theta Waves and Sedation,” Pharmacology, Vol. 1, 2001, pp. 89-97.
[15]	W. Dimpfel, “Pharmacological Modulation of Dopaminergic Brain Activity and Its Reflection in Spectral Frequencies of the Rat Electropharmacogram,” Neuropsychobiology, Vol. 58, No. 3-4, 2008, pp. 178-186. doi:10.1159/000191124
[16]	W. Dimpfel, M. Spuler, R. Koch and W. Schatton, “Radioelectroencephalographic Comparison of Memantine with Receptor-Specific Drugs Acting on Dopaminergic Transmission in Freely Moving Rats,” Neuropsychobiology, Vol. 18, No. 18, 1987, pp. 212-218. doi:10.1159/000118420
[17]	S. Ortigue, N. Patel and F. Bianchi-Demicheli, “New Electroencephalogram (EEG) Neuroimaging Methods of Analyzing Brain Activity Applicable to the Study of Human Sexual Response,” The Journal of Sexual Medicine, Vol. 6, No. 7, 2009, pp. 1830-1845. doi:10.1111/j.1743-6109.2009.01271.x
[18]	F. Pulver-muller, Y. Shtyrov and O. Hauk, “Understanding in an Instant: Neurophysiological Evidence for Mechanistic Language Circuits in the Brain,” Brain and Language, Vol. 110, No. 2, 2009, pp. 81-94. doi:10.1016/j.bandl.2008.12.001
[19]	J. M. Schoffelen and J. Gross, “Source Connectivity Analysis with MEG and EEG,” Human Brain Mapping, Vol. 30, No. 6, 2009, pp.1857-1865. doi:10.1002/hbm.20745
[20]	W. Dimpfel, M. Spuler and H. O. Borbe, “Monitoring of the Effects of Antidepressant Drugs in the Freely Moving Rat by Radioelectroencephalography (Tele-Stereo-EEG),” Neurop-sychobiology, Vol. 19, No. 2, 1988, pp. 116-120. doi:10.1159/000118445
[21]	G. S. Ruigt, S. Engelen, A. Gerrits and F. Verbon, “Computer-Based Prediction of Psychotropic Drug Classes Based on a Discriminant Analysis of Drug Effects on Rat Sleep,” Neuropsychobiology, Vol. 28, No. 3, 1993, pp. 138-153. doi:10.1159/000119016
[22]	W. Dimpfel, “Rat Electropharmacograms of the Flavonoids Rutin and Quercetin in Comparison to Those of Moclobemide and Clinically Used Reference Drugs Suggest Antidepressive and/or Neuroprotective Action,” Phytomedicine, Vol. 16, No. 4, 2009, pp. 287-294. doi:10.1016/j.phymed.2009.02.005
[23]	W. Dimpfel, M. Spuler and H. G. Menge, “Effects of the Antiparkinson Drug Budipine on EEG Activity in Unrestrained Rats,” Arzneimittelforschung, Vol. 39, No. 5, 1989, pp. 560-563.
[24]	W. Dimpfel, M. Spuler and D. E. Nichols, “Hallucinogenic and Stimulatory Amphetamine Derivatives: Fingerprinting DOM, DOI, DOB, MDMA, and MBDB by Spectral Analysis of Brain Field Potentials in the Freely moving Rat (Tele-Stereo-EEG),” Psychopharmacology (Berl), Vol. 98, No. 3, 1989, pp. 297-303. doi:10.1007/BF00451678
[25]	W. Dimpfel, M. Spuler and B. Nickel, “Radioelectroencephalography (Tele-Stereo-EEG) in the Rat as a Pharmacological Model to Differentiate the Central Action of Flupirtine from That of Opiates, Diazepam and Phenobarbital,” Neuropsychobiology, Vol. 16, No. 2-3, 1986, pp. 163-168. doi:10.1159/000118319
[26]	G. Paxinos and C. Watson, “The Rat Brain in Stereotactic Coordinates,” Academic Press, New York, 1982.
[27]	W. Dimpfel, M. Spuler and B. Nickel, “Dose- and Time-Dependent Action of Morphine, Tramadol and Flupirtine as Studied by Radioelectroencephalography in the Freely Behaving Rat,” Neuropsychobiology, Vol. 20, No. 3, 1989, pp. 164-168. doi:10.1159/000118492
[28]	J. L. Price and W. C. Dre-vets, “Neurocircuitry of Mood Disorders,” Neuropsychopharmacology, Vol. 35, No. 1, 2010, pp. 192-216. doi:10.1038/npp.2009.104
[29]	K. J. Ressler and H. S. Mayberg, “Targeting Abnormal Neural Circuits in Mood and Anxiety Disorders: From the Laboratory to the Clinic,” Nature Neuroscience, Vol. 10, No. 9, 2007, pp. 1116-1124. doi:10.1038/nn1944
[30]	L. M. Shin and I. Liberzon, “The Neurocircuitry of Fear, Stress, and Anxiety Disorders” Neuropsychopharmacology, Vol. 35, No. 1, 2010, pp. 169-191. doi:10.1038/npp.2009.83
[31]	R. Cools, “Role of Dopamine in the Motivational and Cognitive Control of Behavior,” Neuroscientist, Vol. 14, No. 4, 2008, pp. 381-395. doi:10.1177/1073858408317009
[32]	M. Pessiglione, B. Seymour, G. Flandin, R. J. Dolan and C. D. Frith, “Dopamine-Dependent Prediction Errors Underpin Reward-Seeking Behaviour in Humans,” Nature, Vol. 442, No. 7106, 2006, pp. 1042-1045. doi:10.1038/nature05051
[33]	B. H. Schott, L. Minuzzi, R. M. Krebs, D. Elmenhorst, M. Lang, O. H. Winz, C. I. Seidenbecher, H. H. Coenen, H. J. Heinze, K. Zilles, E. Duzel and A. Bauer, “Mesolimbic Functional Magnetic Resonance Imaging Activations dur- ing Reward Anticipation Correlate with Reward-Related Ventral Striatal Dopamine Release,” Journal of Neuroscience, Vol. 28, No. 28, 2008, pp. 14311-14319. doi:10.1523/JNEUROSCI.2058-08.2008
[34]	W. Dimp-fel and J. A. Hoffmann, “Electropharmacograms of Rasagiline, Its Metabolite Aminoindan and Selegiline in the Freely Moving Rat,” Neuropsychobiology, Vol. 62, No. 4, 2010, pp. 213-220. doi:10.1159/000319947