GABAergic effects of some foods extracts via inhibition of GABA transaminase (GABA-T)

Year 2021, Volume: 7 Issue: 3, 423 - 428, 31.12.2021

Sümeyye Şahin , Sahra Haas

https://doi.org/10.19127/mbsjohs.976658

Cited By: 1

Abstract

Objective: GABAergic system is a target for various groups of medications including sedatives, anxiolytics, muscle relaxants, antidepressants and antiepileptics. Several foods or food ingredients are able to affect the GABAergic system by the inhibition of the γ-aminobutyric acid (GABA) degrading enzymes including the GABA-transaminase and succinate semialdehyde dehydrogenase. The purpose of this study to investigate the inhibitory effects of tea (Camellia sinensis), coffee (Coffea arabica L.), peppermint (Mentha piperita L.), thyme (Thymus vulgaris L.), and cinnamon (Cinnamomum zeylanicum) on GABA degrading enzymes.
Methods: The inhibition of the GABA-T by aqueous extracts of tea (Camellia sinensis), coffee (Coffea arabica L.), peppermint (Mentha piperita L.), cinnamon (Cinnamomum zeylanicum), and thyme (Thymus vulgaris L.) was investigated using a fluorometric microplate enzyme assay. Dose-dependent inhibition of the GABA-degrading enzymes was attained by all the food extracts tested. For determination of the IC50 values of the extracts (± 95 % CI), a linear regression was performed using Origin® (Origin® 2015G von Origin Lab Corporation, Northampton, MA 01060 USA).
Results: The aqueous extract of black tea presented the strongest inhibitory activity with an IC50-value (half maximal inhibitory concentration) of 13.0 (11.0-15.3) µg/mL. The tested food extracts were successful in inhibiting the GABA-degrading enzymes even at low concentrations.
Conclusion: In conclusion, the selected food extracts could serve as natural inhibitors for GABA-degrading enzymes thus, they could increase the GABA concentration in the brain.   

Keywords

γ-Amino butyric acid, GABA-transaminase, enzyme inhibition, black tea, thyme

References

• 1. Awapara J, Landua AJ, Fuerst R, Seale B. Free γ-aminobutyric acid in brain. J Biol Chem. 1950;187:35-39.
• 2. Baxter CF, Roberts E. The γ-Aminobutyric Acid-α-Ketoglutaric Acid Transaminase of Beef Brain. J Biol Chem. 1958;233(5):1135-1139.
• 3. 3.Roberts E, Frankel S. γ-Aminobutyric acid in brain: Its formation from glutamic acid. J Biol Chem. 1950;187:55-63.
• 4. Wingo WJ, Awapara J. Decarboxylation of L-glutamic acid by brain. J Biol Chem. 1950;187:267-71.
• 5. Bu DF, Erlander MG, Hitz BC, Tillakaratne NJK, Kaufman DL, Wagner-McPherson CB, Evans G A,Tobin AJ. Two human glutamate decarboxylases, 65-kDa GAD and 67-kDa GAD, are each encoded by a single gene. Proc Natl Acad Sci USA. 1992; 89:2115-2119.
• 6. Tsukatani T, Higuchi T, Matsumoto K. Enzyme-based microtiter plate assay for γ-aminobutyric acid: Application to the screening of γ-aminobutyric acid-producing lactic acid bacteria. Analytica Chimica Acta. 2005;540(2):293-297.
• 7. Yogeeswari P, Sriram D, Vaigundaragavendran J. The GABA shunt: an attractive and potential therapeutic target in the treatment of epileptic disorders. Curr Drug Metab. 2005;6(2):127-139. 8. Beleboni RO, Carolino ROG, Pizzo AB, Castellan-Baldan L, Coutinho-Netto J, dos Santos WF, Coimbra NC. Pharmacological and Biochemical Aspects of GABAergic Neurotransmission: Pathological and Neuropsychobiological Relationships. Cellular and Molecular Neurobiology. 2004;24(6):707-728.
• 9. Nitz D, Siegel JM. GABA release in the locus coeruleus as a function of sleep/wake state. Neuroscience. 1977;78(3):795–801.
• 10. Gottesmann C. Brain inhibitory mechanisms involved in basic and higher integrated sleep processes. Brain research Brain research reviews. 2004;45(3):230-249.
• 11. Streeter CC, Whitfield TH, Owen L, Rein T, Karri SK, Yakhkind A, Perlmutter R, Prescot A, Renshaw PF, Ciraulo DA, Jensen JE. Effects of yoga versus walking on mood, anxiety, and brain GABA levels: a randomized controlled MRS study. The Journal of Alternative and Complementary Medicine. 2010;16(11):1145-1152.
• 12. Chang L, Cloak CC, Ernst T. Magnetic resonance spectroscopy studies of GABA in neuropsychiatric disorders. The Journal of Clinical Psychiatry 2003;64 (3):7-14.
• 13. Wood JH, Hare TA, Glaeser BS, Ballenger JC, Post RM. Low cerebrospinal fluid γ-aminobutyric acid content in seizure patients. Neurology. 1979;29(9, Part 1):1203-1208.
• 14. Sanacora G, Mason GF, Rothman DL, Behar KL, Hyder F, Petroff OA, Berman RM, Charney DS, Krystal JH. Reduced cortical γ-aminobutyric acid levels in depressed patients determined by proton magnetic resonance spectroscopy. Arch Gen Psychiatry. 1999 56(11):1043-1047.
• 15. Rimón R, Lepola U, Jolkkonen J, Halonen T, Riekkinen P. Cerebrospinal fluid gamma-aminobutyric acid in patients with panic disorder. Biol Psychiatry 1995;38(11):737-741.
• 16. Knudsen GM, Schmidt J, Almdal T, Paulson OB, Vilstrup H. Passage of Amino Acids and Glucose Across the Blood-brain Barrier in Patients with Hepatic Encephalopathy. Hepatology. 1993;17(6):987-992.
• 17. Meldrum BS. GABAergic mechanisms in the pathogenesis and treatment of epilepsy. Brit J Clin Pharmaco. 1989;27:3S-11S.
• 18. Van Gelder NM, Elliott KAC. Disposition of γ-Aminobutyric Acid Administered to Mammals. Journal of Neurochemisrry. 1958;3:139-143.
• 19. Storici P, De Biase D, Bossa F, Bruno S, Mozzarelli A, Peneff C, Silverman RB, Schirmer T. Structures of g-aminobutyric acid (GABA) aminotransferase, a pyridoxal 5'-phosphate, and [2Fe-2S] cluster-containing enzyme, complexed with g-ethynyl-GABA and with the antiepilepsy drug vigabatrin. J Biol Chem. 2004;279(1):363-373.
• 20. Schechter PJ, Tranier Y, Jung MJ, Böhlen P. Audiogenic seizure protection by elevated brain GABA concentration in mice: effects of γ-acetylenic GABA and γ-vinyl GABA, two irreversible GABA-T inhibitors. European Journal of Pharmacology. 1977;45 319-328.
• 21. Ben-Menachem E. Mechanism of action of vigabatrin: correcting misperceptions. Acta neurologica Scandinavica Supplementum. 2011;124(Suppl. 192):5-15.
• 22. Waterhouse EJ, Mims KN, Gowda SN. Treatment of refractory complex partial seizures: role of vigabatrin. Neuropsych Dis Treat. 2009;5 505–515.
• 23. Beleboni RO, Carolino ROG, Pizzo AB, Castellan-Baldan L, Coutinho-Netto J, Dos Santos WF, Coimbra NC. Pharmacological and Biochemical Aspects of GABAergic Neurotransmission Pathological and Neuropsychobiological Relationships. Cellular and Molecular Neurobiology. 2004;24(6):707-728.
• 24. Awad R, Levac D, Cybulska P, Merali Z, Trudeau VL, Arnason J. T. Effects of traditionally used anxiolytic botanicals on enzymes of the g-aminobutyric acid (GABA) system. Can J Physiol Pharmacol. 2007;85(9):933-942.
• 25. Awad R, Muhammad A, Durst T, Trudeau VL, Arnason JT. Bioassay-guided Fractionation of Lemon Balm (Melissa officinalis L.) using an In Vitro Measure of GABA Transaminase Activity. Phytotherapy Research. 2009;23(8):1075–1081.
• 26. Awad R, Ahmed F, Bourbonnais-Spear N, Mullally M, Ta CA, Tang A, Merali Z, Maquin P, Caal F, Cal V, Poveda L, Vindas PS, Trudeau VL, Arnason JT. Ethnopharmacology of Q’eqchi’ Maya antiepileptic and anxiolytic plants: Effects on the GABAergic system. Journal of Ethnopharmacology. 2009;125(2):257-264.
• 27. Adachi N, Tomonag S, Tachibana T, Denbow DM, Furuse M. (-)-Epigallocatechin gallate attenuates acute stress responses through GABAergic system in the brain. Eur J Pharmacol. 2006;531(1-3):171-175.
• 28. Hossain SJ, Aoshima H, Koda H, Kiso Y. Effects of coffee components on the response of GABAA receptors expressed in Xenopus oocytes. J Agr Food Chem. 2003;51:7568-7575.
• 29. McKay DL, Blumberg JB. A review of the bioactivity and potential health benefits of peppermint tea (Mentha piperita L.). Phytotherapy research: PTR. 2006;20(8):619-933.
• 30. Fachini-Queiroz FC, Kummer R, Estevao-Silva CF, Carvalho MD, Cunha JM, Grespan R, et al. Effects of Thymol and Carvacrol, Constituents of Thymus vulgaris L. Essential Oil, on the Inflammatory Response. Evid Based Complement Alternat Med. 2012;2012:657026.
• 31. Sohrabi R, Pazgoohan N, Seresht HR, Amin B. Repeated systemic administration of the cinnamon essential oil possesses anti-anxiety and anti-depressant activities in mice. Iran J Basic Med Sci. 2017;20(6):708-714.
• 32. Jakoby WB. Enzymes of γ-Aminobutyrate Metabolism (Bacterial). Colowick SP, Kaplan, N.O., editor. New York: Academic Press; 1962. 765-778.
• 33. Lippert BMBW, Jung MJ, Casara P. 4-Amino-hex-5-enoic Acid, a Selective Catalytic Inhibitor of 4-Aminobutyric-Acid Aminotransferase in Mammalian Brain. Eur J Biochem. 1977;74:441-445.
• 34. Awad R, Ahmed F, Bourbonnais-Spear N, Mullally M, Ta CA, Tang A, et al. Ethnopharmacology of Q'eqchi' Maya antiepileptic and anxiolytic plants: effects on the GABAergic system. J Ethnopharmacol. 2009;125(2):257-64.
• 35. Hossain SJ, Hamamoto K, Aoshima H, Hara Y. Effects of tea components on the response of GABAA receptors expressed in Xenopus Oocytes. J Agric Food Chem. 2002;50:3954–3960.
• 36. Vignes M, Maurice T, Lante F, Nedjar M, Thethi K, Guiramand J, Recasens M. Anxiolytic properties of green tea polyphenol (-)-epigallocatechin gallate (EGCG). Brain Res. 2006;1110(1):102-115.
• 37. Higashiyama A, Htay HH, Ozeki M, Juneja LR, Kapoor MP. Effects of L-theanine on attention and reaction time response. Journal of Functional Foods. 2011;3(3):171-178.
• 38. Ali B, Al-Wabel NA, Shams S, Ahamad A, Khan SA, Anwar F. Essential oils used in aromatherapy: A systemic review. Asian Pacific Journal of Tropical Biomedicine. 2015;5(8):601-611.
• 39. Haeseler G, Maue D, Grosskreutz J, Bufler J, Nentwig B, Piepenbrock S, Dengler R, Leuwer M. Voltage-dependent block of neuronal and skeletal muscle sodium channels by thymol and menthol. European Journal of Anaesthesiology 2002;19(8):571–579.
• 40. Galeotti N, Ghelardini C, Mannelli LDC, Mazzanti G, Baghiroli L, Bartolini A. Local Anaesthetic Activity of (+)- and (±)-Menthol. Planta medica. 2001;67 174-6.