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Iran J Basic Med Sci. 2017 May;20(5):588-593. doi: 10.22038/IJBMS.2017.8756.

Berberine attenuates convulsing behavior and extracellular glutamate and aspartate changes in 4-aminopyridine treated rats.

Iranian journal of basic medical sciences

Hamid Reza Sadeghnia, Ali Reza Taji, Fatemeh Forouzanfar, Hossein Hosseinzadeh

Affiliations

  1. Neurocognitive Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
  2. Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran.
  3. Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

PMID: 28656093 PMCID: PMC5478786 DOI: 10.22038/IJBMS.2017.8756

Abstract

OBJECTIVES: K+ channel blocker 4-aminopyridine (4-AP) stimulates the release of glutamate from nerve terminals and induces seizures. Berberine as a potential herbal drug exerts several pharmacological actions on the central nervous system including anxiolytic, anticonvulsant, and neuroprotective properties. The present study aimed to investigate the effect of berberine on seizure onset and time course of the extracellular levels of excitatory amino acids (EAA), glutamate and aspartate, changes produced by 4-AP in rat hippocampus.

MATERIALS AND METHODS: The rats were given either saline or berberine (50, 100 and 200 mg/kg, IP) 40 min before administration of 4-AP (15 mg/kg, IP) and the onset of seizure was recorded. A group of rats also received diazepam (DZP, 15 mg/kg, IP) 20 min prior to 4-AP administration. Hippocampal extracellular levels of EAA were also measured using microdialysis assay. Analysis of the dialysate samples was performed by reversed-phase high performance liquid chromatography (HPLC) with precolumn derivatization with o-phthaldialdehyde and fluorescence detection.

RESULTS: Our findings suggest that berberine significantly delayed the seizure onset following 4-AP injection. There was a considerable increase in the extracellular glutamate and aspartate levels in 4-AP treated rats and 4-AP-evoked release of EAA was sharply reduced (about 4-5 fold especially at 20 min after 4-AP administration) in berberine treatment groups.

CONCLUSION: The results of present study show that berberine attenuates 4-AP induced seizures by decreasing hippocampal aspartate and glutamate release in rats.

Keywords: 4-Aminopyridine (4-AP); Barberry; Berberine; Berberis vulgaris; Excitatory amino acids; Seizure

References

  1. Epilepsy Behav. 2010 Jul;18(3):207-10 - PubMed
  2. Fundam Clin Pharmacol. 1991;5(6):503-11 - PubMed
  3. Eur J Pharm Sci. 2012 Aug 15;46(5):415-25 - PubMed
  4. Cancer Lett. 2004 Jan 20;203(2):127-37 - PubMed
  5. Science. 1993 Oct 29;262(5134):689-95 - PubMed
  6. Phytother Res. 2008 Aug;22(8):999-1012 - PubMed
  7. Life Sci. 2005 Oct 28;77(24):3058-67 - PubMed
  8. Neuroreport. 1994 Nov 21;5(17 ):2325-8 - PubMed
  9. Sichuan Da Xue Xue Bao Yi Xue Ban. 2004 Mar;35(2):223-5 - PubMed
  10. Neurosci Lett. 2008 Dec 5;447(1):31-6 - PubMed
  11. Metabolism. 2008 May;57(5):712-7 - PubMed
  12. Neuropsychiatr Dis Treat. 2014 Nov 13;10:2139-45 - PubMed
  13. Chin J Integr Med. 2011 Mar;17 (3):205-11 - PubMed
  14. Iran J Basic Med Sci. 2016 Feb;19(2):125-31 - PubMed
  15. Phytother Res. 2010 Mar;24(3):317-24 - PubMed
  16. Neuropharmacology. 2008 Dec;55(8):1383-90 - PubMed
  17. Iran J Basic Med Sci. 2015 Apr;18(4):334-42 - PubMed
  18. J Pharm Pharm Sci. 2012;15(1):94-102 - PubMed
  19. BMC Neurosci. 2006 Dec 01;7:78 - PubMed
  20. Neuroscience. 2004;125(1):191-201 - PubMed
  21. Epilepsy Res. 2014 Feb;108(2):331-5 - PubMed
  22. Phytomedicine. 2007 Apr;14(4):256-62 - PubMed
  23. J Pharm Pharmacol. 2009 Jul;61(7):831-7 - PubMed
  24. Epilepsy Res. 2003 Jun-Jul;55(1-2):117-29 - PubMed
  25. Sichuan Da Xue Xue Bao Yi Xue Ban. 2003 Jul;34(3):452-4 - PubMed
  26. J Neurosci Res. 2012 Feb;90(2):489-97 - PubMed
  27. Chin J Integr Med. 2010 Apr;16(2):188-92 - PubMed
  28. Biomed Pharmacother. 2017 Mar;87:200-208 - PubMed
  29. Metab Brain Dis. 2013 Sep;28(3):421-8 - PubMed
  30. J Nutr. 2000 Apr;130(4S Suppl):1007S-15S - PubMed
  31. Brain Res. 2008 Jan 2;1187:74-81 - PubMed
  32. Planta Med. 2008 Oct;74(12):1441-5 - PubMed
  33. Brain Res. 2004 Feb 27;999(1):91-7 - PubMed
  34. Pharmacol Rep. 2015 Oct;67(5):970-9 - PubMed
  35. Eur J Pharmacol. 2013 Jan 5;698(1-3):259-66 - PubMed
  36. Biol Pharm Bull. 2009 Jan;32(1):79-85 - PubMed
  37. Mol Cancer Ther. 2006 Feb;5(2):296-308 - PubMed
  38. Neurochem Res. 1997 Dec;22(12):1491-7 - PubMed
  39. PLoS One. 2013 Jun 19;8(6):e67215 - PubMed
  40. Basic Clin Neurosci. 2014 Spring;5(2):124-30 - PubMed
  41. J Neurochem. 1999 May;72(5):2006-14 - PubMed
  42. Eur J Pharmacol. 2007 Aug 13;569(1-2):77-83 - PubMed
  43. Cardiovasc Drug Rev. 2001 Fall;19(3):234-44 - PubMed
  44. J Med Food. 2012 Apr;15(4):413-7 - PubMed

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