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