Proanthocyanidin-Rich-Fraction of Vitis vinifera Seed Abrogates Convulsion Indices: Glutamatergic/ NMDA Inhibition, Enhancement of Anti-Neu N, and NRF2 Expression

doi.org/10.26538/tjnpr/v6i6.23

Authors

  • Opeyemi S. Osuntokun Department of Physiology, Faculty of Basic Medical Sciences, Osun State University Osogbo, Nigeria
  • Samuel O. Oyedokun Department of Physiology, Faculty of Basic Medical Sciences, Osun State University Osogbo, Nigeria
  • Gbola Olayiwola Department of Clinical Pharmacy and Pharmacy Administration, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria
  • Damilare A. Adekomi Department of Anatomy, Faculty of Basic Medical Sciences, Osun State University Osogbo, Nigeria

Keywords:

Convulsion, Proanthocyanidin-rich-fraction, Vitis vinifera seed, Neuroprotection

Abstract

Proanthocyanidins are oligomeric flavonoids with central nervous system activities. This study investigated the mechanisms of  anticonvulsant and neuroprotective effects of proanthocyanidin-rich-fraction (PRF) obtained from Vitis vinifera seed. A total of 90 male Albino mice were challenged with convulsion using picrotoxin, strychnine, or pilocarpine-hydrochloride at 30th minutes of  intraperitoneal injection of 0.9% NaCl (0.2 mL), PRF (200, 100, 50 mg/kg), reference drug, diazepam (7.5 mg/kg), ketamine (0.5 mg/kg), or haloperidol (5 mg/kg) post-treatment. Thereafter, the onset of convulsion and percentage mortality was recorded. The histomorphological and immunohistochemical (glial fibrillary acid protein [GFAP], neuronal nuclear protein [NeuN], and nuclear factor erythroid 2-related factor 2 [NRF2) profiles of the hippocampus were analyzed. Besides marked delay in the onset of convulsion  and percentage mortality in the PRF treatment, especially, there was attenuation in the hippocampal (CA 1) morphological aberrations due to picrotoxin, and pilocarpine-induced convulsion. The GFAP expression was inhibited in the PRF treatment groups. There was an  increase in the intensity score of Anti-Neu N in the PRF treatment groups, while a decrease in expression of the hippocampal neurons was observed across the convulsed mice. The Nrf2 count was decreased due to convulsion but increased significantly in the PRF-treated mice. The delay in seizure onset reduced hippocampal impairment, and mortality due to the convulsion could be traceable to the inhibition of glutamatergic/NMDA transmission and enhancement of Anti-Neu N, and NRF2 expression.

Author Biography

Opeyemi S. Osuntokun, Department of Physiology, Faculty of Basic Medical Sciences, Osun State University Osogbo, Nigeria

Department of Physiology, Faculty of Basic Medical Sciences, Federal University Oye Ekiti, Ekiti State, Nigeria

References

Stafstrom CE and Carmant L. Seizures and epilepsy: an overview for neuroscientists. Cold Spring Harb Perspect Med. 2015; 5(6):a022426.

Beghi E. The Epidemiology of Epilepsy. Neuroepidemiol. 2020; 4(2):185–191.

Sánchez-Fernández I, Goodkin HP, Scott RC. Pathophysiology of convulsive status epilepticus. Seiz. 2019; 68:16-21.

Moreira ELG, Rial D, Duarte FS, de- Carvalho, CR, Horst H, Pizzolatti, MG, Prediger RDS, and Ribeiro-do-Valle RM. Central nervous system activity of the proanthocyanidin-rich fraction obtained from Croton celtidifolius in rats. J Pharm Pharmacol. 2020; 62(8):1061-1068.

Rauf A, Imran M, Abu-Izneid T, Iahtisham-UlHaq, Patel S, Pan X, Naz S, Silva AS, Saeed F, Suleria HAR. Proanthocyanidins: A comprehensive review. Biomed Pharmacother. 2019; 116:108999.

Fernández- Iglesias A, Pajuelo D, Quesada H, Díaz S, Bladé, C, Arola L, Salvadó MJ, Mulero M. Grape seed proanthocyanidin extract improves the hepatic glutathione metabolism in obese Zucker rats. Mol Nutr Food Res. 2014; 58 (4):727-737.

Goldenberg MM. Overview of drugs used for epilepsy and seizures: etiology, diagnosis, and treatment. Pharmacol Ther. 2010; 35(7):392-415.

Ba-Diop A, Marin B, Druet-Cabanac M, Ngoungou EB, Newton CR, Preux PM. Epidemiology, causes, and treatment of epilepsy in sub-Saharan Africa. Lancet Neuro.2014; 13(10):1029-1044.

Prischich F, De Rinaldis M, Bruno F, Egeo G, Santori C, Zappaterreno A, Fattouch J, Di Bonaventura C, Bada J, Russo G, Pizzuti A, Cardona F, Sa'a, Vullo V, Giallonardo A T, D'Erasmo E, Pelliccia A, & Vanacore N. High prevalence of epilepsy in a village in the Littoral Province

of Cameroon. Am J Trop Med Hyg. 2008; 82(2-3):200–210.

Osuntokun OS, Olayiwola G, Adekomi, DA, Oyeyipo IP and Ayoka AO. Proanthocyanidin from Vitis vinifera attenuates memory impairment due to convulsive status epilepticus. Epilep Behav. 2021; 124:108333.

Ishola I, Akindele A, Agbaje E, Ochieng CO, Adeyemi O, Adeyemi O. Anticonvulsant effect of methanolic extract and isolation of active onstituents from Cnestis ferruginea Vahl ex DC (Connaraceae). Annal Pharm Franc. 2014; 42(1):35-41

Gupta G, Dahiya R, Dua K, Chellappan DK, Tiwari J, Narayan Sharma G, Kumar Singh S, Mishra A, Kumar Sharma R, & Agrawal M. Anticonvulsant effect of liraglutide, GLP-1 agonist by averting a change in GABA and brain glutathione level on picrotoxininduced seizures. EXCLI J. 2017; 16:752-754.

Osuntokun OS, Abdulwahab UF, Akanji NO, Adedokun KI, Adekomi DA, Olayiwola G. Anticonvulsant effects of carbamazepine-levetiracetam adjunctive treatment in a convulsive status epilepticus rat model: inhibition of astrogliosis and mortality. Neurosci Lett. 2021;

:136167.

Osuntokun OS, Akingboye BG, Olayiwola G, Abayomi TA, Ayoka AO.The impairment of motor coordination following chronic arbamazepinelevetiracetam combination treatment with evidence of corticocerebellar toxicity in male Wistar rats. Brain Res. 2021; 1767:147565.

Gusel’nikova VV and Korzhevskiy DE. Nen N as a neuronal nuclear antigen and neuron differentiation marker. Acta Naturae. 2015; 7(2):42-47.

Shorvon S and Ferlisi M. The treatment of super-refractory status epilepticus: a critical review of available therapies and a clinical treatment protocol. Brain. 2011; 134:2802–2818.

Sánchez Fernández I, Gaínza-Lein M, Lamb N, Loddenkemper T. Meta-analysis and cost-effectiveness of second-line antiepileptic drugs for status epilepticus. Neurol. 2019; 92(20):e2339–e2348.

Hughes DM, Bonnett LJ, Czanner G, Komarek A, Marson AG and GarciaFinana, M Identification of patients who will not achieve seizure remission within 5 years on AEDs. Neurol. 2018; 91(22):e2035-e2044.

Akula KK, Dhir A, Kulkami SK. Pro-convulsant effects of cefazolinsodium against pentylenetetrazol- or picrotoxin-induced convulsion in ice. Indian J Exp Biol. 2007; 45(8):720-725.

Schuler V, Luscher C, Blanchet C, Klix N, Sansig G, Klebs K, Schmutz M, Heid J, Gentry C. Urban L, Fox A, Spooren W, Jaton AL, Vigouret J, Pozza M, Kelly PH, Mosbacher J, Froestl W, Käslin E, Korn R, Bettler B. Epilepsy, hyperalgesia, impaired memory, and loss of pre- and

postsynaptic GABA(B) responses in mice lacking GABA(B(1). Neuron. 2001; 31(1):47–58.

Wang F, Shing M, Huen Y, Tsang S, Xue Hong. Neuroactive Flavonoids Interacting with GABAA Receptor Complex. Curr Drug Targets CNS

Neurol Disord. 2005; 4(5):575-585.

Figueira I, Garcia G, Pimpão RC, Terrasso AP, Costa I, Almeida AF, Tavares L, Pais TF, Pinto P, Ventura MR, Filipe A, McDougall GJ, Stewart D, Kim KS, Palmela I, Brites D, Brito MA, Brito C, Santos CN. Polyphenols journey through blood-brain barrier towards neuronal protection. Sci Rep. 2017; 7(1):11456.

Hanada T. Ionotropic Glutamate Receptors in Epilepsy: A Review Focusing on AMPA and NMDA Receptors. Biomol. 2020; 10 (464):1-22.

Wang YX, Engelmann T, Xu YF, Schwarz W. Catechins from green tea modulate neurotransmitter transporter activity in Xenopus oocytes. Cogent Biol. 2016; 2:1.

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Published

2022-06-01

How to Cite

S. Osuntokun, O., O. Oyedokun, S., Olayiwola, G., & A. Adekomi, D. (2022). Proanthocyanidin-Rich-Fraction of Vitis vinifera Seed Abrogates Convulsion Indices: Glutamatergic/ NMDA Inhibition, Enhancement of Anti-Neu N, and NRF2 Expression: doi.org/10.26538/tjnpr/v6i6.23. Tropical Journal of Natural Product Research (TJNPR), 6(6), 957–96. Retrieved from https://www.tjnpr.org/index.php/home/article/view/31