Thymoquinone-rich black cumin oil attenuates ibotenic acid-induced excitotoxicity through glutamate receptors in Wistar rats

Inflammation-mediated alterations in glutamate neurotransmission constitute the most important pathway in the pathophysiology of various brain disorders. The excessive signalling of glutamate results in excitotoxicity, neuronal degeneration, and neuronal cell death. In the present study, we investig...

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Main Authors: Sibi P Ittiyavirah, Kannan Ramalingam, Arathy Sathyan, R.S. Rajasree, Mohamed Saheer Kuruniyan, Syed Altafuddin Quadri, Muhammed Elayadeth-Meethal, Punnoth Poonkuzhi Naseef
Format: Article
Language:English
Published: Elsevier 2022-12-01
Series:Saudi Pharmaceutical Journal
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1319016422002559
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author Sibi P Ittiyavirah
Kannan Ramalingam
Arathy Sathyan
R.S. Rajasree
Mohamed Saheer Kuruniyan
Syed Altafuddin Quadri
Muhammed Elayadeth-Meethal
Punnoth Poonkuzhi Naseef
author_facet Sibi P Ittiyavirah
Kannan Ramalingam
Arathy Sathyan
R.S. Rajasree
Mohamed Saheer Kuruniyan
Syed Altafuddin Quadri
Muhammed Elayadeth-Meethal
Punnoth Poonkuzhi Naseef
author_sort Sibi P Ittiyavirah
collection DOAJ
description Inflammation-mediated alterations in glutamate neurotransmission constitute the most important pathway in the pathophysiology of various brain disorders. The excessive signalling of glutamate results in excitotoxicity, neuronal degeneration, and neuronal cell death. In the present study, we investigated the relative efficacy of black cumin (Nigella sativa) oil with high (5 % w/w) and low (2 % w/w) thymoquinone content (BCO-5 and BCO-2, respectively) in alleviating ibotenic acid-induced excitotoxicity and neuroinflammation in Wistar rats. It was found that BCO-5 reversed the abnormal behavioural patterns and the key inflammatory mediators (TNF-α and NF-κB) when treated at 5 mg/kg body weight. Immunohistochemical studies showed the potential of BCO-5 to attenuate the glutamate receptor subunits NMDA and GluR-2 along with increased glutamate decarboxylase levels in the brain tissues. Histopathological studies revealed the neuroprotection of BCO-5 against the inflammatory lesions, as evidenced by the normal cerebellum, astrocytes, and glial cells. BCO-2 on the other hand showed either a poor protective effect or no effect even at a 4-fold higher concentration of 20 mg/kg body weight indicating a very significant role of thymoquinone content on the neuroprotective effect of black cumin oil and its plausible clinical efficacy in counteracting the anxiety and stress-related neurological disorders under conditions such as depression and Alzheimer's disease.
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spelling doaj.art-6017143cd40449f0806c693e9942061e2022-12-23T04:40:01ZengElsevierSaudi Pharmaceutical Journal1319-01642022-12-01301217811790Thymoquinone-rich black cumin oil attenuates ibotenic acid-induced excitotoxicity through glutamate receptors in Wistar ratsSibi P Ittiyavirah0Kannan Ramalingam1Arathy Sathyan2R.S. Rajasree3Mohamed Saheer Kuruniyan4Syed Altafuddin Quadri5Muhammed Elayadeth-Meethal6Punnoth Poonkuzhi Naseef7Department of Pharmaceutical Sciences, Centre for Professional and Advanced Sciences, Cheruvandoor, Kottayam 686631, IndiaDepartment of Pharmaceutical Sciences, Centre for Professional and Advanced Sciences, Cheruvandoor, Kottayam 686631, IndiaDepartment of Pharmaceutical Sciences, Centre for Professional and Advanced Sciences, Cheruvandoor, Kottayam 686631, IndiaCollege of Pharmaceutical Sciences, Government Thirumala Devaswom Medical College, Alappuzha 688005, IndiaDepartment of Dental Technology, College of Applied Medical Sciences, King Khalid University, Abha 61421, Saudi ArabiaDepartment of Dental Technology, College of Applied Medical Sciences, King Khalid University, Abha 61421, Saudi ArabiaDepartment of Animal Breeding and Genetics, College of Veterinary and Animal Sciences, Kerala Veterinary and Animal Sciences University, Pookode, Wayanad 675621, IndiaDepartment of Pharmaceutics, Moulana College of Pharmacy, Perinthalmanna 679321, India; Corresponding author.Inflammation-mediated alterations in glutamate neurotransmission constitute the most important pathway in the pathophysiology of various brain disorders. The excessive signalling of glutamate results in excitotoxicity, neuronal degeneration, and neuronal cell death. In the present study, we investigated the relative efficacy of black cumin (Nigella sativa) oil with high (5 % w/w) and low (2 % w/w) thymoquinone content (BCO-5 and BCO-2, respectively) in alleviating ibotenic acid-induced excitotoxicity and neuroinflammation in Wistar rats. It was found that BCO-5 reversed the abnormal behavioural patterns and the key inflammatory mediators (TNF-α and NF-κB) when treated at 5 mg/kg body weight. Immunohistochemical studies showed the potential of BCO-5 to attenuate the glutamate receptor subunits NMDA and GluR-2 along with increased glutamate decarboxylase levels in the brain tissues. Histopathological studies revealed the neuroprotection of BCO-5 against the inflammatory lesions, as evidenced by the normal cerebellum, astrocytes, and glial cells. BCO-2 on the other hand showed either a poor protective effect or no effect even at a 4-fold higher concentration of 20 mg/kg body weight indicating a very significant role of thymoquinone content on the neuroprotective effect of black cumin oil and its plausible clinical efficacy in counteracting the anxiety and stress-related neurological disorders under conditions such as depression and Alzheimer's disease.http://www.sciencedirect.com/science/article/pii/S1319016422002559Black cuminExcitotoxicityIbotenic acidNeuroinflammationNigella sativaThymoquinone
spellingShingle Sibi P Ittiyavirah
Kannan Ramalingam
Arathy Sathyan
R.S. Rajasree
Mohamed Saheer Kuruniyan
Syed Altafuddin Quadri
Muhammed Elayadeth-Meethal
Punnoth Poonkuzhi Naseef
Thymoquinone-rich black cumin oil attenuates ibotenic acid-induced excitotoxicity through glutamate receptors in Wistar rats
Saudi Pharmaceutical Journal
Black cumin
Excitotoxicity
Ibotenic acid
Neuroinflammation
Nigella sativa
Thymoquinone
title Thymoquinone-rich black cumin oil attenuates ibotenic acid-induced excitotoxicity through glutamate receptors in Wistar rats
title_full Thymoquinone-rich black cumin oil attenuates ibotenic acid-induced excitotoxicity through glutamate receptors in Wistar rats
title_fullStr Thymoquinone-rich black cumin oil attenuates ibotenic acid-induced excitotoxicity through glutamate receptors in Wistar rats
title_full_unstemmed Thymoquinone-rich black cumin oil attenuates ibotenic acid-induced excitotoxicity through glutamate receptors in Wistar rats
title_short Thymoquinone-rich black cumin oil attenuates ibotenic acid-induced excitotoxicity through glutamate receptors in Wistar rats
title_sort thymoquinone rich black cumin oil attenuates ibotenic acid induced excitotoxicity through glutamate receptors in wistar rats
topic Black cumin
Excitotoxicity
Ibotenic acid
Neuroinflammation
Nigella sativa
Thymoquinone
url http://www.sciencedirect.com/science/article/pii/S1319016422002559
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