Neuroprotective effects of ethanol extract of Ocimum gratissimum leaf on monosodium glutamate-induced oxidative stress in developing Wistar rat cerebellum


  • Dr. I.O. Imosemi


Background: The safety of monosodium glutamate (MSG) as a flavour enhancer has generated much controversy. This research investigated the neuroprotective effect of ethanolic leaf extract of Ocimum  (OG) against MSG-induced oxidative stress in developing Wistar rat brains. Methods: Thirty pregnant rats were divided randomly into six groups of five animals per group. Control; MSG (4 g/kg); MSG + Vitamin E (500 mg/kg); OG (300 mg/kg dissolved in corn oil) + MSG; OG; Corn oil, CO (vehicle). The pregnant rats received oral administration from day 7 of gestation to postnatal day 28, while the pups received oral administration from the 21st to the 28th postnatal day. Behavioural test was done on day 21 and the pups were killed. The cerebella of pups of days 1, 7, 14, 21 and 28 were dissected out for histological and histomorphometric studies, while biochemical evaluation was done on day 21postpartum.

Results: In the behavioural assessment (open field test), only the rats in the MSG + Vit. E (5.00±1.41) and CO (4.75±1.50) groups showed a significant reduction at p<0.05 compared to the control (19.00±8.71) in longitudinal movement and number of grid lines crossed with four paws within five minutes. Rats in all the treatment groups showed a reduced tendency for rearing compared with the control group at p<0.05. Biochemical analysis showed a decreased glutathione (GSH) and glutathione peroxidase (GSH-Px) activity in the MSG group compared with the control pups, and that OG significantly (P<0.05) increased the GSH and GHS-Px activity compared with MSG animals. Superoxide dismutase (SOD) activity was significantly increased in the control and OG+MSG rats compared with the MSG, OG, MSG + Vit E and cornoil groups at p<0.05. Histological alterations were minimal, with a thicker external granular layer seen in the MSG and MSG+Vit E pups on day 14, and decrwased molecular layer thickness on day 28.

Conclusion: These results suggest that the adverse effects of MSG are mild and OG possesses bioactive phytochemicals capable of preventing and/or reversing MSG-induced oxidative stress. Further studies are recommended to clearly define the mechanism of OG action

Keywords: Ocimum gratissimum, monosodium glutamate, oxidative stress, developing cerebellum, neuroprotection

Contexte: La sécurité du glutamate mono-sodique (MSG) comme stimulateur de saveur a suscité beaucoup de controverse. Cette recherche a étudié l’effet neuro-protecteur de l’extrait éthanoïque de feuilles d’Ocimum gratissimum (OG) contre le stress oxydatif induit par MSG dans le développement des cerveaux de rats Wistar.

Méthodes: Trente rats en gestations ont été divisées de façon aléatoire en six groupes de cinq animaux par groupe. Contrôle; MSG (4 g / kg); MSG + vitamine E (500 mg / kg); OG (300 mg / kg dissous dans de l’huile de maïs) + MSG; OG; Huile de maïs (véhicule). Les rats en gestations ont reçu une administration par voie orale entre le jour 7 de la gestation et le jour 28 postnatal, tandis que les souriceaux ont reçu une administration orale du 21ème au 28ème jour postnatal. Le test de comportement a été effectué le jour 21 et les souriceaux ont été tués. Les cervelets des souriceaux du jour 1, 7, 14, 21 et 28 ont été disséqués pour les études histologiques et histomorphométriques, alors que l’évaluation biochimique a été effectuée le jour 21 après le départ.

Résultats: Dans l’évaluation comportementale (test en champ ouvert), seuls les rats du MSG + Vit. E (5,00 ± 1,41) et les groupes CO (4,75 ± 1,50) ont montré une réduction significative à p <0,05 par rapport au contrôle (19,00 ± 8,71) dans le mouvement longitudinal et le nombre de lignes de grille croisées avec quatre pattes dans les cinq minutes. Les rats dans tous les groupes de traitement ont montré une tendance réduite à l’élevage par rapport au groupe témoin à p <0,05. L’analyse biochimique a montré une activité diminuée de glutathion (GSH) et de glutathion peroxydase (GSH-Px) dans le groupe MSG par rapport  aux chats témoins et que OG a significativement (P <0,05) a augmenté l’activité GSH et GHS-Px par rapport aux animaux MSG. L’activité du super-oxyde dismutase (SOD) a été significativement augmentée dans le contrôle et les rats OG + MSG par rapport aux groupes MSG, OG, MSG + Vit E et control à p <0,05. Les altérations histologiques ont été minimes, avec une couche granulaire externe plus épaisse observée chez les souriceaux MSG et MSG + Vit E le jour 14 et une diminution de l’épaisseur de la couche moléculaire au jour 28.

Conclusion: Ces résultats suggèrent que les effets indésirables du MSG sont doux et le OG possède des phyto-chimiques bioactifs capables de prévenir et / ou inverser le stress oxydatif induit par MSG. D’autres études sont recommandées pour définir clairement le mécanisme de l’action OG

Mots-clés: Ocimum gratissimum, glutamate mono-sodique, stress oxydatif, développement du cervelet, neuro-protection

Correspondence: Dr. I.O. Imosemi, Department of Anatomy, College of Medicine, University of Ibadan, Ibadan, Nigeria. E-mail:


Musa, M. A. and Sunday, A. M. Clumping of the nuclei material of pyramidal Cells of adult Wistar rats following oral administration of monosodium glutamate. Journal of Medical and Health Sciences. 2013; 2 (1): 10-16.

Choi, D.W. Calcium-mediated neurotoxicity: relationship to specific channel types and role in ischemic damage. Trends Neurosci. 1988; 11: 465–467.

Hynd, M. R., Scott, H. L. and Dodd, P. R. Glutamate-mediated excitotoxicity and neurodegeneration in Alzheimer’s disease. Neurochem. Int. 2004; 45: 583-595.

Coyle J.T. and Puttfarcken P. Oxidative stress, glutamate, and neurodegenerative disorders. Science. 1993; 262: 689-695.

Greenwood S.M. and Connolly C.N. Dendritic and mitochondrial changes during glutamate excitotoxicity. Neuropharmacology. 2007; 53: 891-898.

Montal M. Mitochondria glutamate neurotoxicity and the death cascade. Biochem. Biophys. Acta. 1998; 1366: 113-126.

Farombi E. O. and Onyema O. O. Monosodium glutamate-induced oxidative damage and genotoxicity in the rat: modulatory role of vitamin C, vitamin E and Quercetin. Hum Exp Toxicol. 2006; 25: 251–259.

Müller H.M., Kenny E.E. and Sternberg P.W. Textpresso: An Ontology-Based Information Retrieval and Extraction System for Biological Literature. PLoS Biol. 2004; 2(11): e309.

Orwa C., Mutua A., Kindt R., Jamnadass R. and Anthony S. Agroforestree Database: a tree reference and selection guide version 4.0. 2009; 1-4. ( abases.asp).

Afolabi C. Akinmoladun E. O. and Ibukun E., Phytochemical constituent and antioxidant activity of extract from the leaves of Ocimum gratissimum. Scientific Research and Essay. 2007; 2 (5): 163-166.

Meldrum B. S. Implications for neuroprotective treatments. Prog. Brain. Res. 2002; 135: 487-495.

Beyreuther K., Biesalski H. K., Fernstrom. et al. Grimm, P., Hammes, W. P. and Heinemann U. Consensus meeting: monosodium glutamate—an update. Eur J Clin Nutr. 2007; 61: 304–313.

Hermanussen M., Garcia A. P., Sunder M., Voigt M., Salazar V. and Tresguerres J. A. Obesity voracity, and short stature: the impact of glutamate on the regulation of appetite. Eur J Clin Nutr. 2006; 60 (1): 25-31.

Fernandez-Tresguerres and Hernandez J. A. Effect of monosodium glutamate given orally on appetite control (a new theory for the obesity epidemic). An R Acad Nac Med. Madrid. 2005; 122 (2): 341-355.

Von Diemen V. and Trindade M.R.M. Effect of the oral administration of monosodium glutamate during pregnancy and breast-feeding in the offspring of pregnant Wistar rats. Acta Cir Bras. [serial on the Internet]. 2010; 25 (1).

Gabor Horvath D., Vadasz G. Farkas J. and Kiss P. Exposure to Enriched Environment Decreases Neurobehavioral Deficits Induced by Neonatal Glutamate Toxicity. Int. J. Mol. Sci., 2013; 14: 19054-19066

Olopade F. E., Shokunbi M. T. and Siren A. The relationship between ventricular dilatation, neuropathathological and neurobehavioural changes in hydrocephalic rats. Fluids Barriers CNS. 2012; 9: 19.

Miskowiak B. and Partyka M. Neonatal Treatment with Monosodium Glutamate (MSG): Structure of the TSH Immunoreactive Pituitary Cells,” Histology and Histopathology, 2000; 15(2): 415-419.

Rajagopal S.S., Lakshminarayanan G., Rajesh R., et al. Neuroprotective potential of Ocimumsanctum(Linn) leaf extract in monosodium glutamate-induced excitotoxicity. Afr J Pharm Pharmacol. 2013; 7(27): 1894–906.

Reeds P. J. Burrin D. G., Jahoor F., et al. “Enteral Glutamate is almost completely Metabolized in First Pass by the Gastrointestinal Tract of Infant Pigs,” American Journal of Physiology, 1996; 270 (3 Pt. 1): e413-418.

Singhal A., Morris V. B., Labhasetwar V. and Ghorpade, A. Cell death and diseases. Neuroscience. 2013; 4th ed. 903.

Kaur C. and Ling E. Antioxidants and neuroprotection in adult and developing Central Nervous System. Current Medicinal Chemistry. 2013; 15 (29): 3064-3080.

Uttara B., Singh A. V., Zamboni,P. and Mahajan R. T. Oxidative stress and Neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr Neuro Pharma Col. 2009; 7 (1): 65-74.

Dringen R. Metabolism and functions of glutathion in brain. Prog. Neurobiol. 2000; 62: 649-671.

Imosemi I. O. The role of antioxidants in cerebellar development. A review of literature. Int. J. Morphol, 2012; 31 (1): 203-210.






Original Articles