Full Article - PDF

Published: 2021-12-27

Page: 947-957


Applied Neuroendocrinology Laboratory, Department of Biology, Faculty of Sciences, Badji Mokhtar Annaba University, Algeria.


Applied Neuroendocrinology Laboratory, Department of Biology, Faculty of Sciences, Badji Mokhtar Annaba University, Algeria.


Applied Neuroendocrinology Laboratory, Department of Biology, Faculty of Sciences, Badji Mokhtar Annaba University, Algeria and Department of Pharmacy, Faculty of Medicine, University of Batna 2, Algeria. 


Applied Neuroendocrinology Laboratory, Department of Biology, Faculty of Sciences, Badji Mokhtar Annaba University, Algeria.

*Author to whom correspondence should be addressed.


Background: The current research explores theimprovementand neuroprotection effects of ginger extract and Nigella sativa oil on working memory and fills the knowledge gap on the neurotoxicity of inorganic mercury in Wistar rats.

Methods: The animals were divided into five equal groups, received by orally to 500 mg/kg/day of ginger extract, 2 ml/kg/day of Nigella Sativa oil for 28 consecutive days (01st – 28th day), and 4 mg/kg/day of mercuric chloride (HgCl2) for 21 consecutive days (08th – 28th day). The rats were exposed each on the 18th day and 28th day respectively in novel object recognition test (NOR) and spontaneous alternation behavior test (Y-maze Test).

Results: The rats were weighed on the 29th day and euthanized,the brains in each group were excisedand weighed.The results obtained show a significant decrease in the relativebrain weight in the rats treated with mercuric chloride alone compared to the control rats. The behavioral tests revealed a decrease in the recognition index and the spontaneous alternation in the group (M) compared to groups (T), (G+M), (N+M), and (G+N+M). The groups pretreated with ginger extract and Nigella Sativa oil reversed these cognitive impairments induced by HgCl2 and improved memorization.

Conclusion: We conclude that ginger extract and Nigella sativa oil exerts a neuroprotective and therapeutic effect against memory disorders induced by mercuric chloride.

Keywords: Mercuric chloride, ginger extract, nigella sativa oil, memory disorders, wistar rats

How to Cite



Download data is not yet available.


Kim MK, Zoh KD. Fate and transport of mercury in environmental media and human exposure. Journal of Preventive Medicine and Public Health. 2012;45(6):335. Available:

World Health Organization. Mercury in health care; 2005.

Schuster PF, Krabbenhoft DP, Naftz DL, Cecil LD, Olson ML, Dewild JF, Abbott ML. Atmospheric mercury deposition during the last 270 years: A glacial ice core record of natural and anthropogenic sources. Environmental Science & Technology. 2002;36(11):2303-2310. Available:

Riley DM, Newby CA, Leal-Almeraz TO, Thomas VM. Assessing elemental mercury vapor exposure from cultural and religious practices. Environmental Health Perspectives. 2001;109(8):779-784. Available:

Goldman LR, Shannon MW. Committee on environmental health. Technical report: Mercury in the environment: implications for pediatricians. Pediatrics. 2001;108(1):197-205. Available:

Obrist D, Kirk JL, Zhang L, Sunderland EM, Jiskra M, Selin NE. A review of global environmental mercury processes in response to human and natural perturbations: Changes of emissions, climate, and land use. Ambio. 2018;47(2):116-140. Available:

Clarkson TW, Magos L. The toxicology of mercury and its chemical compounds. Critical Reviews in Toxicology. 2006;36(8):609-662. Available:

Kang-Yum E, Oransky SH. Chinese patent medicine as a potential source of mercury poisoning. Veterinary and Human Toxicology. 1992;34(3):235-238.

Bernhoft RA. Mercury toxicity and treatment: A review of the literature. Journal of Environmental and Public Health; 2012. Available:

Malqui H, Anarghou H, Ouardi FZ, Ouasmi N, Najimi M, Chigr F. Continuous exposure to inorganic mercury affects neurobehavioral and physiological parameters in mice. Journal of Molecular Neuroscience. 2018;66(2):291-305. Available:

Farouk SM, Gad FA, Almeer R, Abdel-Daim MM, Emam MA. Exploring the possible neuroprotective and antioxidant potency of lycopene against acrylamide-induced neurotoxicity in rats’ brain. Biomedicine & Pharmacotherapy.2021;138:111458. Available:

Hosseini A, Gomar A, Mirazi N, Gomar M. Ameliorating the effect of Zingiber officinale (ginger) hydroethanolic extract on scopolamine-induced memory impairment in adult male rats. Advanced Herbal Medicine. 2016;2(2):35-42.

Aminu I, Teslimat AJ, Victoria W, Samson C, Aboyeji OL, Olatunbosun O, Saliu AM. Nigella sativa oil protected the hippocampus against Acetyl cholinesterase and oxidative dysfunctions-driven impaired working memory in rats. Bulletin of Faculty of Pharmacy, Cairo University. 2019;57(1):25-34. Available:

Ennaceur A, Delacour J. A new one-trial test for neurobiological studies of memory in rats. 1: Behavioral data. Behavioural Brain Research. 1988;31(1):47-59. Available:

Lueptow LM. Novel object recognition test for the investigation of learning and memory in mice. Journal of Visualized Experiments. 2017;126. Available:

Sarti C, Pantoni L, Bartolini L, Inzitari D. Persistent impairment of gait performances and working memory after bilateral common carotid artery occlusion in the adult Wistar rat. Behavioural Brain Research. 2002;136(1):13–20. Available:

Shu Y, Zhang H, Kang T, Zhang J, Yang Y, Liu H, Zhang L. PI3K/Akt Signal Pathway Involved in the Cognitive Impairment Caused by Chronic Cerebral Hypoperfusion in Rats. PLoS ONE. 2013;8(12):e81901. Available:

Bialuk I, Winnicka MM. AM251, cannabinoids receptors ligand, improves recognition memory in rats. Pharmacological Reports. 2011; 63(3):670–679. Available:

Doulames V, Lee S, Shea TB. Environmental enrichment and social interaction improve cognitive function and decrease reactive oxidative species in normal adult mice. International Journal of Neuroscience. 2014; 124(5), 369–376. Available:

Deacon RM, Bannerman DM, Kirby BP, Croucher A, Rawlins JNP. Effects of cytotoxic hippocampal lesions in mice on a cognitive test battery. Behavioural Brain Research. 2002; 133(1):57-68. Available:

Bak J, Pyeon HI, Seok JI, Choi YS. Effect of rotation preference on spontaneous alternation behavior on Y maze and introduction of a new analytical method, entropy of spontaneous alternation. Behavioural Brain Research. 2017; 320:219-224. Available:

Hidaka N, Suemaru K, Li B, Araki H. Effects of repeated electroconvulsive seizures on spontaneous alternation behavior and locomotor activity in rats. Biological and Pharmaceutical Bulletin. 2008;31(10):1928-1932. Available:

National Research Council (NRC). Toxicological Effects of Methylmercury. National Academy Press: Washington DC. 2000;54-56.

Xu F, Farkas S, Kortbeek S, Zhang FX, Chen L, Zamponi GW, Syed NI. Mercury-induced toxicity of rat cortical neurons is mediated through N-methyl-DAspartate receptors. Mol. Brain. 2012;5:30. Available:

Simmons JE, Richardson SD, Speth TF, Miltner RJ, Rice G, Schenck KM, Teuschler LK. Development of a research strategy for integrated technology-based toxicological and chemical evaluation of complex mixtures of drinking water disinfection byproducts. Environmental Health Perspectives. 2002;110(suppl 6), 1013-1024. Available:

Jagadeesan G, Pillai SS. Hepatoprotective effects of taurine against mercury induced toxicity in rat. Journal of Environmental Biology. 2007;28(4):753.

Szumańska G, Gadamski R, Albrecht J. Changes of the Na/K ATPase activity in the cerebral cortical microvessels of rat after single intraperitoneal administration of mercuric chloride: histochemical demonstration with light and electron microscopy. Acta neuropathologica. 1993;86(1):65-70. Available:

Snell RS. Clinical Neuroanatomy. (6thedn). Lippincott Williams & Wilkins Co.: Philadelphia. 2006;298-308.

Aragão WAB, Teixeira FB, Fagundes NCF, Fernandes RM, Fernandes LMP, Da Silva MCF, Lima RR. Hippocampal dysfunction provoked by mercury chloride exposure: evaluation of cognitive impairment, oxidative stress, tissue injury and nature of cell death. Oxidative medicine and cellular longevity; 2018. Available:

Stohs SJ, Bagchi D. Oxidative mechanisms in the toxicity of metalsions. Free Radic. Biol. Med. 1995;18:321-326. Available:

Rao MV, Purohit AR. Neuroprotection by Melatonin on mercury induced toxicity in the rat brain. Pharmacology &Pharmacy. 2011; 2:375-385. Available:

Mello-Carpes PB, Barros W, Borges S, Alves N, Rizzetti D, Pecanha FM, Izquierdo I. Chronic exposure to low mercury chloride concentration induces object recognition and aversive memories deficits in rats. International Journal of Developmental Neuroscience. 2013; 31(7):468-472. Available:

Aschner M, Yao CP, Allen JW, Tan KH. Methylmercury alters glutamate transport in astrocytes. Neurochemistry International.2000;37(2-3)L199-206. Available:

Fanselow MS, Dong HW. Are the dorsal and ventral hippocampus functionally distinct structures? Neuron. 2010;65(1):7-19. Available:

Steckler T, Sahgal A, Aggleton JP, Drinkenburg WHIM. Recognition memory in rats—III. Neurochemical substrates. Progress in neurobiology, 1998;54(3):333-348. Available:

Al Mughairbi F, Nawaz R, Khan F, Hassan A, Mahmood N, Ahmed HT, Bashir A. Neuroprotective effects of Bhilawanol and Anacardic acid during glutamate- induced neurotoxicity. Saudi Pharmaceutical Journal;2021. Available:

Teixeira FB, Leão LKR, Bittencourt LO, Aragão WAB, Nascimento PC, Luz DA, Lima RR. Neurochemical dysfunction in motor cortex and hippocampus impairs the behavioral performance of rats chronically exposed to inorganic mercury. Journal of Trace Elements in Medicine and Biology. 2019;52:143-150. Available:

Chen Z, Ljunggren HG, Bogdanovic N, Nennesmo I, Winblad B, Zhu J. Excitotoxic neurodegeneration induced by intranasal administration of kainic acid in C57BL/6 mice. Brainresearch. 2002;931(2):135-145. Available:

Sanabria ERG, Pereira MFS, Dolnikoff MS, Andrade IS, Ferreira AT, Cavalheiro EA, Fernandes MJS. Deficit in hippocampal long-term potentiation in monosodium glutamate-treated rats. Brain Research Bulletin. 2002; 59(1):47-51. Available:

Wattanathorn J, Jittiwat J, Tongun T, Muchimapura S, Ingkaninan K. Zingiber officinale mitigates brain damage and improves memory impairment in focal cerebral ischemic rat. Evidence-Based Complementary and Alternative Medicine;2011. Available:

Ghayur MN, Gilani AH. Ginger lowers blood pressure through blockade of voltage-dependent calcium channels. Journal of Cardiovascular Pharmacology. 2005;45(1):74-80.

Lim S, Moon M, Oh H, Kim HG, Kim SY, Oh MS. Ginger improves cognitive function via NGF-induced ERK/CREB activation in the hippocampus of the mouse. The Journal of Nutritional Biochemistry. 2014;25(10):1058-1065. Available:

Saenghong N, Wattanathorn J, Muchimapura S, Tongun T, Piyavhatkul N, Banchonglikitkul C, Kajsongkram T. Zingiber officinale improves cognitive function of the middle-aged healthy women. Evidence-Based Complementary and Alternative Medicine; 2012. Available:

Waggas AM. Neuroprotective evaluation of extract of ginger (Zingiber officinale) root in monosodium glutamate-induced toxicity in different brain areas male albino rats. Pakistan Journal of Biological Sciences: PJBS. 2009; 12(3):201-212. Available:

Ghayur MN, Gilani AH, Ahmed T, Khalid A, Nawaz SA, Agbedahunsi JM, Houghton PJ. Muscarinic, Ca++ antagonist and specific butyrylcholinesterase inhibitory activity of dried ginger extract might explain its use in dementia. Journal of Pharmacy and Pharmacology.2008;60(10):1375-1383. Available:

Sahak MKA, Mohamed AM, Hashim NH, Hasan Adli DS. Nigella sativa oil enhances the spatial working memory performance of rats on a radial arm maze. Evidence-Based Complementary and Alternative Medicine; 2013. Available:

Alkis H, Demir E, Taysi MR, Sagir S, Taysi S. Effects of Nigella sativa oil and thymoquinone on radiation-induced oxidative stress in kidney tissue of rats. Biomedicine & Pharmacotherapy. 2021;139:111540. Available:

Azzubaidi MS, Saxena AK, Talib NA, Ahmed QU, Dogarai BB. Protective effect of treatment with black cumin oil on spatial cognitive functions of rats that suffered global cerebrovascular hypoperfusion. Acta Neuro-biologiaeexperimentalis. 2012;72(2):154-165.

Öztürk M. Anticholinesterase and antioxidant activities of Savoury (Saturejathymbra L.) with identified major terpenes of the essential oil. Food Chemistry. 2012;134(1):48-54. Available:

Safithri F, Andriana K. Black Cummin Extract (Nigella sativa Linn) on Spatial Memory Performance in Menopausal Model of Rat. In Proceedings of the Health Science International Conference (HSIC 2017). 2017;254-263.

Nadoushan MJ, Roghani M. The effect of Nigella sativa on learning and memory in male diabetic rats. Iranian Journal of Neuroscience. 2007;1.

Azizi Z, Ebrahimi S, Saadatfar E, Kamalinejad M, Majlessi N. Cognitive-enhancing activity of thymol and carvacrol in two rat models of dementia. Behavioural Pharmacology. 2012;23 (3):241-249. Available:

Jukic M, Politeo O, Maksimovic M, Milos M, Milos M. In vitro acetylcholinesterase inhibitory properties of thymol, carvacrol and their derivatives thymoquinone and thymohydroquinone. Phytotherapy Research. 2007;21(3):259-261. Available:

Fowler A, Goralczyk R, Kilpert C, Mayne-Mechan A, Mohajeri H, Mussler B, Wyss A. U.S. Patent Application No. 2010;12:738-729.

Kanter M. Nigella sativa and derived thymoquinone prevents hippocampal neurodegeneration after chronic toluene exposure in rats. Neurochemical Research. 2008;33(3):579-588. Available:

Malenka RC, Bear MF. LTP and LTD: An embarrassment of riches. Neuron. 2004;44(1):5-21. Available:

Diamond DM, Dunwiddie TV, Rose GM. Characteristics of hippocampal primed burst potentiation in vitro and in the awake rat. Journal of Neuroscience.1988;8(11):4079-4088.


Aburawi SM, Buabeid MA, Auzi A, Mahmud MM, Buabeid MA, Altubuly RA. Enhancing Spatial Memory Effects of Black Seed, Frankincense, and Ginger Extracts Using Albino Mice. Journal of Pharmacy and Pharmacology. 2020;8:245-262. Available: