Nigella Sativa Oil Protects Against Aluminium Chloride-Induced Cognitive Impairment Via Modulation of Cholinergic Activity, Brain Neurotransmitter, and Oxidative Stress

Ayodeji Oluwatobi Ojetunde, Abdulwahab Alhassan, Ibrahim Suleiman, Ahmed Sherif Isa

Abstract


Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and memory impairment, with no known cure. This study investigated the potential protective effects of Nigella sativa oil (NSO) on aluminium chloride-induced cognitive impairment in Wistar rats. Twenty-four rats were divided into four groups. Group I received 1 ml/kg of distilled water. Groups II-IV were administered aluminium chloride (100 mg/kg). Groups III and IV were co-treated with NSO at 1 ml/kg and 2 ml/kg, respectively. Neurobehavioral assessments (Morris water maze and Y-maze) were performed, followed by biochemical analysis of brain tissues. Aluminium chloride significantly (p < 0.05) impaired spatial learning and memory and decreased the percentage of alternation. It also significantly (p < 0.05) increased acetylcholinesterase level, glutamate concentration, and malondialdehyde level, and decreased antioxidant markers. Meanwhile, Nigella sativa oil (1 ml/kg and 2 ml/kg) significantly (p < 0.05) improved learning ability and spatial memory, and increased percentage alternation in the Y-maze test. Nigella sativa oil also significantly (p < 0.05) decreases acetylcholinesterase, glutamate, and malondialdehyde, and increases antioxidant biomarkers. This study showed that Nigella sativa oil can improve cognitive and spatial learning functions via modulation of cholinergic activity, brain neurotransmitters, and oxidative stress.


Keywords


Aluminium chloride; Alzheimer’s disease; Cognitive impairment; Nigella sativa oil; Oxidative stress

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Abbas, F., Eladl, M. A., El-Sherbiny, M., Abozied, N., Nabil, A., Mahmoud, S. M., ... & Ibrahim, D. (2022). Celastrol and thymoquinone alleviate aluminum chloride-induced neurotoxicity: Behavioral psychomotor performance, neurotransmitter level, oxidative-inflammatory markers, and BDNF expression in rat brain. Biomedicine & Pharmacotherapy, 151, 113072. https://doi.org/10.1016/j.biopha.2022.113072

Abulfadl, Y. S., El-Maraghy, N. N., Ahmed, A. A. E., Nofal, S., & Badary, O. A. (2018). Protective effects of thymoquinone on D-galactose and aluminum chloride induced neurotoxicity in rats: biochemical, histological and behavioral changes. Neurological Research, 40(4), 324–333. https://doi.org/10.1080/01616412.2018.1441776

Alghamdi, B. S. A. (2018). Possible prophylactic anti-excitotoxic and anti-oxidant effects of virgin coconut oil on aluminium chloride-induced Alzheimer's in rat models. Journal of Integrative Neuroscience, 17(3-4), 593–607. https://doi.org/10.3233/JIN-180089

Anwar, H. M., Georgy, G. S., Hamad, S. R., Badr, W. K., El Raey, M. A., Abdelfattah, M. A. O., Wink, M., & Sobeh, M. (2021). A leaf extract of Harrisonia abyssinica ameliorates neurobehavioral, histological and biochemical changes in the hippocampus of rats with aluminum chloride-induced Alzheimer's Disease. Antioxidants, 10(6), 947. https://doi.org/10.3390/antiox10060947

Asadbegi, M., Yaghmaei, P., Salehi, I., Komaki, A., & Ebrahim-Habibi, A. (2017). Investigation of thymol effect on learning and memory impairment induced by intrahippocampal injection of amyloid beta peptide in high fat diet- fed rats. Metabolic Brain Disease, 32(3), 827-839. https://doi.org/10.1007/s11011-017-9960-0

Auti, S. T., & Kulkarni, Y. A. (2019). Neuroprotective effect of cardamom oil against aluminum induced neurotoxicity in rats. Frontiers in Neurology, 10, 399. https://doi.org/10.3389/fneur.2019.00399

Baburaj, R., Sandur V, R., & Das, K. (2023). Neuroprotective role of a protoberberine alkaloid against aluminum-induced neuroinflammation and excitotoxicity. Notulae Scientia Biologicae, 15(2), 11488-11488. https://doi.org/10.55779/nsb15211488

Bargi, R., Asgharzadeh, F., Beheshti, F., Hosseini, M., Sadeghnia, H. R., & Khazaei, M. (2017). The effects of thymoquinone on hippocampal cytokine level, brain oxidative stress status and memory deficits induced by lipopolysaccharide in rats. Cytokine, 96, 173-184. https://doi.org/10.1016/j.cyto.2017.04.015

Beigom Hejaziyan, L., Hosseini, S. M., Taravati, A., Asadi, M., Bakhshi, M., Moshaei Nezhad, P., ... & Mououdi, M. (2023). Effect of Rosa damascena extract on rat model Alzheimer’s disease: a histopathological, behavioral, enzyme activities, and oxidative stress study. Evidence?Based Complementary and Alternative Medicine, 2023(1), 4926151. https://doi.org/10.1155/2023/4926151

Boland, B., Yu, W. H., Corti, O., Mollereau, B., Henriques, A., Bezard, E., ... & Millan, M. J. (2018). Promoting the clearance of neurotoxic proteins in neurodegenerative disorders of ageing. Nature Reviews Drug Discovery, 17(9), 660-688. https://doi.org/10.1038/nrd.2018.109

Colizzi, C. (2018). The protective effects of polyphenols on Alzheimer's disease: A systematic review. Alzheimer's & Dementia: Translational Research & Clinical Interventions, 5, 184-196. https://doi.org/10.1016/j.trci.2018.09.002

Ekundayo, B. E., Obafemi, T. O., Afolabi, B. A., Adewale, O. B., Onasanya, A., Osukoya, O. A., ... & Adu, I. A. (2022). Gallic acid and hesperidin elevate neurotransmitters level and protect against oxidative stress, inflammation and apoptosis in aluminum chloride-induced Alzheimer's disease in rats. Pharmacological Research-Modern Chinese Medicine, 5, 100193. https://doi.org/10.1016/j.prmcm.2022.100193

Ellman, G. L. (1959). Tissue sulfhydryl groups. Archives of Biochemistry and Biophysics, 82(1), 70–77. https://doi.org/10.1016/0003-9861(59)90090-6

Elmaci, I., & Altinoz, M. A. (2016). Thymoquinone: An edible redox-active quinone for the pharmacotherapy of neurodegenerative conditions and glial brain tumors. A short review. Biomedicine & Pharmacotherapy, 83, 635–640. https://doi.org/10.1016/j.biopha.2016.07.018

El-Naggar, T., Gómez-Serranillos, M. P., Palomino, O. M., Arce, C., & Carretero, M. E. (2010). Nigella sativa L. seed extract modulates the neurotransmitter amino acids release in cultured neurons in vitro. BioMed Research International, 2010(1), 398312. https://doi.org/10.1155/2010/398312

Elreedy, H. A., Elfiky, A. M., Mahmoud, A. A., Ibrahim, K. S., & Ghazy, M. A. (2023). Neuroprotective effect of quercetin through targeting key genes involved in aluminum chloride induced Alzheimer’s disease in rats. Egyptian Journal of Basic and Applied Sciences, 10(1), 174-184. https://doi.org/10.1080/2314808X.2022.2164136

Esterbauer, H., & Cheeseman, K. H. (1990). Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. In Methods in enzymology (Vol. 186, pp. 407-421). Academic Press. https://doi.org/10.1016/0076-6879(90)86134-H

Field, R. H., Gossen, A., & Cunningham, C. (2012). Prior pathology in the basal forebrain cholinergic system predisposes to inflammation-induced working memory deficits: Reconciling inflammatory and cholinergic hypotheses of delirium. The Journal of Neuroscience, 32(18), 6288. https://doi.org/10.1523/JNEUROSCI.4673-11.2012

Folarin, R. O., Surajudeen, O. B., Omotosho, E. O., Owoniyi, A. O., Oyeleye, D. O., & Shallie, P. (2020). Motor co-ordinative roles of Nigella sativa oil in mice models of phenol-induced essential tremor. Annals of Health Research, 6(1), 85-99. https://doi.org/10.30442/ahr.0601-10-70

Fridovich, I. (1989). Superoxide dismutases: an adaptation to a paramagnetic gas. Journal of Biological Chemistry, 264(14), 7761-7764. https://doi.org/10.1016/S0021-9258(18)83102-7

Gasparini, L., & Dityatev, A. (2008). Beta-amyloid and glutamate receptors. Experimental Neurology, 212(1), 1-4. https://doi.org/10.1016/j.expneurol.2008.03.005

Habila, N., Inuwa, H. M., Aimola, I. A., Lasisi, O. I., Chechet, D. G., & Okafor, I. A. (2012). Correlation of acetylcholinesterase activity in the brain and blood of wistar rats acutely infected with Trypanosoma congolense. Journal of Acute Disease, 1(1), 26-30. https://doi.org/10.1016/S2221-6189(13)60006-2

Hamdan, A. M. E., Alharthi, F. H. J., Alanazi, A. H., El-Emam, S. Z., Zaghlool, S. S., Metwally, K., ... & Abu-Elfotuh, K. (2022). Neuroprotective effects of phytochemicals against aluminum chloride-induced Alzheimer’s disease through ApoE4/LRP1, wnt3/?-catenin/gsk3?, and TLR4/NLRP3 pathways with physical and mental activities in a rat model. Pharmaceuticals, 15(8), 1008. https://doi.org/10.3390/ph15081008

Hosseinzadeh, H., Taiari, S., & Nassiri-Asl, M. (2012). Effect of thymoquinone, a constituent of Nigella sativa L., on ischemia-reperfusion in rat skeletal muscle. Naunyn-Schmiedeberg's archives of pharmacology, 385(5), 503-508. https://doi.org/10.1007/s00210-012-0726-2

Imam, A., Ajao, M. S., Ajibola, M. I., Amin, A., Abdulmajeed, W. I., Lawal, A. Z., ... & Adana, M. Y. (2016). Black seed oil ameliorated scopolamine-induced memory dysfunction and cortico-hippocampal neural alterations in male Wistar rats. Bulletin of faculty of pharmacy, cairo university, 54(1), 49-57. https://doi.org/10.1016/j.bfopcu.2015.12.005

Imam, A., Oyegbola, C., Busari, M., Jaji-Sulaimon, R., Alli-Oluwafuyi, A., & Okesina, A. A. (2021). Nigella sativa oil preserved anxiety-like, motor and memory related behaviours and neuronal integrity in dichlorvos induced acetyl cholinesterase inhibitions in rats. Nigerian Journal of Neuroscience, 12(3), 84-91. http://dx.doi.org/10.47081/njn2021.12.3/002

Jukic, M., Politeo, O., Maksimovic, M., Milos, M., & Milos, M. (2007). In Vitro acetylcholinesterase inhibitory properties of thymol, carvacrol and their derivatives thymoquinone and thymohydroquinone. Phytotherapy Research, 21(3), 259-261. https://doi.org/10.1002/ptr.2063

Khan, R. A., Najmi, A. K., Khuroo, A. H., Goswami, D., & Akhtar, M. (2014). Ameliorating effects of thymoquinone in rodent models of schizophrenia. African Journal of Pharmacy and Pharmacology, 8(15), 413-421.

Kim, K., Lee, S. G., Kegelman, T. P., Su, Z. Z., Das, S. K., Dash, R., ... & Fisher, P. B. (2011). Role of excitatory amino acid transporter?2 (EAAT2) and glutamate in neurodegeneration: opportunities for developing novel therapeutics. Journal of Cellular Physiology, 226(10), 2484-2493. https://doi.org/10.1002/jcp.22609

Kooti, W., Hasanzadeh-Noohi, Z., Sharafi-Ahvazi, N., Asadi-Samani, M., & Ashtary-Larky, D. (2016). Phytochemistry, pharmacology, and therapeutic uses of black seed (Nigella sativa). Chinese Journal of Natural Medicines, 14(10), 732-745. https://doi.org/10.1016/S1875-5364(16)30088-7

Lao, K., Ji, N., Zhang, X., Qiao, W., Tang, Z., & Gou, X. (2019). Drug development for Alzheimer's disease: review. Journal of Drug Targeting, 27(2), 164-173. https://doi.org/10.1080/1061186X.2018.1474361

Lotfi, M., Kazemi, S., Ebrahimpour, A., Pourabdolhossein, F., Satarian, L., Eghbali, A., & Moghadamnia, A. A. (2022). Thymoquinone improved nonylphenol-induced memory deficit and neurotoxicity through its antioxidant and neuroprotective effects. Molecular Neurobiology, 59(6), 3600-3616. https://doi.org/10.1007/s12035-022-02807-5

Mahboubi, M., Taghizadeh, M., Talaei, S. A., Firozeh, S. M. T., Rashidi, A. A., & Tamtaji, O. R. (2016). Combined administration of Melissa officinalis and Boswellia serrata extracts in an animal model of memory. Iranian Journal of Psychiatry and Behavioral Sciences, 10(3), e681. https://doi.org/10.17795/ijpbs-681

Mohamed, A. B., Mohamed, A. Z., & Aly, S. (2020). Effect of Thymoquinone against Aluminum Chloride-Induced Alzheimer-Like Model in Rats: A Neurophysiological and Behavioral Study. The Medical Journal of Cairo University, 88(1), 355-365. https://dx.doi.org/10.21608/mjcu.2020.93997

Niu Q. (2018). Overview of the relationship between aluminum exposure and health of human being. Advances in Experimental Medicine and Biology, 1091, 1–31. https://doi.org/10.1007/978-981-13-1370-7_1

Norouzi, F., Hosseini, M., Abareshi, A., Beheshti, F., Khazaei, M., Shafei, M. N., Soukhtanloo, M., Gholamnezhad, Z., & Anaeigoudari, A. (2019). Memory enhancing effect of Nigella Sativa hydro-alcoholic extract on lipopolysaccharide-induced memory impairment in rats. Drug and Chemical Toxicology, 42(3), 270-279. https://doi.org/10.1080/01480545.2018.1447578

Ojetunde, A. O. (2021). Antidiabetic effects of medicinal plants. Eastern Ukrainian Medical Journal, 9(1), 1-17. https://doi.org/10.21272/eumj.2021;9(1):1-17

Ojetunde, A. O. (2024). The neuroprotective and therapeutic effects of medicinal plants and natural products against aluminium chloride-induced Alzheimer’s Disease: Recent Update. Biology, Medicine, & Natural Product Chemistry, 13(1), 7-33. https://doi.org/10.14421/biomedich.2024.131.7-33

Ojetunde, A. O., Tongshuwar, G. T., Oyegoke, A. F., & Oyegoke, T. (2021). An ethno-botanical survey of plants used in rheumatoid arthritis treatment: A case study of Gusau in Nigeria. Herbal Medicines Journal, 6(4), 135-145. https://doi.org/10.22087/hmj.v6i4.868

Ramos-Rodriguez, J. J., Pacheco-Herrero, M., Thyssen, D., Murillo-Carretero, M. I., Berrocoso, E., Spires-Jones, T. L., ... & Garcia-Alloza, M. (2013). Rapid ?-amyloid deposition and cognitive impairment after cholinergic denervation in APP/PS1 mice. Journal of Neuropathology & Experimental Neurology, 72(4), 272-285. https://doi.org/10.1097/NEN.0b013e318288a8dd

Rout, S. K., Kar, D. M., & Rout, A. B. (2012). Study of central nervous system activity of leaf extracts of nerium oleanderin experimental animal models. International Journal of Pharmacy and Pharmaceutical Sciences, 4(4), 378-382.

Safhi, M. M. (2016). Neuromodulatory effects of thymoquinone in extenuating oxidative stress in chlorpromazine treated rats. Acta Poloniae Pharmaceutica, 73(2), 529-535.

Sahak, M. K. A., Kabir, N., Abbas, G., Draman, S., Hashim, N. H., & Hasan Adli, D. S. (2016). The role of Nigella sativa and its active constituents in learning and memory. Evidence?Based Complementary and Alternative Medicine, 2016(1), 6075679. https://doi.org/10.1155/2016/6075679

Singh, B., Day, C. M., Abdella, S., & Garg, S. (2024). Alzheimer's disease current therapies, novel drug delivery systems and future directions for better disease management. Journal of Controlled Release, 367, 402-424. https://doi.org/10.1016/j.jconrel.2024.01.047

Sinha, A. K. (1972). Colorimetric assay of catalase. Analytical Biochemistry, 47(2), 389-394. https://doi.org/10.1016/0003-2697(72)90132-7

Sudha, S., Janani, C., Chitra, B., & Nisha, S. A. (2021). Assessment of histoarchitecture antioxidant and anti-cholinesterase activity of methanolic extract from nigella sativa linn. Gorteria, 34(6), 263-280.

Tongshuwar, G. T., Ojetunde, A. O., Oyegoke, A. F., & Oyegoke,T. (2020). Ethno-botanical survey of plants used in a rheumatoid arthritis treatment: A case study of Jos in Nigeria. Medical Science of Ukraine (MSU), 16(4), 35-45. https://doi.org/10.32345/2664-4738.4.2020.6

Umar, S., Zargan, J., Umar, K., Ahmad, S., Katiyar, C. K., & Khan, H. A. (2012). Modulation of the oxidative stress and inflammatory cytokine response by thymoquinone in the collagen induced arthritis in Wistar rats. Chemico-Biological Interactions, 197(1), 40-46. https://doi.org/10.1016/j.cbi.2012.03.003

Vaz, M., Silva, V., Monteiro, C., & Silvestre, S. (2022). Role of Aducanumab in the treatment of Alzheimer's Disease: Challenges and opportunities. Clinical Interventions in Aging, 17, 797-810. https://doi.org/10.2147/CIA.S325026

Weil, Z. M., Norman, G. J., DeVries, A. C., & Nelson, R. J. (2008). The injured nervous system: A Darwinian perspective. Progress in Neurobiology, 86(1), 48-59. https://doi.org/10.1016/j.pneurobio.2008.06.001

Zaher, M. F., Bendary, M. A., Abd El-Aziz, G. S., & Ali, A. S. (2019). Potential protective role of thymoquinone on experimentally-induced Alzheimer rats. Journal of Pharmaceutical Research International, 31(6), 1-18.

Zatta, P., Ibn-Lkhayat-Idrissi, M., Zambenedetti, P., Kilyen, M., & Kiss, T. (2002). In vivo and in vitro effects of aluminum on the activity of mouse brain acetylcholinesterase. Brain Research Bulletin, 59(1), 41-45. https://doi.org/10.1016/S0361-9230(02)00836-5




DOI: https://doi.org/10.14421/biomedich.2025.142.739-746

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Copyright (c) 2025 Ayodeji Oluwatobi Ojetunde, Abdulwahab Alhassan, Ibrahim Suleiman, Ahmed Sherif Isa



Biology, Medicine, & Natural Product Chemistry
ISSN 2089-6514 (paper) - ISSN 2540-9328 (online)
Published by Sunan Kalijaga State Islamic University & Society for Indonesian Biodiversity.

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