Therapeutic Effects of Ziziphus mauritiana Leaves Extract on Aluminium Chloride and D-Galactose Induced Cognitive Impairment on the Brain of Wistar Rats: Histological and Biochemical Approach
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1164-1181
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10.58578/ajstea.v3i4.6368
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Authors:
Onesimus Mahdi1*, Aisha Ibrahim Muhammad2, Joshua Rhoda Nuhyite3, Khadijat Abubakar Bobbo4, Gad Gambo5, Lawan Ibrahim Aliyu6, Hosea Joseph7, Galadima Mercy Zubairu8, Yusuf Bhlyakamsu9, Dleve Peter Sodiga10 
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Abstract
Neurodegenerative disorders represent a significant and escalating global healthcare challenge, characterized by the progressive degeneration of neurons and a consequent decline in cognitive and motor functions. Among older adults, Alzheimer’s disease (AD) is the most prevalent neurodegenerative condition, marked by hallmark neuropathological features such as intracellular hyperphosphorylated tau (p-tau) forming neurofibrillary tangles, synaptic dysfunction, neuronal loss, and extracellular amyloid beta (Aβ) plaque accumulation. Aluminium (Al), a known neurotoxic metal, can cross the blood-brain barrier and accumulate in brain tissue, inducing changes associated with neurodegeneration. Additionally, D-galactose (D-gal) is frequently used in animal models to accelerate aging by inducing oxidative stress and inflammation, thus serving as a valuable tool in anti-aging and neurodegenerative research. This study investigates the therapeutic potential of Ziziphus mauritiana extract (ZME), a traditional medicinal plant with recognized nutritional and pharmacological value, in mitigating cognitive dysfunction induced by Aluminium Chloride (AlCl₃) and D-galactose in Wistar rats. Thirty-five healthy adult male rats (80–120 g) were administered D-gal (60 mg/kg, intraperitoneally) and AlCl₃ (200 mg/kg, orally) to induce neurodegeneration. Two experimental groups received ZME at doses of 100 mg/kg and 50 mg/kg, respectively, while the positive control group was treated with donepezil (1 mg/kg). Cognitive function was assessed using the Novel Object Recognition (NOR) test, oxidative stress was evaluated via Superoxide Dismutase (SOD) activity, and histological examination of the prefrontal cortex was conducted to assess neuronal integrity. Results revealed that exposure to AlCl₃ and D-gal significantly impaired cognitive performance, reduced SOD levels (p < 0.05), and induced morphological alterations in the prefrontal cortex. Treatment with ZME significantly improved cognitive performance, elevated SOD activity, and restored cortical architecture, indicating neuroprotective effects. These findings support the potential of Ziziphus mauritiana as a therapeutic agent for mitigating AD-related cognitive impairments through its antioxidative and neuroprotective mechanisms.
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References
Adam P. Swiercz, Mumeko C. Tsuda, Heather A. Cameron (2025). The curious interpretation of novel object recognition tests, Trends in Neurosciences, 48, 4, Pages 250-256, ISSN 0166-2236
Alam, M. A. & Bansal, G. (2020). Effects of Insulin against Aluminium Induced Neurotoxicity in Wistar Rats. Pharmacology and Clinical Pharmacy Research, 5, 62-71.
Ali Ghobadi1,2, Farshad Amini-Behbahani1,2, Azizollah Yousefi3, Maryam Taghavi Shirazi1,2,4, Nasim Behnoud1,2,4* (2019). Medicinal and Nutritional Properties of Ziziphus jujuba Mill. in Traditional Persian Medicine and Modern Phytotherapy. Crescent Journal of Medical and Biological Sciences 6(2),146–150 http://www.cjmb.org eISSN 2148-9696
Aly, H., Elrgal, N., Ali, S., Rizk, M. & Ebrahim, N. (2018). Modulatory effects of Casimiroa edulis on aluminium nanoparticles-associated neurotoxicity in a rat model of induced Alzheimer’s disease. J. Mater. Environ. Sci, 9, 1931-1941.
Anil Kumar1, Jaskirat Sidhu2, Forshing Lui3 and Jack W. Tsao4 (2022). Alzheimer Disease. National Library of Medicine, National Centre for Biotechnology Information
Bitwell, C., Indra, S. S., Luke, C., & Kakoma, M. K. (2023). A review of modern and conventional extraction techniques and their applications for extracting phytochemicals from plants. Scientific African, 19, e01585. https://doi.org/10.1016/j.sciaf.2023.e01585
Biyanzi P. & Doumta C.F. (2024). Antioxidant activities of p-coumaroyl maslinic acid extracted from Fruit of Zizuphus mauritiana Lam.J. Mater. Environ. Sci., 15(7) Page 983-1000
Buniyamin, I., Abd Halim M. F., Eswar, K. A., J Jalani, K., Syed Abd Kadir, S. A. I.A., Mohammad, M., &Khusaimi, Z. (2023). Natural biomolecules in leaves and fruit extracts mediate the biosynthesis of SnO2 nanoparticles: a mini review. International Journal of Pharmaceuticals, Nutraceuticals and Cosmetic Science (IJPNaCS), 6(3), 24-40.
Butt, S. Z., Hussain, S., & Khurram Shahzad. (2021). Phytochemistry of Ziziphus mauritiana: An Overview of its Nutritional and Pharmaceutical Potential.Sci Inquiry Rev.,5(2):01–15. https://doi.org/10.32350/sir/52.01.
Bryliński L, Kostelecka K, Woliński F, Duda P, Góra J, Granat M, Flieger J, Teresiński G, Buszewicz G, Sitarz R, Baj J. (2023). Aluminium in the Human Brain: Routes of Penetration, Toxicity, and Resulting Complications. Int J Mol Sci. 24(8):7228. doi: 10.3390/ijms24087228. PMID: 37108392; PMCID: PMC10139039.
Colomina, M. T. & Peris-Sampedro. (2017). Aluminum and Alzheimer’s Disease. Adv Neurobiol, 18, 183-197.
Denninger, J. K., Smith, B. M., & Kirby, E. D. (2018). Novel object recognition and object location behavioral testing in mice on a budget. Journal of Visualized Experiments, 2018(141), 1–10. https://doi.org/10.3791/58593
Gao, F., Li, S., Xue, G., & Adamu, A. (2024). The role of neuroinflammation in neurodegenerative diseases: Current understanding and future therapeutic targets. Frontiers in Aging Neuroscience, 16, 1347987. https://doi.org/10.3389/fnagi.2024.1347987
Giorgetti, M., Gibbons, J. A., Bernales, S., Alfaro, I. E., La Rochelle, C. D., Cremers, T., Altar, C. A., Wronski, R., Hutter-Paier, B., & Protter, A. A. (2010). Cognition-enhancing properties of dimebon in a rat novel object recognition task are unlikely to be associated with acetylcholinesterase inhibition or N-methyl-D-aspartate receptor antagonism. Journal of Pharmacology and Experimental Therapeutics, 333(3), 748–757. https://doi.org/10.1124/jpet.109.164491
Hwang IK, Yoo KY, Yoo DY, Choi JH, Lee CH, Kang IJ, Kwon DY, Kim YS, Kim DW, Won MH (2011). Zizyphus enhances cell proliferation and neuroblast differentiation in the subgranular zone of the dentate gyrus in middle-aged mice. J Med Food. Mar;14(3):195-200. doi: 10.1089/jmf.2010.1123. PMID: 21332397.
Kandeda, A. K., Nguedia, D., Ayissi, E. R., Kouamouo, J., & Dimo, T. (2021). Ziziphus jujuba (Rhamnaceae) Alleviates Working Memory Impairment and Restores Neurochemical Alterations in the Prefrontal Cortex of D-Galactose-Treated Rats. Evidence-Based Complementary and Alternative Medicine, 2021, 1–15. https://doi.org/10.1155/2021/6610864
Liaquat, L., Saara Ahmad, Sadir, S., Zehra Batool, & Saima Khaliq. (2017). Development of AD like symptoms following coadministration of AlCl3 and D-gal in rats: A neurochemical, biochemical and behavioural study.Pakistan Journal of Pharmaceutical Sciences, 30(2 (Suppl.)), 647-653.
Liu, G., Ma, Y., Li, X., Wang, X., Yang, J., & Yazhong, W. (2024). The protective effect of PL 1-3 on D-galactose-induced aging mice. Frontiers in Pharmacology, 14, 1304801. https://doi.org/10.3389/fphar.2023.1304801
Luo, L., Yan, T., Yang, L., & Zhao, M. (2024). Aluminum chloride and D-galactose induced a zebrafish model of Alzheimer’s disease with cognitive deficits and aging. Computational and Structural Biotechnology Journal, 23, 2230–2239. https://doi.org/10.1016/j.csbj.2024.05.036
Mahdi, O., Chiroma, S. M., Hidayat Baharuldin, M. T., Mohd Nor, N. H., Mat Taib, C. N., Jagadeesan, S., Devi, S., & Mohd Moklas, M. A. (2021). WIN55,212-2 Attenuates Cognitive Impairments in AlCl3 + d-Galactose-Induced Alzheimer’s Disease Rats by Enhancing Neurogenesis and Reversing Oxidative Stress. Biomedicines, 9(9), 1270. https://doi.org/10.3390/biomedicines9091270
Majeed, Z. R., & Abdulrahman, B. R. (2023). A comparative study of scopolamine, D-Galactose and AlCl3-induced Alzheimer’s like disease by enhancing hippocampal neurodegeneration and memory impairment in male rats. Zango Journal of pure and applied Sciences, 35(3). https://doi.org/10.21271/ZJPAS.35.3.19
Mohan Kumar Ramar, Linda Jeeva Kumari Henry, Shiyamsundar Ramachandran, Kumarappan Chidambaram, Ruckmani Kandasamy (2022). Ziziphus mauritiana Lam attenuates inflammation via downregulating NFκB pathway in LPS-stimulated RAW 264.7 macrophages & OVA-induced airway inflammation in mice models, Journal of Ethnopharmacology, 295, 115445, ISSN 0378-8741, https://doi.org/10.1016/j.jep.2022.115445.
Nilofar; Sinan, K.I.; Dall’Acqua, S.; Sut, S.; Uba, A.I.; Etienne, O.K.; Ferrante, C.; Ahmad, J.; Zengin, G. (2024). Ziziphus mauritiana Lam. Bark and Leaves: Extraction, Phytochemical Composition, In Vitro Bioassays and In Silico Studies. Plants 13, 2195. https://doi.org/10.3390/plants13162195
Lueptow, L. M. (2017). Novel Object Recognition Test for the Investigation of Learning and Memory in Mice. Journal of Visualized Experiments, 126, 1–9. https://doi.org/10.3791/55718
Ramli, M. S., Muhammad Adib Wazif Mohd Basir, Universiti Teknologi MARA, Johor Bahru Public Health Laboratory, Muhammad Nurul Azmi, A. F., Universiti Teknologi MARA, Dasiman, R., Universiti Teknologi MARA, Zainon@Zainal, F., Selangor Fruit Valley, Hamid, N., Auckland University of Technology, Siva, R., & Universiti Teknologi MARA. (2025). Phytochemical Screening Of Indian Jujube (Ziziphus mauritiana) And Jackfruit (Artocarpus heterophyllus Lam.) Leaves Extracted By Ultrasound-Assisted Extraction (UAE). Journal of Sustainability Science and Management, 20(1), 139–152. https://doi.org/10.46754/jssm.2025.01.008
Usen, D., & Enogieru, A. B. (2023a). Aluminium chloride-induced prefrontal cortex toxicity in Wistar rats: Evidence from pretreatment with aqueous Psidium guajava leaf extract. Dutse Journal of Pure and Applied Sciences, 9(3b), 1–10. https://doi.org/10.4314/dujopas.v9i3b.1
Wang, X., Yang, J., Li, P., Ma, Y., Li, X., Wang, X., & Liu, G. (2024). The protective effect of PL 1-3 on D-galactose-induced aging mice. Frontiers in Pharmacology, 14, 1304801. https://doi.org/10.3389/fphar.2023.1304801
Xu, Y., Hashimoto, M., Wei, J., Sun, L., & Han, T. (2024). Microglial response to aging and neuroinflammation in the development of neurodegenerative diseases. Neural Regeneration Research, 19(6), 1241–1248. https://doi.org/10.4103/1673-5374.38584