Evaluating the effectiveness of pterostilbene in improving memory and offering neuroprotection in a rat model of Alzheimer’s disease induced by aluminum chloride
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Ameer Raheem Waheed
and
Bahir Abdul Razzaq Mshimesh
Abstract
Background and Objectives
Alzheimer’s disease (AD) is a neurodegenerative disease and is the predominant etiology of dementia. We hypothesize that the naturally occurring pterostilbene (PTE) at doses of 50 and 100 mg/kg would yield dose-dependent neuroprotective effects, reducing cognitive deficits and pathological hallmarks by modulating biomarkers (Amyloid Beta protein (Aβ), Phosphorylated tau protein (P-tau), Brain-Derived Neurotrophic Factor (BDNF), acetylcholinesterase (ACHE), glutamate (GLU)) and a novel synaptic marker neurogranin (NRGN) in rats induced by aluminum chloride (AlCl3). This current research aims to evaluate the neuroprotective effects of pterostilbene (PTE) against neurobehavioral and pathological alterations induced by aluminum chloride (AlCl3) in rats with Alzheimer’s.
Methods
40 rats were divided into five groups, eight in each group. They received 70 mg/kg of body weight AlCl3 intraperitoneally for 30 days, followed by oral administration of PTE at 50 mg/kg or 100 mg/kg, or donepezil at 1 mg/kg for 14 days. The Y-maze and novel object recognition tests were used for the neurobehavioral evaluation of the rats. This was followed by a biochemical evaluation using ELISA kits to demonstrate the impact of PTE on the levels of Aβ, P-tau, BDNF, NRGN, AChE, and GLU. Additional validations were conducted through histopathological evaluation of the cortex and basal ganglia in the rat brain. Using GraphPad Prism 10, statistical data were obtained by ANOVA and Tukey’s multiple comparisons test. The histopathologic score system was determined using the non-parametric Kruskal-Wallis one-way ANOVA k-samples (all pairwise) test.
Results
PTE at 50 mg/kg significantly increases spontaneous alternation percentage (SAP) by 35.7 % and discrimination index (DI) by 79.7 %, while also considerably lowering Aβ by 70.6 %, P-tau by 33.9 %, BDNF by 59.7 %, NRGN by 40 %, ACHE by 28.8 %, and GLU by 28.4 %. Moreover, PTE at 100 mg/kg significantly increases SAP by 42.9 % and DI by 83.4 %, and substantially decreases Aβ by 83.8 %, P-tau by 45.5 %, BDNF by 69 %, NRGN by 42.5 %, ACHE by 69 %, and GLU by 50.9 % compared to the AlCl3 group. Histopathological evaluation of the cortex and basal ganglia in AlCl3-induced rat brains revealed pathological alterations absent in rats treated with PTE.
Conclusions
This study supports the hypothesis that PTE can reverse memory loss and pathological markers.
Acknowledgment
Authors would like to express their gratitude to the College of Pharmacy/ Mustansiriyah University (www.uomustansiriyiah.edu.iq), Baghdad, Iraq, for its support with this work.
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Research ethics: This study was conducted in accordance with the Declaration of Helsinki (as revised in 2013) and approved by the Institutional Review Board Approval no.41 on 10/10/2024.
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Informed consent: Not applicable.
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Author contributions: All authors contributed to the study, accepted responsibility for the entire content of this manuscript, and approved its submission.
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Use of Large Language Models, AI and Machine Learning Tools: Not applicable.
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Conflict of interest: The authors state no conflict of interest.
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Research funding: None declared.
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Data availability: The raw data can be obtained at the request of the corresponding author.
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