ORIGINAL RESEARCH article
Front. Neurosci.
Sec. Neuropharmacology
Volume 19 - 2025 | doi: 10.3389/fnins.2025.1567236
This article is part of the Research TopicTargeting Mitochondrial Dysfunction for the Discovery and Development of Novel CNS Therapies in Rare and Neurodegenerative DiseasesView all 9 articles
Promising neuroprotective potential of naringenin against trimethyltin-induced cognitive deficits and hippocampal neurodegeneration in rats
Provisionally accepted
- 1School of Medicine, Shahed University, Tehran, Iran, Tehran, Iran
- 2Department of Physiology and Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran, Babol, Iran
- 3Neurophysiology Research Center, Shahed University, Tehran, Alborz, Iran
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Learning and memory deficits are clinical characteristics of Alzheimer's disease (AD), often leading to diminished functionality. The neurotoxicant trimethyltin (TMT) is a valuable research tool for inducing cognitive impairment and hippocampal neurodegeneration and studying AD pathogenesis and treatment. Naringenin is a flavonoid with potential neuroprotective effects. This study sought to investigate the neuroprotective potential of naringenin against hippocampal neurodegeneration induced by TMT neurotoxicity and identify some underlying molecular mechanisms. Neurodegeneration was induced through an 8 mg/kg intraperitoneal injection of TMT, followed by oral administration of naringenin (25 and 100 mg/kg) for 21 days. Behavioral assessments, including novel object discrimination (NOD), Y-maze, and passive avoidance tests, were carried out to evaluate cognitive functions. Biochemical assays for oxidative/nitrosative stress, mitochondrial membrane potential (MMP), inflammation, and acetylcholinesterase (AChE) enzyme activity, as well as AD pathology-specific markers, were conducted. To further validate the results, histological assessments of the CA1 hippocampal region using Nissl staining and immunohistochemical identification of 3-nitrotyrosine (3-NT) were performed. Naringenin exhibited a dose-dependent inhibition of CA1 neuronal loss and reversed TMT-induced cognitive deficits. It markedly decreased hippocampal levels of malondialdehyde (MDA), nitrite, tumor necrosis factor-alpha (TNFα), and AChE activity while enhancing catalase and superoxide dismutase (SOD) activities, 3-nitrotyrosine (3-NT) immunoreactivity, and MMP. Furthermore, findings demonstrated that naringenin mitigated the TMT-induced elevation in hippocampal levels of AD-specific proteins, including phosphorylated tau (p-tau), amyloid-beta (Aβ), and presenilin 1. Naringenin may be postulated as a promising therapeutic candidate for AD and related neurodegenerative conditions by mitigating oxidative and nitrosative stress, maintaining mitochondrial integrity, decreasing inflammation, and modulating pathways of neurodegeneration.
Keywords: Alzheimer's disease, Trimethyltin, Naringenin, Neuroprotection, Cognition
Received: 26 Jan 2025; Accepted: 05 May 2025.
Copyright: © 2025 Faryadras, Golchoobian, Iranzadeh and Roghani. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Mehrdad Roghani, Neurophysiology Research Center, Shahed University, Tehran, Alborz, Iran
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.