Blueberry anthocyanins ameliorate arsenic-induced cognitive impairment in rats: mitigating mitochondrial damage and dysregulation

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-07-08 DOI:10.1016/j.phymed.2025.157062

Xinbo Ma , Yang Liu , Bo Ding , Yanan Liu , Yuchen Zhang , Yuxi Wang , Liu Yang , Yanmei Yang , Xiaona Liu

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Abstract

Background

Blueberry anthocyanin extract (BAE) is a natural antioxidant flavonoid found in blueberries that has the potential to alleviate oxidative stress-induced neurodegeneration. Previous studies have demonstrated the potential of BAE to mitigate arsenic-induced cognitive impairment; however, the underlying protective mechanisms remain elusive.

Purpose

This study aimed to evaluate the effectiveness of BAE in reducing arsenic-induced cognitive impairment and explored whether BAE's neuroprotective effects are related to its antioxidant and mitochondrial protective effects.

Methods

Sixty male rats were exposed to sodium arsenite (NaAsO₂, 10 mg/kg) with or without BAE (100 and 200 mg/kg) for 12 weeks. Spatial learning and memory were evaluated using the Morris water maze (MWM). Neuronal damage in rat hippocampi was evaluated using hematoxylin and eosin (H&E) staining, electron microscopy, and terminal deoxynucleotidyl transferase-mediated nick-end labelling (TUNEL) staining. Oxidative stress markers, including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and total antioxidant capacity (T-AOC) were measured. Mitochondrial function was assessed by analysing peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), deacetylase sirtuin 1 (SIRT1), and proteins related to mitochondrial biogenesis and mitochondrial dynamics.

Results

Arsenic exposure significantly impaired learning and memory in rats, as evidenced by reduced performance in the MWM, whereas BAE treatment ameliorated these deficits. Furthermore, BAE alleviated arsenic-induced hippocampal neuronal apoptosis, as well as alleviating increased oxidative stress, weakened antioxidant capacity, and imbalanced mitochondrial biogenesis and dynamics. In this study, we focused on the core of mitochondrial quality control mechanism - mitochondrial biogenesis, fusion and fission. We explored the protective mechanism of BAE against arsenic - induced nerve damage. Based on these, we proposed an innovative therapeutic strategy: using natural products to target and regulate mitochondrial quality control.

Conclusion

This study indicated that BAE alleviates arsenic-induced neurotoxicity through its antioxidant and mitochondrial protective effects, effectively reducing arsenic-induced neurotoxicity and enhancing cognitive function.

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蓝莓花青素改善砷诱导的大鼠认知障碍：减轻线粒体损伤和失调

蓝莓花青素提取物（BAE）是一种天然抗氧化剂类黄酮，存在于蓝莓中，具有减轻氧化应激诱导的神经变性的潜力。先前的研究表明，BAE有可能减轻砷引起的认知障碍；然而，潜在的保护机制仍然难以捉摸。目的评价BAE减轻砷性认知障碍的作用，探讨BAE的神经保护作用是否与其抗氧化和线粒体保护作用有关。方法雄性大鼠60只，有或无BAE(100和200 mg/kg)，连续12周暴露于亚砷酸钠（NaAsO2, 10 mg/kg）。采用Morris水迷宫（MWM）评价大鼠的空间学习记忆能力。采用苏木精和伊红（H&；E）染色、电镜和末端脱氧核苷酸转移酶介导的镍端标记（TUNEL）染色评估大鼠海马神经元损伤。测定氧化应激标志物丙二醛（MDA）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GSH-Px）和总抗氧化能力（T-AOC）。通过分析过氧化物酶体增殖体激活受体γ辅助激活因子-1α (PGC-1α)、去乙酰化酶sirtuin 1 （SIRT1）以及与线粒体生物发生和线粒体动力学相关的蛋白质来评估线粒体功能。结果砷暴露显著损害了大鼠的学习和记忆能力，MWM的表现下降证明了这一点，而BAE治疗改善了这些缺陷。此外，BAE可减轻砷诱导的海马神经元凋亡，减轻氧化应激增加、抗氧化能力减弱以及线粒体生物发生和动力学失衡。在这项研究中，我们重点研究了线粒体质量控制机制的核心-线粒体的生物发生、融合和裂变。探讨BAE对砷致神经损伤的保护机制。基于这些，我们提出了一种创新的治疗策略：使用天然产物来靶向和调节线粒体质量控制。结论BAE通过其抗氧化和线粒体保护作用减轻砷致神经毒性，有效降低砷致神经毒性，增强认知功能。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.