Flavonoids from Polypodium hastatum as neuroprotective agents attenuate cerebral ischemia/reperfusion injury in vitro and in vivo via activating Nrf2.

IF 5.2 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Redox Report Pub Date : 2025-12-01 Epub Date: 2024-12-19 DOI:10.1080/13510002.2024.2440204

Huankai Yao, Ruiqing Wu, Dan Du, Fengwei Ai, Feng Yang, Yan Li, Suhua Qi

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引用次数: 0

Abstract

Objectives: Cerebral ischemic stroke is a leading cause of death worldwide. Though timely reperfusion reduces the infarction size, it exacerbates neuronal apoptosis due to oxidative stress. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor regulating the expression of antioxidant enzymes. Activating Nrf2 gives a therapeutic approach to ischemic stroke.

Methods: Herein we explored flavonoids identified from Polypodium hastatum as Nrf2 activators and their protective effects on PC12 cells injured by oxygen and glucose deprivation/restoration (OGD/R) as well as middle cerebral artery occlusion (MCAO) mice.

Results: The results showed among these flavonoids, AAKR significantly improved the survival of PC12 cells induced by OGD/R and activated Nrf2 in a Keap1-dependent manner. Further investigations have disclosed AAKR attenuated oxidative stress, mitochondrial dysfunction and following apoptosis resulting from OGD/R. Meanwhile, activation of Nrf2 by AAKR was involved in the protective effects. Finally, it was found that AAKR could protect MCAO mice brains against ischemia/reperfusion injury via activating Nrf2.

Discussion: This investigation could provide lead compounds for the discovery of novel Nrf2 activators targeting ischemia/reperfusion injury.

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目的：脑缺血中风是导致全球死亡的主要原因。虽然及时再灌注能缩小梗死面积，但会加剧氧化应激导致的神经细胞凋亡。核因子红细胞2相关因子2（Nrf2）是一种调节抗氧化酶表达的转录因子。方法：我们在此探讨了从何首乌中鉴定出的黄酮类化合物作为Nrf2激活剂及其对缺氧和葡萄糖剥夺/恢复（OGD/R）损伤的PC12细胞以及大脑中动脉闭塞（MCAO）小鼠的保护作用：结果表明，在这些黄酮类化合物中，AAKR能明显改善PC12细胞在OGD/R诱导下的存活率，并以Keap1依赖的方式激活Nrf2。进一步的研究发现，AAKR 可减轻氧化应激、线粒体功能障碍以及 OGD/R 导致的细胞凋亡。同时，AAKR 对 Nrf2 的激活也参与了保护作用。最后，研究发现 AAKR 可通过激活 Nrf2 保护 MCAO 小鼠大脑免受缺血再灌注损伤：讨论：这项研究可为发现针对缺血再灌注损伤的新型 Nrf2 激活剂提供先导化合物。

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

Redox Report 生物-生化与分子生物学

CiteScore

6.10

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Redox Report is a multidisciplinary peer-reviewed open access journal focusing on the role of free radicals, oxidative stress, activated oxygen, perioxidative and redox processes, primarily in the human environment and human pathology. Relevant papers on the animal and plant environment, biology and pathology will also be included. While emphasis is placed upon methodological and intellectual advances underpinned by new data, the journal offers scope for review, hypotheses, critiques and other forms of discussion.