Frontiers in pharmacology · 2025
Mangiferin mitigates neurological deficits and ferroptosis via NRF2/ARE pathway activation in cerebral ischemia-reperfusion rats.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Peng Chenjia, Zhang Yang, Chai Jiaqing, Zhang Hengbo
Аннотация
INTRODUCTION: Ferroptosis is a newly described form of nonapoptotic, iron-dependent cell death that plays an essential role in the pathogenesis of ischemic stroke. Targeting ferroptosis may be an effective way to treat ischemic stroke. Mangiferin (MGF) is a natural polyphenol that has been shown to protect neurological function via multiple mechanisms. However, the mechanism by which MGF inhibits ferroptosis in stroke remains unclear.
METHODS: An ischemic stroke rat model was established by middle cerebral artery occlusion. Neurological scoring, TTC staining, behavioral tests, Nissl staining, HE staining and immunochemistry were used to analyze the influences of MGF on neurological deficits, the infarct area, cognitive function, neuronal morphology, histopathological injury, and the morphology of microglia and astrocytes. Transmission electron microscopy and Perls' stain were used to evaluate the characteristics of ferroptosis. Western blotting was used to analyze the expression of NRF2, FTL, SLC7A11 and GPX4. ELISA was used to analyze the levels of cytokines, including IL-6, IL-1β and TNF-α, to evaluate neuroinflammation. Oxidative stress was evaluated by analyzing the levels of ROS, MDA, GSH, and SOD.
RESULTS: MGF clearly improved the neurological function and learning and memory ability of stroke rats. MGF significantly decreased ROS and MDA and increased GSH, SOD. MGF significantly suppressed neuroinflammation by downregulating IL-6, IL-1β and TNF-α. Ferroptosis in stroke rats was significantly inhibited by MGF. MGF significantly increased the expression of NRF2, FTL, SLC7A11 and GPX4. The NRF2 inhibitor ML385 significantly reversed the effects of MGF on stroke rats.
CONCLUSION: MGF protects neurological function and suppresses ferroptosis via activating NRF2/ARE pathway in ischemic stroke rats.
METHODS: An ischemic stroke rat model was established by middle cerebral artery occlusion. Neurological scoring, TTC staining, behavioral tests, Nissl staining, HE staining and immunochemistry were used to analyze the influences of MGF on neurological deficits, the infarct area, cognitive function, neuronal morphology, histopathological injury, and the morphology of microglia and astrocytes. Transmission electron microscopy and Perls' stain were used to evaluate the characteristics of ferroptosis. Western blotting was used to analyze the expression of NRF2, FTL, SLC7A11 and GPX4. ELISA was used to analyze the levels of cytokines, including IL-6, IL-1β and TNF-α, to evaluate neuroinflammation. Oxidative stress was evaluated by analyzing the levels of ROS, MDA, GSH, and SOD.
RESULTS: MGF clearly improved the neurological function and learning and memory ability of stroke rats. MGF significantly decreased ROS and MDA and increased GSH, SOD. MGF significantly suppressed neuroinflammation by downregulating IL-6, IL-1β and TNF-α. Ferroptosis in stroke rats was significantly inhibited by MGF. MGF significantly increased the expression of NRF2, FTL, SLC7A11 and GPX4. The NRF2 inhibitor ML385 significantly reversed the effects of MGF on stroke rats.
CONCLUSION: MGF protects neurological function and suppresses ferroptosis via activating NRF2/ARE pathway in ischemic stroke rats.