Journal of ginseng research · 2025
Ginsenoside Re mitigates Aβ1-42-induced neurotoxicity by promoting autophagy and suppressing NLRP3 inflammasome.
СтатьяНазвание и аннотация: Перевод в очереди
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.
Madhi Iskander, Kim Ji-Hee, Shin Hyun Seung, So Yun Hee, Jung Eui-Man, Kim YoungHee
Аннотация
BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by β-amyloid (Aβ) accumulation and neuroinflammation. Activation of NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome in microglia significantly contributes to AD-associated neuroinflammation and neuronal damage. Ginsenoside Re (G-Re), a major bioactive constituent of Panax ginseng, exhibits anti-inflammatory properties, but its role in modulating inflammasome activation in AD remains unclear.
METHODS: This study evaluated the therapeutic potential of G-Re in mice intracerebroventricularly injected with Aβ1-42 and delineated its molecular mechanisms in complementary cell-based models. We employed behavioral testing, immunohistochemistry, Western blotting, enzyme-linked immunosorbent assays, Annexin V apoptosis assays, and mitochondrial functional assays.
RESULTS: Intraperitoneal administration of G-Re significantly improved cognitive performance, as evidenced by enhanced outcomes in the T-maze and novel object recognition tests. G-Re treatment reduced microglial activation and interleukin-1β (IL-1β) levels in the cortex and hippocampus. In vitro, G-Re protected neurons from conditioned medium derived from Aβ1-42-stimulated microglia, showing neuroprotection comparable to anti-IL-1β treatment. G-Re also inhibited Aβ1-42-induced activation of the NLRP3 inflammasome, as indicated by diminished levels of NLRP3, cleaved caspase-1, cleaved gasdermin D (GSDMD), IL-1β, and IL-18 in brain tissues and cultured microglia. Mechanistically, G-Re reduced mitochondrial reactive oxygen species (mtROS), preserved mitochondrial membrane potential, and activated autophagy via SIRT1/AMPK/mTOR signaling, thereby suppressing inflammasome activation.
CONCLUSION: G-Re ameliorates Aβ1-42-induced neuroinflammation and cognitive impairment by restoring mitochondrial homeostasis, enhancing autophagy, and suppressing NLRP3 inflammasome activation. These findings suggest G-Re as a potential therapeutic intervention for neurodegenerative disorders including AD.
METHODS: This study evaluated the therapeutic potential of G-Re in mice intracerebroventricularly injected with Aβ1-42 and delineated its molecular mechanisms in complementary cell-based models. We employed behavioral testing, immunohistochemistry, Western blotting, enzyme-linked immunosorbent assays, Annexin V apoptosis assays, and mitochondrial functional assays.
RESULTS: Intraperitoneal administration of G-Re significantly improved cognitive performance, as evidenced by enhanced outcomes in the T-maze and novel object recognition tests. G-Re treatment reduced microglial activation and interleukin-1β (IL-1β) levels in the cortex and hippocampus. In vitro, G-Re protected neurons from conditioned medium derived from Aβ1-42-stimulated microglia, showing neuroprotection comparable to anti-IL-1β treatment. G-Re also inhibited Aβ1-42-induced activation of the NLRP3 inflammasome, as indicated by diminished levels of NLRP3, cleaved caspase-1, cleaved gasdermin D (GSDMD), IL-1β, and IL-18 in brain tissues and cultured microglia. Mechanistically, G-Re reduced mitochondrial reactive oxygen species (mtROS), preserved mitochondrial membrane potential, and activated autophagy via SIRT1/AMPK/mTOR signaling, thereby suppressing inflammasome activation.
CONCLUSION: G-Re ameliorates Aβ1-42-induced neuroinflammation and cognitive impairment by restoring mitochondrial homeostasis, enhancing autophagy, and suppressing NLRP3 inflammasome activation. These findings suggest G-Re as a potential therapeutic intervention for neurodegenerative disorders including AD.