Natural polyphenol mangiferin delays neuronal cell senescence by inhibiting neuroinflammation mediated by microglial activation

作者：Wei Nong, Xiaoli Chen, Yixin Chen, Xueping Feng, Wen Kong, Rui Chi, Yan Li, Zhiquan Wei · 发表于：IBRO Neuroscience Reports · 年份：2025 · DOI：10.1016/j.ibneur.2025.04.006 · 被引用次数：5 · 研究领域：Mangiferin and Mango Extracts、Ginger and Zingiberaceae research、Adipokines, Inflammation, and Metabolic Diseases

Extracellular β-amyloid protein (Aβ) plaques are prominent pathological feature of Alzheimer's disease (AD). Aβ oligomers and plaques induce sustained microglial activation via the adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)/interferon regulatory factor 5 (IRF5) signaling pathway. This microglial activation-mediated neuroinflammation can accelerate neuronal cell senescence. Consequently, the regulation of the AMPK/mTOR/IRF5 pathway presents a potential therapeutic target for AD, as it may inhibit neuroinflammation and delay neuronal cell senescence. Mangiferin, a bioactive natural polyphenol extracted from the leaves of Mangifera indica Linn ., has garnered significant attention for its anti-inflammatory properties. However, it remains unclear whether mangiferin can modulate the AMPK/mTOR/IRF5 pathway to inhibit microglial activation-mediated neuroinflammation and delay neuronal cell senescence. This study employed both cellular and animal models of neuronal cell senescence to explore the effects of mangiferin on the regulation of the AMPK/mTOR/IRF5 pathway, aiming to inhibit neuroinflammation and delay neuronal cell senescence in vitro and in vivo . Specifically, SH-SY5Y neuroblastoma cells were subjected to a neuroinflammatory microenvironment induced by Aβ1–42-mediated HMC3 microglial activation to induce neuronal cell senescence in vitro . Additionally, SAMP8 accelerated aging mice were utilized as an aging animal model. Th...