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Published on: January 30, 2014
Natural polyphenol mangiferin delays neuronal cell senescence by inhibiting neuroinflammation mediated by microglial
Wei Nong1, Xiaoli Chen2, Yixin Chen3
1Guangxi Scientific Research Center of Traditional Chinese Medicine, Guangxi Traditional Chinese Medicine University, Nanning 530200, China.
Abstract:
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. The results indicate that mangiferin significantly enhances AMPK phosphorylation in microglial cells, inhibits mTOR activation, and downregulates IRF5 expression. These effects collectively suppress microglial activation and markedly reduce the production of pro-inflammatory cytokines by activated microglia. Consequently, there is a decrease in the proportion of neurons arrested in the G0/G1 phase and a reduction in the number of senescence-associated β-galactosidase (SA-β-gal) positive neurons. Furthermore, mangiferin significantly decreases the expression of neuronal cell senescence markers P16Ink4a and P21Cip1. Collectively, these findings suggest that mangiferin effectively regulates the AMPK/mTOR/IRF5 pathway, inhibits neuroinflammation mediated by microglial activation, and delays neuronal cell senescence. This study underscores the potential of mangiferin for the treatment of neuroinflammation and neurodegenerative diseases.
Insights
Mangiferin, a natural compound, inhibits neuroinflammation and delays brain cell aging by regulating the AMPK/mTOR/IRF5 pathway. This suggests potential for treating Alzheimer's disease and other neurodegenerative conditions.
Area of Science:
- Neuroscience
- Pharmacology
- Cellular Biology
Background:
- Alzheimer's disease (AD) is characterized by extracellular beta-amyloid (Aβ) plaques.
- Aβ-induced microglial activation via the AMPK/mTOR/IRF5 pathway drives neuroinflammation and neuronal senescence.
- Targeting this pathway offers a potential therapeutic strategy for AD.
Purpose of the Study:
- To investigate mangiferin's effect on the AMPK/mTOR/IRF5 pathway in neuroinflammation and neuronal senescence.
- To evaluate mangiferin's potential as a therapeutic agent for neurodegenerative diseases.
Main Methods:
- Utilized cellular models (SH-SY5Y neuroblastoma cells with Aβ1-42-induced microglial activation) and an animal model (SAMP8 mice).
- Assessed mangiferin's impact on AMPK/mTOR/IRF5 signaling, microglial activation, pro-inflammatory cytokine production, and neuronal senescence markers (G0/G1 arrest, SA-β-gal, P16Ink4a, P21Cip1).
Main Results:
- Mangiferin enhanced AMPK phosphorylation, inhibited mTOR activation, and downregulated IRF5 expression in microglial cells.
- Mangiferin suppressed microglial activation, reduced pro-inflammatory cytokine release, and decreased neuronal senescence markers.
- Observed decreased G0/G1 phase arrest and fewer SA-β-gal positive neurons, alongside reduced P16Ink4a and P21Cip1 expression.
Conclusions:
- Mangiferin effectively modulates the AMPK/mTOR/IRF5 pathway, inhibiting microglial activation-mediated neuroinflammation.
- Mangiferin demonstrates a neuroprotective effect by delaying neuronal cell senescence.
- These findings highlight mangiferin's therapeutic potential for neuroinflammation and neurodegenerative diseases like AD.
