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Resveratrol inhibits oligomeric Aβ-induced microglial activation via NADPH oxidase
1Department of Medical Chemistry, School of Basic Medical Science, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
Abstract:
Microglia‑mediated neuroinflammation is key in the pathogenesis of Alzheimer's disease (AD). Several studies have suggested that NADPH oxidase contributes to microglia‑mediated neuroinflammation. Resveratrol, which is a natural polyphenolic compound, exerts neuroprotective effects in AD due to its anti‑inflammatory properties. The present study aimed to investigate the effects of resveratrol on the activation of oligomeric amyloid β (oAβ)‑induced BV‑2 microglia, and to determine the role of NADPH oxidase in these effects. Microglial proliferation was measured by high‑content screening cell counting and using a bromodeoxyuridine incorporation assay. In addition, the levels of reactive oxygen species (ROS), nitric oxide (NO), tumor necrosis factor (TNF)‑α and interleukin (IL)‑1β were assessed. The results of the present study demonstrated that resveratrol inhibited the proliferation of oAβ‑induced microglia and the production of pro‑inflammatory factors, including ROS, NO, TNF‑α and IL‑1β. Subsequent mechanistic investigations demonstrated that resveratrol inhibited the oAβ‑induced mRNA and protein expression levels of p47phox and gp91phox. These results suggested that NADPH oxidase may be a potential target for AD treatment, and resveratrol may be a valuable natural product possessing therapeutic potential against AD.
Insights
Resveratrol reduces inflammation and cell growth in Alzheimer's disease models by inhibiting NADPH oxidase. This natural compound shows potential for treating neuroinflammation in Alzheimer's disease (AD).
Area of Science:
- Neuroscience
- Pharmacology
- Immunology
Background:
- Microglia-mediated neuroinflammation is central to Alzheimer's disease (AD) pathogenesis.
- NADPH oxidase is implicated in microglia activation and neuroinflammation.
- Resveratrol, a natural polyphenol, exhibits anti-inflammatory and neuroprotective properties relevant to AD.
Purpose of the Study:
- To investigate resveratrol's effects on oligomeric amyloid β (oAβ)-induced microglia activation.
- To elucidate the role of NADPH oxidase in resveratrol's anti-inflammatory actions in AD models.
Main Methods:
- BV-2 microglia treated with oAβ were analyzed for proliferation using cell counting and BrdU assays.
- Levels of reactive oxygen species (ROS), nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were measured.
- NADPH oxidase components (p47phox, gp91phox) mRNA and protein expression were assessed.
Main Results:
- Resveratrol significantly inhibited oAβ-induced microglia proliferation.
- Resveratrol suppressed the production of pro-inflammatory mediators (ROS, NO, TNF-α, IL-1β).
- Resveratrol reduced the expression of NADPH oxidase subunits p47phox and gp91phox.
Conclusions:
- Resveratrol mitigates microglia-mediated neuroinflammation in an AD context.
- NADPH oxidase is a key mediator of oAβ-induced microglia activation and a potential therapeutic target.
- Resveratrol demonstrates therapeutic potential for Alzheimer's disease due to its anti-inflammatory and NADPH oxidase inhibitory effects.
