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Updated: Apr 27, 2026

Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Regulatory effects of fisetin on microglial activation
Jing-Yuan Chuang1, Pei-Chun Chang2, Yi-Chun Shen3
1Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 40402, Taiwan. jychuang@mail.cmu.edu.tw.
Abstract:
Increasing evidence suggests that inflammatory processes in the central nervous system that are mediated by microglial activation play a key role in neurodegeneration. Fisetin, a plant flavonol commonly found in fruits and vegetables, is frequently added to nutritional supplements due to its antioxidant properties. In the present study, treatment with fisetin inhibited microglial cell migration and ROS (reactive oxygen species) production. Treatment with fisetin also effectively inhibited LPS plus IFN-γ-induced nitric oxide (NO) production, and inducible nitric oxide synthase (iNOS) expression in microglial cells. Furthermore, fisetin also reduced expressions of iNOS and NO by stimulation of peptidoglycan, the major component of the Gram-positive bacterium cell wall. Fisetin also inhibited the enhancement of LPS/IFN-γ- or peptidoglycan-induced inflammatory mediator IL (interlukin)-1 β expression. Besides the antioxidative and anti-inflammatory effects of fisetin, our study also elucidates the manner in fisetin-induced an endogenous anti-oxidative enzyme HO (heme oxygenase)-1 expression. Moreover, the regulatory molecular mechanism of fisetin-induced HO-1 expression operates through the PI-3 kinase/AKT and p38 signaling pathways in microglia. Notably, fisetin also significantly attenuated inflammation-related microglial activation and coordination deficit in mice in vivo. These findings suggest that fisetin may be a candidate agent for the development of therapies for inflammation-related neurodegenerative diseases.
Insights
Fisetin, a plant flavonol, reduces microglial activation and inflammatory responses. This suggests fisetin may be a potential therapeutic agent for neurodegenerative diseases.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Microglial activation in the central nervous system is linked to neurodegeneration.
- Fisetin, a plant flavonol, possesses antioxidant properties and is found in fruits and vegetables.
Purpose of the Study:
- To investigate the anti-inflammatory and neuroprotective effects of fisetin on microglial cells.
- To elucidate the molecular mechanisms underlying fisetin's action.
Main Methods:
- In vitro studies using microglial cells treated with fisetin and inflammatory stimuli (LPS, IFN-γ, peptidoglycan).
- Assays for reactive oxygen species (ROS), nitric oxide (NO) production, inducible nitric oxide synthase (iNOS) expression, and interleukin-1β (IL-1β) expression.
- Analysis of heme oxygenase-1 (HO-1) expression and its regulatory pathways (PI-3 kinase/AKT, p38).
- In vivo studies in mice to assess fisetin's effect on microglial activation and coordination deficits.
Main Results:
- Fisetin inhibited microglial cell migration and ROS production.
- Fisetin suppressed LPS/IFN-γ- and peptidoglycan-induced NO production and iNOS expression.
- Fisetin reduced IL-1β expression and induced endogenous HO-1 expression via PI-3 kinase/AKT and p38 pathways.
- Fisetin attenuated inflammation-related microglial activation and coordination deficits in mice.
Conclusions:
- Fisetin exhibits significant anti-inflammatory and antioxidative effects in microglia.
- Fisetin modulates key signaling pathways involved in inflammation and oxidative stress.
- Fisetin demonstrates therapeutic potential for neurodegenerative diseases associated with neuroinflammation.
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