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Molecules 2014, 19(7), 8820-8839;

Regulatory Effects of Fisetin on Microglial Activation

Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 40402, Taiwan
Department of Bioinformatics, Asia University, Taichung 41354, Taiwan
Department of Physiology, School of Medicine, China Medical University, Taichung 40402, Taiwan
Department of Biotechnology, Asia University, Taichung 41354, Taiwan
Department of General Surgery, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung 42743, Taiwan
Department of Cell and Tissue Engineering, Changhua Christian Hospital, Changhua 500, Taiwan
Graduate Institute of Basic Medical Science, China Medical University, Taichung 40402, Taiwan
Department of Life Sciences, National Chung Hsing University, Taichung 402, Taiwan
Graduate Institute of Neural and Cognitive Sciences, China Medical University, Taichung 40402, Taiwan
Department of Photonics and Communication Engineering at Asia University, Taichung 41354, Taiwan
These authors contributed equally to this work.
Author to whom correspondence should be addressed.
Received: 30 April 2014 / Revised: 13 June 2014 / Accepted: 18 June 2014 / Published: 26 June 2014
(This article belongs to the Special Issue Natural Antioxidants and Ageing)
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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. View Full-Text
Keywords: microglia; neuroinflammation; neurodegeneration; fisetin; cytokine microglia; neuroinflammation; neurodegeneration; fisetin; cytokine

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Chuang, J.-Y.; Chang, P.-C.; Shen, Y.-C.; Lin, C.; Tsai, C.-F.; Chen, J.-H.; Yeh, W.-L.; Wu, L.-H.; Lin, H.-Y.; Liu, Y.-S.; Lu, D.-Y. Regulatory Effects of Fisetin on Microglial Activation. Molecules 2014, 19, 8820-8839.

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