title: Regulatory effects of fisetin on microglial activation.
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.
authors: Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 40402, Taiwan. jychuang@mail.cmu.edu.tw.
authors: Jing-Yuan
authors: JY
authors: Chuang
authors: Department of Bioinformatics, Asia University, Taichung 41354, Taiwan. pcchang@asia.edu.tw.
authors: Pei-Chun
authors: PC
authors: Chang
authors: Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 40402, Taiwan. syciac@gmail.com.
authors: Yi-Chun
authors: YC
authors: Shen
authors: Department of Physiology, School of Medicine, China Medical University, Taichung 40402, Taiwan. clin33@mail.cmu.edu.tw.
authors: Chingju
authors: C
authors: Lin
authors: Department of Biotechnology, Asia University, Taichung 41354, Taiwan. tsaicf@asia.edu.tw.
authors: Cheng-Fang
authors: CF
authors: Tsai
authors: Department of General Surgery, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung 42743, Taiwan. guns5150@ms27.hinet.net.
authors: Jia-Hong
authors: JH
authors: Chen
authors: Department of Cell and Tissue Engineering, Changhua Christian Hospital, Changhua 500, Taiwan. ibizayeh0816@hotmail.com.
authors: Wei-Lan
authors: WL
authors: Yeh
authors: Graduate Institute of Basic Medical Science, China Medical University, Taichung 40402, Taiwan. lulu80620@yahoo.com.tw.
authors: Ling-Hsuan
authors: LH
authors: Wu
authors: Department of Life Sciences, National Chung Hsing University, Taichung 402, Taiwan. lingirl831@hotmail.com.
authors: Hsiao-Yun
authors: HY
authors: Lin
authors: Graduate Institute of Basic Medical Science, China Medical University, Taichung 40402, Taiwan. yushuliu220@gmail.com.
authors: Yu-Shu
authors: YS
authors: Liu
authors: Graduate Institute of Neural and Cognitive Sciences, China Medical University, Taichung 40402, Taiwan. dahyuu@mail.cmu.edu.tw.
authors: Dah-Yuu
authors: DY
authors: Lu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D005419:Flavonoids / Q000494:pharmacology*; D044948:Flavonols; D051547:Heme Oxygenase-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008813:Mice, Inbred ICR; D017628:Microglia / Q000187:drug effects / Q000276:immunology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000893:Anti-Inflammatory Agents; D005419:Flavonoids; D044948:Flavonols; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; C017875:fisetin