KMID : 0606920180260020210
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Biomolecules & Therapeutics 2018 Volume.26 No. 2 p.210 ~ p.217
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Synthetic 3¡¯,4¡¯-Dihydroxyflavone Exerts Anti-Neuroinflammatory Effects in BV2 Microglia and a Mouse Model
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Kim Nam-Kwon
Yoo Hyung-Seok Ju Yeon-Joo Oh Myung-Sook Lee Kyung-Tae Inn Kyung-Soo Kim Nam-Jung Lee Jong-Kil
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Abstract
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Neuroinflammation is an immune response within the central nervous system against various proinflammatory stimuli. Abnormal activation of this response contributes to neurodegenerative diseases such as Parkinson disease, Alzheimer¡¯s disease, and Huntington disease. Therefore, pharmacologic modulation of abnormal neuroinflammation is thought to be a promising approach to amelioration of neurodegenerative diseases. In this study, we evaluated the synthetic flavone derivative 3¡¯,4¡¯-dihydroxyflavone, investigating its anti-neuroinflammatory activity in BV2 microglial cells and in a mouse model. In BV2 microglial cells, 3¡¯,4¡¯-dihydroxyflavone successfully inhibited production of chemokines such as nitric oxide and prostaglandin E2 and proinflammatory cytokines such as tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 in BV2 microglia. It also inhibited phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-¥êB activation. This indicates that the anti-inflammatory activities of 3¡¯,4¡¯-dihydroxyflavone might be related to suppression of the proinflammatory MAPK and NF-¥êB signaling pathways. Similar anti-neuroinflammatory activities of the compound were observed in the mouse model. These findings suggest that 3¡¯,4¡¯-dihydroxyflavone is a potential drug candidate for the treatment of microglia-related neuroinflammatory diseases.
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KEYWORD
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Microglia, Neuroinflammation, Lipopolysaccharide, BV2 microglia, Flavone
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