Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Synthetic 3',4'-Dihydroxyflavone Exerts Anti-Neuroinflammatory Effects in BV2 Microglia and a Mouse Model

  • Kim, Namkwon (Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University) ;
  • Yoo, Hyung-Seok (Department of Pharmacy, College of Pharmacy, Kyung Hee University) ;
  • Ju, Yeon-Joo (Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University) ;
  • Oh, Myung Sook (Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University) ;
  • Lee, Kyung-Tae (Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University) ;
  • Inn, Kyung-Soo (Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University) ;
  • Kim, Nam-Jung (Department of Pharmacy, College of Pharmacy, Kyung Hee University) ;
  • Lee, Jong Kil (Department of Pharmacy, College of Pharmacy, Kyung Hee University)
  • Received : 2018.01.12
  • Accepted : 2018.01.23
  • Published : 2018.03.01
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Abstract

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 $E_2$ 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 $(NF)-{\kappa}B$ activation. This indicates that the anti-inflammatory activities of 3',4'-dihydroxyflavone might be related to suppression of the proinflammatory MAPK and $NF-{\kappa}B$ 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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References

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