Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Antineuroinflammatory Effects of 7,3',4'-Trihydroxyisoflavone in Lipopolysaccharide-Stimulated BV2 Microglial Cells through MAPK and NF-κB Signaling Suppression

  • Kim, Seon-Kyung (Department of Pharmacology, School of Pharmacy, Sungkyunkwan University) ;
  • Ko, Yong-Hyun (Department of Pharmacology, School of Pharmacy, Sungkyunkwan University) ;
  • Lee, Youyoung (Department of Pharmacology, School of Pharmacy, Sungkyunkwan University) ;
  • Lee, Seok-Yong (Department of Pharmacology, School of Pharmacy, Sungkyunkwan University) ;
  • Jang, Choon-Gon (Department of Pharmacology, School of Pharmacy, Sungkyunkwan University)
  • Received : 2020.05.25
  • Accepted : 2020.07.24
  • Published : 2021.03.01
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Abstract

Neuroinflammation―a common pathological feature of neurodegenerative disorders such as Alzheimer's disease―is mediated by microglial activation. Thus, inhibiting microglial activation is vital for treating various neurological disorders. 7,3',4'-Trihydroxyisoflavone (THIF)―a secondary metabolite of the soybean compound daidzein―possesses antioxidant and anticancer properties. However, the effects of 7,3',4'-THIF on microglial activation have not been explored. In this study, antineuroinflammatory effects of 7,3',4'-THIF in lipopolysaccharide (LPS)-stimulated BV2 microglial cells were examined. 7,3',4'-THIF significantly suppressed the production of the proinflammatory mediators nitric oxide (NO), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) as well as of the proinflammatory cytokine interleukin-6 (IL-6) in LPS-stimulated BV2 microglial cells. Moreover, 7,3',4'-THIF markedly inhibited reactive oxygen species (ROS) generation. Western blotting revealed that 7,3',4'-THIF diminished LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), glycogen synthase kinase-3β (GSK-3β), and nuclear factor kappa B (NF-κB). Overall, 7,3',4'-THIF exerts antineuroinflammatory effects against LPS-induced microglial activation by suppressing mitogen-activated protein kinase (MAPK) and NF-κB signaling, ultimately reducing proinflammatory responses. Therefore, these antineuroinflammatory effects of 7,3',4'-THIF suggest its potential as a therapeutic agent for neurodegenerative disorders.

Keywords

References

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