Open AccessAntineuroinflammatory Effects of 7,3’,4’-Trihydroxyisoflavone in Lipopolysaccharide-Stimulated BV2 Microglial Cells through MAPK and NF-κB Signaling Suppression
Author(s) -
SeonKyung Kim,
Youngjoong Ko,
Youyoung Lee,
SeokYong Lee,
ChoonGon Jang
Publication year - 2021
Publication title -
biomolecules and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.977
H-Index - 36
eISSN - 2005-4483
pISSN - 1976-9148
DOI - 10.4062/biomolther.2020.093
Subject(s) - lipopolysaccharide , nf κb , mapk/erk pathway , microglia , inflammation , medicine , signal transduction , pharmacology , neuroscience , cancer research , chemistry , microbiology and biotechnology , biology
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.