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http://dx.doi.org/10.4062/biomolther.2020.093

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)
Publication Information
Biomolecules & Therapeutics / v.29, no.2, 2021 , pp. 127-134 More about this Journal
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
7,3',4'-Trihydroxyisoflavone; Neuroinflammation; BV2 microglial cells; Lipopolysaccharide; Mitogen-activated protein kinase; Nuclear factor kappa B;
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