KMID : 0606920210290020127
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Biomolecules & Therapeutics 2021 Volume.29 No. 2 p.127 ~ p.134
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Antineuroinflammatory Effects of 7,3¡¯,4¡¯-Trihydroxyisoflavone in Lipopolysaccharide-Stimulated BV2 Microglial Cells through MAPK and NF-¥êB Signaling Suppression
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Kim Seon-Kyung
Ko Yong-Hyun Lee You-Young Lee Seok-Yong Jang Choon-Gon
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Abstract
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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-3¥â (GSK-3¥â), and nuclear factor kappa B (NF-¥êB). Overall, 7,3¡¯,4¡¯-THIF exerts antineuroinflammatory effects against LPS-induced microglial activation by suppressing mitogen-activated protein kinase (MAPK) and NF-¥êB signaling, ultimately reducing proinflammatory responses. Therefore, these antineuroinflammatory effects of 7,3¡¯,4¡¯-THIF suggest its potential as a therapeutic agent for neurodegenerative disorders.
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KEYWORD
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7,3¡¯,4¡¯-Trihydroxyisoflavone, Neuroinflammation, BV2 microglial cells, Lipopolysaccharide, Mitogen-activated protein kinase, Nuclear factor kappa B
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