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Anti-inflammatory mechanism of lonchocarpine in LPS- or poly(I:C)-induced neuroinflammation

Title
Anti-inflammatory mechanism of lonchocarpine in LPS- or poly(I:C)-induced neuroinflammation
Authors
Jeong, Yeon-HuiPark, Jin-SunKim, Dong-HyunKang, Jihee LeeKim, Hee-Sun
Ewha Authors
이지희김희선박진선
SCOPUS Author ID
이지희scopus; 김희선scopus; 박진선scopus
Issue Date
2017
Journal Title
PHARMACOLOGICAL RESEARCH
ISSN
1043-6618JCR Link
Citation
vol. 119, pp. 431 - 442
Keywords
LonchocarpineMicrogliaNeuroinflammationLipopolysaccharidePoly(I:C)Molecular mechanism
Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Neuroinflammation plays an important role in the progression of various neurodegenerative diseases. In this study, we investigated the anti-inflammatory effects of lonchocarpine, a natural compound isolated from Abrus precatorius, under in vitro and in vivo neuroinflammatory conditions induced by challenge with lipopolysaccharide (LPS)- or polyinosinic-polycytidylic acid (poly(I:C)). Lonchocarpine suppressed the expression of iNOS and proinflammatory cytokines in LPS or poly(I:C)-stimulated BV2 microglial cells. These anti-inflammatory effects were verified in brains of mice with systemic inflammation induced by administration of LPS or poly(I:C). Lonchocarpine reduced the number of Iba-1-positive activated microglia, and suppressed the mRNA expression of various proinflammatory markers in the cortex of LPS- or poly(I:C)-injected mice. Molecular mechanistic experiments showed that lonchocarpine inhibited NF-kappa B activity by reducing the phosphorylation and degradation of I kappa B alpha in LPS- or poly(I:C)-stimulated BV2 cells. Analysis of further upstream signaling pathways in LPS-stimulated microglia showed that lonchocarpine inhibited the phosphorylation of I kappa B kinase and TGF beta-activated kinase 1 (TAK1). Moreover, lonchocarpine suppressed the interaction of myeloid differentiation factor 88 (MyD88) and intereleukin-1 receptor-associated kinase 4 (IRAK4). These data suggest that toll-like receptor 4 downstream signals such as MyD88/IRAK4-TAK1-NF-kappa B are at least partly involved in the anti-inflammatory mechanism of lonchocarpine in LPS-stimulated microglia. Its strong anti-inflammatory effects may make lonchocarpine an effective preventative drug for neuroinflammatory disorders that are associated with systemic inflammation. (C) 2017 Elsevier Ltd. All rights reserved.
DOI
10.1016/j.phrs.2017.02.027
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의과대학 > 의학과 > Journal papers
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