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Anti-inflammatory mechanism of lonchocarpine in LPS- or poly(I:C)-induced neuroinflammation
- Anti-inflammatory mechanism of lonchocarpine in LPS- or poly(I:C)-induced neuroinflammation
- Jeong, Yeon-Hui; Park, Jin-Sun; Kim, Dong-Hyun; Kang, Jihee Lee; Kim, Hee-Sun
- Ewha Authors
- 이지희; 김희선; 박진선
- SCOPUS Author ID
- 이지희; 김희선; 박진선
- Issue Date
- Journal Title
- PHARMACOLOGICAL RESEARCH
- vol. 119, pp. 431 - 442
- Lonchocarpine; Microglia; Neuroinflammation; Lipopolysaccharide; Poly(I:C); Molecular mechanism
- ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
- SCI; SCIE; SCOPUS
- 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.
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