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

Yeon Hui Jeong, Jin Sun Park, Dong Hyun Kim, Jihee Lee Kang, Hee Sun Kim

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

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-κB activity by reducing the phosphorylation and degradation of IκBα 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 IκB kinase and TGFβ-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-κB 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.

Original languageEnglish
Pages (from-to)431-442
Number of pages12
JournalPharmacological Research
Volume119
DOIs
StatePublished - 1 May 2017

Keywords

  • Lipopolysaccharide
  • Lonchocarpine
  • Microglia
  • Molecular mechanism
  • Neuroinflammation
  • Poly(I:C)

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