Suppression of lipopolysaccharide-induced neuroinflammation by morin via MAPK, PI3K/Akt, and PKA/HO-1 signaling pathway modulation

Ji Sun Jung, Min Ji Choi, Yu Young Lee, Byung In Moon, Jin Sun Park, Hee Sun Kim

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

Morin is a flavonoid isolated from certain fruits and Chinese herbs and is known to possess various medicinal properties. In this study, we investigated the anti-inflammatory effects of morin on lipopolysaccharide (LPS)-induced microglial activation, both in vitro and in vivo. We found that morin inhibited inducible nitric oxide synthase (iNOS) and pro-inflammatory cytokines in LPS-stimulated BV2 microglial cells. Furthermore, morin suppressed the microglial activation and cytokine expression in the brains of LPS-stimulated mice. Subsequent mechanistic studies revealed that morin inhibited the action of LPSactivated mitogen- Activated protein kinases (MAPKs), protein kinase B (Akt) phosphorylation, nuclear factor-κB (NF-κB), and activating protein-1 (AP-1). Further, the phosphorylation and DNA binding activity of cAMP responsive element binding protein (CREB) was enhanced by morin. Moreover, morin suppressed the LPS-induced expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, while it increased heme oxygenase-1 (HO-1) expression and nuclear factor erythroid 2- related factor 2 (Nrf2) activation. Therefore, our data suggest that morin exerts anti-inflammatory effects in LPS-stimulated microglia by downregulating MAPK and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways while upregulating protein kinase A (PKA)/CREB and Nrf2/HO-1 signaling pathways.

Original languageEnglish
Pages (from-to)373-382
Number of pages10
JournalJournal of Agricultural and Food Chemistry
Volume65
Issue number2
DOIs
StatePublished - 18 Jan 2017

Keywords

  • Anti-inflammation
  • Microglia
  • Molecular mechanisms
  • Morin
  • Neuroinflammation

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