Corylin inhibits LPS-induced inflammatory response and attenuates the activation of NLRP3 inflammasome in microglia

BMC Complement Altern Med. 2018 Aug 15;18(1):221. doi: 10.1186/s12906-018-2287-5.

Abstract

Background: Inflammation has been found to be associated with many neurodegenerative diseases, including Parkinson's and dementia. Attenuation of microglia-induced inflammation is a strategy that impedes the progression of neurodegenerative diseases.

Methods: We used lipopolysaccharide (LPS) to simulate murine microglia cells (BV2 cells) as an experimental model to mimic the inflammatory environment in the brain. In addition, we examined the anti-inflammatory ability of corylin, a main compound isolated from Psoralea corylifolia L. that is commonly used in Chinese herbal medicine. The production of nitric oxide (NO) by LPS-activated BV2 cells was measured using Griess reaction. The secretion of proinflammatory cytokines including tumor necrosis factor (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) by LPS-activated BV2 cells was analyzed using enzyme-linked immunosorbent assay (ELISA). The expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase-activation and recruitment domain (ASC), caspase-1, IL-1β and mitogen-activated protein kinases (MAPKs) in LPS-activated BV2 cells was examined by Western blot.

Results: Our experimental results demonstrated that corylin suppressed the production of NO and proinflammatory cytokines by LPS-activated BV2 cells. In addition, corylin inhibited the expression of iNOS and COX-2, attenuated the phosphorylation of ERK, JNK and p38, decreased the expression of NLRP3 and ASC, and repressed the activation of caspase-1 and IL-1β by LPS-activated BV2 cells.

Conclusion: Our results indicate the anti-inflammatory effects of corylin acted through attenuating LPS-induced inflammation and inhibiting the activation of NLRP3 inflammasome in LPS-activated BV2 cells. These results suggest that corylin might have potential in treating brain inflammation and attenuating the progression of neurodegeneration diseases.

Keywords: Anti-inflammation; Corylin; MAPK signaling pathway; Microglia; NLRP3 inflammasome.

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Flavonoids / pharmacology*
  • Inflammasomes / drug effects*
  • Inflammasomes / metabolism
  • Inflammation / chemically induced
  • Inflammation / metabolism
  • Lipopolysaccharides / adverse effects
  • Mice
  • Microglia / drug effects*
  • Microglia / metabolism
  • Mitogen-Activated Protein Kinases / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Phosphorylation / drug effects
  • Signal Transduction / drug effects

Substances

  • Flavonoids
  • Inflammasomes
  • Lipopolysaccharides
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • corylin
  • Mitogen-Activated Protein Kinases