Centipedegrass extracts regulate LPS-mediated aberrant immune responses by inhibiting Janus kinase

Phytomedicine. 2019 Mar 1:55:172-178. doi: 10.1016/j.phymed.2018.06.039. Epub 2018 Aug 19.

Abstract

Background: Centipedegrass extract (CGE) is rich in several polyphenolic compounds including C-glycosylflavonoids, such as maysin and its derivatives, and exerts antioxidant, anti-adipogenic and anticancer effects. However, the effect of CGE on the immune system is unclear.

Purpose: CGE might inhibit NO production induced by lipopolysaccharide (LPS). In this study, we propose a molecular mechanism for regulation of aberrant immune responses by CGE in LPS-stimulated RAW264.7 cells.

Study design: We will preparation of Centipedegrass extract and purify partially in rich of maysin and its derivatives. And examine the effect of the CGE on immune system using LPS-induced RAW cells and animals.

Methods: LPS-induced nitric oxide (NO) and interleukin-6 levels were measured by enzyme-linked immunosorbent assay. The mRNA and protein levels of immune mediators were analyzed by reverse-transcription polymerase chain reaction and immunoblotting, respectively.

Results: CGE inhibited LPS-induced NO production in a concentration-dependent manner by suppressing inducible nitric oxide synthase (iNOS) expression in LPS-stimulated cells; this effect was mediated by inhibition of the JAK/STAT pathway. However, CGE did not regulate the expression of other factors, including phosphorylated p38, c-jun N-terminal kinase, or extracellular signal-regulated kinase 1/2. In addition, CGE increased T cells percentage in peripheral blood after oral administration.

Conclusion: These results indicate that CGE suppresses LPS-induced production of NO and expression of iNOS by directly inhibiting JAK2 kinase activity and enhancing effects on the immune system in mice.

Keywords: Centipedegrass extract; JAK/STAT; NO; iNOS.

MeSH terms

  • Administration, Oral
  • Animals
  • Dose-Response Relationship, Drug
  • Janus Kinase 2 / metabolism
  • Janus Kinase Inhibitors / immunology
  • Janus Kinase Inhibitors / pharmacology*
  • Lipopolysaccharides / toxicity
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinases / metabolism
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / antagonists & inhibitors
  • Nitric Oxide Synthase Type II / metabolism
  • Phosphorylation / drug effects
  • Plant Extracts / administration & dosage
  • Plant Extracts / immunology*
  • Plant Extracts / pharmacology*
  • Poaceae / chemistry*
  • RAW 264.7 Cells

Substances

  • Janus Kinase Inhibitors
  • Lipopolysaccharides
  • Plant Extracts
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Jak2 protein, mouse
  • Janus Kinase 2
  • Mitogen-Activated Protein Kinases