Bergapten prevents lipopolysaccharide-induced inflammation in RAW264.7 cells through suppressing JAK/STAT activation and ROS production and increases the survival rate of mice after LPS challenge

Int Immunopharmacol. 2017 Jul:48:159-168. doi: 10.1016/j.intimp.2017.04.026. Epub 2017 May 14.

Abstract

Bergapten (BG) is a cumarine-derivate compound in many medicinal plants. Here, in vitro and in vivo experimental results indicated that BG possesses anti-inflammatory properties, Based on this, we further investigated the precise molecular mechanisms of BG in LPS-stimulated inflammation response. Studies revealed that BG inhibited LPS-stimulated productions of TNF-α, IL-1β, IL-6, PGE2 and NO as well as the expression of iNOS and COX-2, and at the same time, it increased LPS-induced release of IL-10 in a dose-dependent manner in RAW264.7 cells. Mechanistically, BG suppressed the activations of JAK/STAT, but not that of MAPKs and NF-κB. In addition, BG, as an antioxidant, prevented the accumulation of ROS, which further exerted its anti-inflammatory function. In vivo researches revealed that BG decreased LPS-induced mortality in mice. In conclusions, BG may be a potential candidate for inflammation therapy via inhibiting JAK/STAT activation and ROS production in RAW264.7 cells.

Keywords: Bergapten; Inflammation; JAK/STAT; ROS.

MeSH terms

  • 5-Methoxypsoralen
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Cell Survival / drug effects
  • Cyclooxygenase 2 / metabolism
  • Cytokines / metabolism
  • Janus Kinase 1 / metabolism
  • Janus Kinase 2 / metabolism
  • Lipopolysaccharides
  • Male
  • Methoxsalen / analogs & derivatives*
  • Methoxsalen / pharmacology
  • Methoxsalen / therapeutic use
  • Mice
  • Mice, Inbred ICR
  • Nitric Oxide Synthase Type II / metabolism
  • RAW 264.7 Cells
  • Reactive Oxygen Species / metabolism
  • STAT1 Transcription Factor / metabolism
  • STAT3 Transcription Factor / metabolism
  • Shock / drug therapy

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Lipopolysaccharides
  • Reactive Oxygen Species
  • STAT1 Transcription Factor
  • STAT3 Transcription Factor
  • Stat1 protein, mouse
  • Stat3 protein, mouse
  • 5-Methoxypsoralen
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Jak1 protein, mouse
  • Jak2 protein, mouse
  • Janus Kinase 1
  • Janus Kinase 2
  • Methoxsalen