Fisetin attenuates cerulein-induced acute pancreatitis through down regulation of JNK and NF-κB signaling pathways

Eur J Pharmacol. 2014 Aug 15:737:149-58. doi: 10.1016/j.ejphar.2014.05.018. Epub 2014 May 24.

Abstract

Acute pancreatitis (AP) is a complicated disease which is largely undiscovered. Fisetin, a natural flavonoid from fruits and vegetables, has been shown to have anti-inflammatory, antioxidant, and anti-cancer activities in various disease models. However, the effects of fisetin on AP have not been determined. Pre- and post- treatment of mice with fisetin reduced the severity of AP and pancreatitis-associated lung injury and inhibited several biochemical parameters (pancreatic weight to body weight ratio, amylase, lipase, and myeloperoxidase activity) and production of inflammatory cytokines. In pancreatic acinar cells, fisetin also inhibited cell death and production of inflammatory cytokines. In addition, fisetin inhibited activation of c-Jun NH2-terminal kinase (JNK) and nuclear factor (NF)-κB in vivo and in vitro. In conclusion, these results suggest that fisetin exhibits anti-inflammatory effect on AP and could be a beneficial agent in the treatment of AP and its pulmonary complications.

Keywords: Acinar cells; Acute pancreatitis; Fisetin; Proinflammatory cytokines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinar Cells / drug effects
  • Acinar Cells / pathology
  • Acute Disease
  • Administration, Oral
  • Animals
  • Ceruletide / adverse effects*
  • Down-Regulation / drug effects*
  • Enzyme Activation / drug effects
  • Female
  • Flavonoids / administration & dosage
  • Flavonoids / pharmacology*
  • Flavonoids / therapeutic use
  • Flavonols
  • Injections, Intraperitoneal
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Lung / drug effects
  • Lung / pathology
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism*
  • Pancreas / drug effects
  • Pancreas / pathology
  • Pancreatitis / chemically induced
  • Pancreatitis / drug therapy
  • Pancreatitis / pathology*
  • Pancreatitis / prevention & control
  • Signal Transduction / drug effects*

Substances

  • Flavonoids
  • Flavonols
  • NF-kappa B
  • Ceruletide
  • JNK Mitogen-Activated Protein Kinases
  • fisetin