Silymarin Attenuates the Severity of Cerulein-Induced Acute Pancreatitis

Pancreas. 2020 Jan;49(1):89-95. doi: 10.1097/MPA.0000000000001453.

Abstract

Objectives: In this study, we investigated the anti-inflammatory effects of silymarin on cerulein-induced acute pancreatitis (AP) in mice.

Methods: Cerulein (50 μg/kg) was injected intraperitoneally once hourly for 6 hours to induce AP. To investigate the prophylactic effects of silymarin, dimethyl sulfoxide or silymarin (25, 50, and 100 mg/kg) was injected intraperitoneally 1 hour before cerulein injection. To investigate the therapeutic effects of silymarin, dimethyl sulfoxide or silymarin (100 mg/kg) was injected intraperitoneally 1, 3, or 5 hours after the first cerulein injection. Blood, pancreas, and lungs were harvested 6 hours after the last cerulein injection.

Results: Pre- and posttreatment with silymarin decreased the pancreas weight/body weight ratio and serum amylase activity. Furthermore, silymarin treatment inhibited pancreas and lung injury and neutrophil infiltration during cerulein-induced AP. In addition, silymarin inhibited increased secretion of proinflammatory cytokines such as interleukin 1β, interleukin 6, and tumor necrosis factor α. Finally, mitogen-activated protein kinases (MAPKs) and nuclear factor-κB were activated by cerulein, and only p38 in MAPK was inhibited by silymarin.

Conclusions: These findings suggest that silymarin attenuates the severity of AP through inhibition of p38 MAPKs and that silymarin could be a potential prophylactic and therapeutic agent for the treatment of AP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Amylases / blood
  • Animals
  • Antioxidants / administration & dosage
  • Antioxidants / pharmacology
  • Ceruletide
  • Cytokines / metabolism
  • Inflammation Mediators / metabolism
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism
  • Organ Size / drug effects
  • Pancreas / drug effects*
  • Pancreas / metabolism
  • Pancreas / pathology
  • Pancreatitis / chemically induced
  • Pancreatitis / metabolism
  • Pancreatitis / prevention & control*
  • Protective Agents / administration & dosage
  • Protective Agents / pharmacology
  • Severity of Illness Index*
  • Silymarin / administration & dosage
  • Silymarin / pharmacology*

Substances

  • Antioxidants
  • Cytokines
  • Inflammation Mediators
  • NF-kappa B
  • Protective Agents
  • Silymarin
  • Ceruletide
  • Mitogen-Activated Protein Kinases
  • Amylases