Resveratrol Ameliorates the Severity of Fibrogenesis in Mice with Experimental Chronic Pancreatitis

Mol Nutr Food Res. 2018 Aug;62(16):e1700561. doi: 10.1002/mnfr.201700561. Epub 2018 Jan 4.

Abstract

Scope: Resveratrol is generally considered beneficial to health-span and longevity since this dietary stilbenoid has been scrutinized for its activating property on the "rescue gene" sirtuin-1 that promotes cellular survival under stress. In addition to its antiaging property, our previous in vitro studies revealed that resveratrol notably inhibits the production of extracellular matrix (ECM) proteins in pancreatic stellate cells (PSCs), the classic effector cells against pancreatic injury.

Objective: We aim to extrapolate resveratrol intervention to the management of fibrogenesis in mice with chronic pancreatitis.

Methods and results: C57/BL6 mice are given repetitive injections of cerulein (50 μg kg-1 h-1 ) for 6 weeks for the induction of chronic pancreatitis. We demonstrate that the oral administration of resveratrol (20 mg kg-1 d-1 ) effectively attenuated PSC activation, ECM deposition, fibrogenesis, and acinar atrophy in the pancreatitic parenchyma of cerulein-induced mice, as the damage index score was improved by 45.5%. The enhanced cell survival and preserved acinar integrity by resveratrol plausibly involves a perpetuated nuclear accumulation of Mist1 and a negative modulation of the Akt and p38 MAPK pathways.

Conclusion: We suggest that resveratrol is potentially a nutraceutical for the mitigations of pancreatic fibrosis in chronic pancreatitis for which no effective therapeutic measure is currently available.

Keywords: chronic pancreatitis; pancreatic fibrosis; pancreatic stellate cells; resveratrol; stilbenoid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Apoptosis
  • Carrier Proteins / genetics
  • Cell Survival / drug effects
  • Cells, Cultured
  • Extracellular Matrix / metabolism
  • Fibrosis
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
  • Pancreas / pathology*
  • Pancreatic Stellate Cells / drug effects
  • Pancreatitis, Chronic / drug therapy*
  • Proto-Oncogene Proteins c-akt / genetics
  • Resveratrol / therapeutic use*
  • p38 Mitogen-Activated Protein Kinases / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Clnk protein, mouse
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Proto-Oncogene Proteins c-akt
  • p38 Mitogen-Activated Protein Kinases
  • Resveratrol