Ellagic acid blocks activation of pancreatic stellate cells

Atsushi Masamune, Masahiro Satoh, Kazuhiro Kikuta, Noriaki Suzuki, Kennichi Satoh, Tooru Shimosegawa

Research output: Contribution to journalArticlepeer-review

86 Citations (Scopus)

Abstract

Activated pancreatic stellate cells (PSCs) play a pivotal role in the pathogenesis of pancreatic fibrosis and inflammation. Ellagic acid is a plant-derived polyphenol found in fruits and nuts, and has anti-oxidant and anti-inflammatory properties. But, little is known about the effects of ellagic acid on PSCs as well as on the activation of signal transduction pathways. We here evaluated the effects of ellagic acid on the activation and cell functions of PSCs. PSCs were isolated from rat pancreas tissue and used in their culture-activated, myofibroblast-like phenotype unless otherwise stated. Ellagic acid inhibited platelet-derived growth factor (PDGF)-BB-induced proliferation and migration, interleukin (IL)-1β- and tumor necrosis factor (TNF)-α-induced monocyte chemoattractant protein-1 production, and expression of α-smooth muscle actin and collagen genes. Ellagic acid inhibited PDGF-BB-induced tyrosine phosphorylation of PDGF β-receptor and the downstream activation of extracellular signal-regulated kinase and Akt. Ellagic acid inhibited IL-1β- and TNF-α-induced activation of activator protein-1 and mitogen-activated protein kinases (extracellular signal-regulated kinase, c-Jun N-terminal kinase and p38 mitogen-activated protein kinase), but not of nuclear factor-κB. In addition, ellagic acid inhibited transformation of freshly isolated cells to an activated, myofibroblast-like phenotype. In conclusion, ellagic acid inhibited key cell functions and activation of PSCs.

Original languageEnglish
Pages (from-to)869-878
Number of pages10
JournalBiochemical Pharmacology
Volume70
Issue number6
DOIs
Publication statusPublished - 2005 Sep 15

Keywords

  • MAP kinase
  • Pancreatic fibrosis
  • Pancreatic stellate cells
  • Pancreatitis
  • Platelet-derived growth factor
  • Polyphenol

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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