Ellagic acid blocks activation of pancreatic stellate cells.
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)-1beta- and tumor necrosis factor (TNF)-alpha-induced monocyte chemoattractant protein-1 production, and expression of alpha-smooth muscle actin and collagen genes. Ellagic acid inhibited PDGF-BB-induced tyrosine phosphorylation of PDGF beta-receptor and the downstream activation of extracellular signal-regulated kinase and Akt. Ellagic acid inhibited IL-1beta- and TNF-alpha-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-kappaB. 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.
Masamune
Atsushi
A
Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan. amasamune@int3.med.tohoku.ac.jp
Satoh
Masahiro
M
Kikuta
Kazuhiro
K
Suzuki
Noriaki
N
Satoh
Kennichi
K
Shimosegawa
Tooru
T
D000818:Animals; D001483:Base Sequence; D000077214:Becaplermin; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D004610:Ellagic Acid / Q000494:pharmacology*; D008297:Male; D010179:Pancreas / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors / Q000502:physiology; D016133:Polymerase Chain Reaction; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017208:Rats, Wistar
C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D017931:DNA Primers; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D004610:Ellagic Acid; D000077214:Becaplermin