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Green tea polyphenol (–)‐epigallocatechin‐3‐gallate inhibits ethanol‐induced activation of pancreatic stellate cells
Author(s) -
Asaumi H.,
Watanabe S.,
Taguchi M.,
Tashiro M.,
Nagashio Y.,
Nomiyama Y.,
Nakamura H.,
Otsuki M.
Publication year - 2006
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.2006.01599.x
Subject(s) - hepatic stellate cell , oxidative stress , chemistry , cytoprotection , biochemistry , antioxidant , epigallocatechin gallate , superoxide dismutase , myofibroblast , lipid peroxidation , fibrosis , endocrinology , polyphenol , medicine , biology
Background Activated pancreatic stellate cells (PSCs) play a central role in the pathogenesis of pancreatic fibrogenesis and inflammation. Ethanol, a major cause of chronic pancreatitis, directly induces PSC activation and oxidative stress. Inhibition of PSC activation or stimulation to PSC might be an effective therapeutic strategy for the prevention of pancreatic fibrosis, and (–)‐epigallocatechin‐3‐gallate (EGCG), a major component of green tea extracts, is a potent antioxidant of polyphenols. Therefore, we examined the mechanisms through which ethanol induces oxidative stress on PSCs and evaluated the effect of EGCG on activation and cell functions of ethanol‐stimulated PSCs. Materials and methods The PSCs were isolated from the pancreas of male Wister rats with Nycodenz gradient methods and cells between passages one and four were used. Isolated PSCs were cultured with ethanol (50 mM) in the absence or presence of EGCG (5 µM or 25 µM). Results The EGCG pre‐treatment abolished ethanol‐induced lipid peroxidation of the cell membrane, loss of total superoxide dismutase (SOD) activity and suppressed ethanol‐induced gene expressions of Mn‐ and Cu/Zn‐SOD. EGCG also suppressed ethanol‐induced p38 mitogen‐activated protein (MAP) kinase phosphorylation, α‐smooth muscle actin production in PSCs and activated transforming growth factor‐β1 secretion into the medium. Furthermore, EGCG inhibited ethanol‐induced type‐I procollagen production and collagen secretion. In addition, EGCG inhibited transformation of freshly isolated cells to activated myofibroblast‐like phenotype. Conclusions Our results suggest that green tea and polyphenols could prevent pancreatic fibrosis by inhibiting PSC activation through the antioxidative effect.