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Green tea polyphenol (-)-epigallocatechin-3-gallate inhibits ethanol-induced activation of pancreatic stellate cells.
Eur J Clin Invest. 2006 Feb; 36(2):113-22.EJ

Abstract

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 microM or 25 microM).

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, alpha-smooth muscle actin production in PSCs and activated transforming growth factor-beta1 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.

Authors+Show Affiliations

Third Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16436093

Citation

Asaumi, H, et al. "Green Tea Polyphenol (-)-epigallocatechin-3-gallate Inhibits Ethanol-induced Activation of Pancreatic Stellate Cells." European Journal of Clinical Investigation, vol. 36, no. 2, 2006, pp. 113-22.
Asaumi H, Watanabe S, Taguchi M, et al. Green tea polyphenol (-)-epigallocatechin-3-gallate inhibits ethanol-induced activation of pancreatic stellate cells. Eur J Clin Invest. 2006;36(2):113-22.
Asaumi, H., Watanabe, S., Taguchi, M., Tashiro, M., Nagashio, Y., Nomiyama, Y., Nakamura, H., & Otsuki, M. (2006). Green tea polyphenol (-)-epigallocatechin-3-gallate inhibits ethanol-induced activation of pancreatic stellate cells. European Journal of Clinical Investigation, 36(2), 113-22.
Asaumi H, et al. Green Tea Polyphenol (-)-epigallocatechin-3-gallate Inhibits Ethanol-induced Activation of Pancreatic Stellate Cells. Eur J Clin Invest. 2006;36(2):113-22. PubMed PMID: 16436093.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Green tea polyphenol (-)-epigallocatechin-3-gallate inhibits ethanol-induced activation of pancreatic stellate cells. AU - Asaumi,H, AU - Watanabe,S, AU - Taguchi,M, AU - Tashiro,M, AU - Nagashio,Y, AU - Nomiyama,Y, AU - Nakamura,H, AU - Otsuki,M, PY - 2006/1/27/pubmed PY - 2006/8/15/medline PY - 2006/1/27/entrez SP - 113 EP - 22 JF - European journal of clinical investigation JO - Eur J Clin Invest VL - 36 IS - 2 N2 - 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 microM or 25 microM). 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, alpha-smooth muscle actin production in PSCs and activated transforming growth factor-beta1 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. SN - 0014-2972 UR - https://www.unboundmedicine.com/medline/citation/16436093/Green_tea_polyphenol_____epigallocatechin_3_gallate_inhibits_ethanol_induced_activation_of_pancreatic_stellate_cells_ L2 - https://doi.org/10.1111/j.1365-2362.2006.01599.x DB - PRIME DP - Unbound Medicine ER -