Protective effects of green tea polyphenol extracts against ethanol-induced gastric mucosal damages in rats: stress-responsive transcription factors and MAP kinases as potential targets.
There are multiple lines of compelling evidence from epidemiologic and laboratory studies supporting that frequent consumption of green tea is inversely associated with the risk of chronic human diseases including cancer. The chemopreventive and chemoprotective effects of green tea have been largely attributed to antioxidative and anti-inflammatory activities of its polyphenolic constituents, such as epigallocatechin gallate. The present study was designed to evaluate the efficacy of green tea polyphenols in protecting against alcohol-induced gastric damage and to elucidate the underlying mechanisms. Intragastric administration of ethanol to male Sprague-Dawley rats caused significant gastric mucosal damage, which was accompanied by elevated expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) as well as transient activation of redox-sensitive transcription factors, such as NF-kappaB and AP-1, and mitogen-activated protein kinases (MAPKs). Oral administration of the green tea polyphenolic extract (GTE) significantly ameliorated mucosal damages induced by ethanol and also attenuated the ethanol-induced expression of COX-2 and iNOS. Inactivation of MAPKs, especially p38 and ERKl/2, by GTE might be responsible for inhibition of ethanol-induced expression of COX-2 and iNOS.
Lee
Jeong-Sang
JS
College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
Oh
Tae-Young
TY
Kim
Young-Kyung
YK
Baik
Joo-Hyun
JH
So
Sung
S
Hahm
Ki-Baik
KB
Surh
Young-Joon
YJ
D000818:Animals; D051545:Cyclooxygenase 1 / Q000187:drug effects / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000009:adverse effects*; D005419:Flavonoids / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005756:Gastritis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D018840:HSP70 Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects*; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D059808:Polyphenols; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological; D013662:Tea; D018808:Transcription Factor AP-1 / Q000187:drug effects / Q000378:metabolism; D014157:Transcription Factors / Q000187:drug effects*
D005419:Flavonoids; D018840:HSP70 Heat-Shock Proteins; D008565:Membrane Proteins; D016328:NF-kappa B; D010636:Phenols; D010936:Plant Extracts; D059808:Polyphenols; D013662:Tea; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D000431:Ethanol; D052247:Nitric Oxide Synthase Type II; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496513:Ptgs1 protein, rat; D020928:Mitogen-Activated Protein Kinases