Polyphenols from Camellia sinenesis attenuate experimental cholestasis-induced liver fibrosis in rats.
Accumulation of hydrophobic bile acids during cholestasis leads to generation of oxygen free radicals in the liver. Accordingly, this study investigated whether polyphenols from green tea Camellia sinenesis, which are potent free radical scavengers, decrease hepatic injury caused by experimental cholestasis. Rats were fed a standard chow or a diet containing 0.1% polyphenolic extracts from C. sinenesis starting 3 days before bile duct ligation. After bile duct ligation, serum alanine transaminase increased to 760 U/l after 1 day in rats fed a control diet. Focal necrosis and bile duct proliferation were also observed after 1-2 days, and fibrosis developed 2-3 wk after bile duct ligation. Additionally, procollagen-alpha1(I) mRNA increased 30-fold 3 wk after bile duct ligation, accompanied by increased expression of alpha-smooth muscle actin and transforming growth factor-beta and the accumulation of 4-hydroxynenonal, an end product of lipid peroxidation. Polyphenol feeding blocked or blunted all of these bile duct ligation-dependent changes by 45-73%. Together, the results indicate that cholestasis due to bile duct ligation causes liver injury by mechanisms involving oxidative stress. Polyphenols from C. sinenesis scavenge oxygen radicals and prevent activation of stellate cells, thereby minimizing liver fibrosis.
Zhong
Zhi
Z
Dept. of Cell and Developmental Biology, CB# 7090, Univ. of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7090, USA. zzhong@med.unc.edu
Froh
Matthias
M
Lehnert
Mark
M
Schoonhoven
Robert
R
Yang
Liu
L
Lind
Henrik
H
Lemasters
John J
JJ
Thurman
Ronald G
RG
D000199:Actins / Q000037:antagonists & inhibitors; D000818:Animals; D001652:Bile Ducts; D002455:Cell Division / Q000187:drug effects; D002779:Cholestasis / Q000150:complications* / Q000503:physiopathology; D005419:Flavonoids / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007728:Kupffer Cells; D008026:Ligation; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D059808:Polyphenols; D051381:Rats; D017207:Rats, Sprague-Dawley; D013662:Tea / Q000737:chemistry*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000199:Actins; D005419:Flavonoids; D016166:Free Radical Scavengers; D016328:NF-kappa B; D010636:Phenols; D010936:Plant Extracts; D059808:Polyphenols; D013662:Tea; D018808:Transcription Factor AP-1; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha