Green tea polyphenol decreases the severity of portosystemic collaterals and mesenteric angiogenesis in rats with liver cirrhosis.
Abnormal angiogenesis in liver cirrhosis often leads to severe complications such as variceal haemorrhage and encephalopathy. Furthermore, splanchnic angiogenesis elevates portal pressure, in which angiogenic factors play pivotal roles. GTP (green tea polyphenol) extracted from Camellia sinensis has anti-angiogenic properties, but the effects on the parameters described above in cirrhosis have not been investigated. The aim of the present study was to determine the effects of GTP in cirrhosis and to investigate the underlying mechanism. Liver cirrhosis was induced in Spraque-Dawley rats by common BDL (bile duct ligation). They randomly received GTP or DW (distilled water, vehicle) for 28 days, then haemodynamic parameters, portosystemic shunting, mesenteric window vascular density, intrahepatic angiogenesis, liver fibrosis, plasma VEGF (vascular endothelial growth factor) concentration, mesenteric angiogenic factor and receptor protein expression, and serum and mesenteric oxidative stress parameters were assessed. Compared with the DW group, GTP significantly decreased portosystemic shunting, liver fibrosis, intrahepatic angiogenesis, mesenteric window vascular density, VEGF concentration and down-regulated the mesenteric HIF (hypoxia-inducible factor)-1α, VEGF and phospho-Akt expression. In conclusion, GTP ameliorates the severity of portosystemic shunting and mesenteric angiogenesis via the suppression of HIF-1α, Akt activation and VEGF. GTP appears to be an appropriate agent in controlling portal hypertension-related complications via anti-angiogenesis.
Shao-Jung
SJ
Hsu
Sun-Sang
SS
Wang
I-Fang
IF
Hsin
Fa-Yauh
FY
Lee
Hui-Chun
HC
Huang
Teh-Ia
TI
Huo
Wen-Shin
WS
Lee
Han-Chieh
HC
Lin
Shou-Dong
SD
Lee
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D028241:Camellia sinensis; D003097:Collateral Circulation / Q000187:drug effects*; D006975:Hypertension, Portal / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008102:Liver Circulation / Q000187:drug effects*; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000503:physiopathology; D009389:Neovascularization, Pathologic; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal; D059808:Polyphenols / Q000494:pharmacology*; D017082:Portal Pressure / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D020533:Angiogenesis Inhibitors; D015415:Biomarkers; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010936:Plant Extracts; D059808:Polyphenols; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D051057:Proto-Oncogene Proteins c-akt