Protective effects of extracts from Pomegranate peels and seeds on liver fibrosis induced by carbon tetrachloride in rats.
BACKGROUND
Liver fibrosis is a feature in the majority of chronic liver diseases and oxidative stress is considered to be its main pathogenic mechanism. Antioxidants including vitamin E, are effective in preventing liver fibrogenesis. Several plant-drived antioxidants, such as silymarin, baicalin, beicalein, quercetin, apigenin, were shown to interfere with liver fibrogenesis. The antioxidans above are polyphenols, flavonoids or structurally related compounds which are the main chemical components of Pomegranate peels and seeds, and the antioxidant activity of Pomegranate peels and seeds have been verified. Here we investigated whether the extracts of pomegranate peels (EPP) and seeds (EPS) have preventive efficacy on liver fibrosis induced by carbon tetrachloride (CCl4) in rats and explored its possible mechanisms.


METHODS
The animal model was established by injection with 50 % CCl4 subcutaneously in male wistar rats twice a week for four weeks. Meanwhile, EPP and EPS were administered orally every day for 4 weeks, respectively. The protective effects of EPP and EPS on biochemical metabolic parameters, liver function, oxidative markers, activities of antioxidant enzymes and liver fibrosis were determined in CCl4-induced liver toxicity in rats.


RESULTS
Compared with the sham group, the liver function was worse in CCl4 group, manifested as increased levels of serum alanine aminotransferase, aspartate aminotransferase and total bilirubin. EPP and EPS treatment significantly ameliorated these effects of CCl4. EPP and EPS attenuated CCl4-induced increase in the levels of TGF-β1, hydroxyproline, hyaluronic acid laminin and procollagen type III. They also restored the decreased superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities and inhibited the formation of lipid peroxidized products in rats treated with CCl4.


CONCLUSIONS
The EPP and EPS have protective effects against liver fibrosis induced by CCl4, and its mechanisms might be associated with their antioxidant activity, the ability of decreasing the level of TGF-β1 and inhibition of collagen synthesis.
Department of Pharmacology, Xi'an Jiaotong University Health Science Center, P.O. Box 77#, No.76 Yanta West Road, Xi'an, 710061, People's Republic of China.|Department of Pharmacy, Xi'an Chest Hospital, Xi'an, 710061, People's Republic of China.
Xiang-Lan
XL
Wei
Department of Gastroenterology, The 451 Hospital of the Chinese People's Liberation Army, Xi'an, 710054, People's Republic of China.
Ru-Tang
RT
Fang
Department of pediatrics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, People's Republic of China.
Yong-Hua
YH
Yang
Department of Pharmacology, Xi'an Jiaotong University Health Science Center, P.O. Box 77#, No.76 Yanta West Road, Xi'an, 710061, People's Republic of China.
Xue-Yuan
XY
Bi
Department of Pharmacy, Xi'an Chest Hospital, Xi'an, 710061, People's Republic of China.
Guo-Xia
GX
Ren
Department of Pharmacy, Xi'an Chest Hospital, Xi'an, 710061, People's Republic of China.
A-Li
AL
Luo
Department of Pharmacology, Xi'an Jiaotong University Health Science Center, P.O. Box 77#, No.76 Yanta West Road, Xi'an, 710061, People's Republic of China. zhaomingxjtu@163.com.
Ming
M
Zhao
Department of Pharmacology, Xi'an Jiaotong University Health Science Center, P.O. Box 77#, No.76 Yanta West Road, Xi'an, 710061, People's Republic of China. zwj@mail.xjtu.edu.cn.
Wei-Jin
WJ
Zang
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002251:Carbon Tetrachloride; D004195:Disease Models, Animal; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008111:Liver Function Tests; D029561:Lythraceae / Q000737:chemistry*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012639:Seeds / Q000737:chemistry; D013154:Spleen / Q000378:metabolism
D015415:Biomarkers; D010936:Plant Extracts; D002251:Carbon Tetrachloride