Weerawatanakorn, M.M.WeerawatanakornLee, Y.-L.Y.-L.LeeTsai, C.-Y.C.-Y.TsaiLai, C.-S.C.-S.LaiWan, X.X.WanHo, C.-T.C.-T.HoLi, S.S.LiMIN-HSIUNG PAN2018-09-102018-09-102015http://www.scopus.com/inward/record.url?eid=2-s2.0-84931096811&partnerID=MN8TOARShttp://scholars.lib.ntu.edu.tw/handle/123456789/391079Liver cirrhosis is responsible for hepatic fibrosis resulting in high mortality and is also a risk factor for developing hepatocellular carcinoma (HCC), which is the fifth most common cancer in men and the seventh in women globally. Several studies have found effective anti-cancer activities of theaflavins, the major black tea polyphenols. The objective of this study was to investigate the protective effects of theaflavin-enriched black tea extracts (TF-BTE) on hepatic fibrosis induced by dimethylnitrosamine (DMN) administration in Sprague-Dawley (SD) rats. Treatment of SD rats with DMN (10 mg per kg bw) for 4 weeks produced inflammation and remarkable liver fibrosis assessed by serum biochemistry and histopathological examination. Fibrotic status and the activation of hepatic stellate cells were improved by oral administration of 40% theaflavins in black tea extracts (40% TF-BTE) as evidenced by histopathological examination. Oral administration of 40% TF-BTE at a low dose of 50 mg per kg bw per day and a high dose of 100 mg per kg bw per day attenuated the DMN-induced elevation of serum GOT (glutamate oxaloacetate transaminase) and GPT (glutamic pyruvic transaminase) levels and reduced necrosis, bile duct proliferation, and inflammation. Western blot analyses revealed that TF-BTE inhibited the expression of liver alpha-smooth muscle actin (α-SMA) and transforming growth factor-β1 (TGF-β1) protein. The histochemical examination showed the inhibitory effect of TF-BTE on the p-Smad3 expression. Overall, these data demonstrated that TF-BTE exhibited hepatoprotective effects on experimental fibrosis, potentially by inhibiting the TGF-β1/Smad signaling. ? 2015 The Royal Society of Chemistry.[SDGs]SDG3Cell death; Diseases; Muscle; Nitrosamines; Pathology; Proteins; Rats; Anticancer activities; Glutamic-pyruvic transaminase; Hepatic stellate cells; Hepatocellular carcinoma; Hepatoprotective effects; Histopathological examinations; Transforming growth factors; Western-blot analysis; Tea; Camellia sinensis; Rattus; antineoplastic agent; biflavonoid; biological marker; carcinogen; catechin; dimethylnitrosamine; plant extract; protective agent; theaflavin; adverse effects; analysis; animal; antagonists and inhibitors; blood; Camellia sinensis; Carcinoma, Hepatocellular; chemically induced; chemistry; comparative study; diet supplementation; drug effects; Drug-Induced Liver Injury; food handling; immunology; intrahepatic bile duct; liver; Liver Cirrhosis, Experimental; Liver Neoplasms; male; metabolism; oxidation reduction reaction; pathology; plant leaf; randomization; Sprague Dawley rat; Animals; Anticarcinogenic Agents; Biflavonoids; Bile Ducts, Intrahepatic; Biomarkers; Camellia sinensis; Carcinogens; Carcinoma, Hepatocellular; Catechin; Dietary Supplements; Dimethylnitrosamine; Drug-Induced Liver Injury; Food Handling; Liver; Liver Cirrhosis, Experimental; Liver Neoplasms; Male; Oxidation-Reduction; Plant Extracts; Plant Leaves; Protective Agents; Random Allocation; Rats, Sprague-Dawleyjournal article10.1039/c5fo00126a