Protective effect of theaflavin-enriched black tea extracts against dimethylnitrosamine-induced liver fibrosis in rats.
Liver 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.
Department of Agro-Industry, Faculty of Agriculture, Natural Resources and Environment, Naresuan University, Phitsanulok 65000, Thailand.
Monthana
M
Weerawatanakorn
You-Li
YL
Lee
Chen-Yu
CY
Tsai
Ching-Shu
CS
Lai
Xiaochun
X
Wan
Chi-Tang
CT
Ho
Shiming
S
Li
Min-Hsiung
MH
Pan
D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use; D044946:Biflavonoids / Q000008:administration & dosage / Q000009:adverse effects / Q000032:analysis / Q000627:therapeutic use; D001653:Bile Ducts, Intrahepatic / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D028241:Camellia sinensis / Q000737:chemistry*; D002273:Carcinogens / Q000037:antagonists & inhibitors / Q000633:toxicity; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000517:prevention & control; D002392:Catechin / Q000008:administration & dosage / Q000009:adverse effects / Q000032:analysis / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D019587:Dietary Supplements / Q000009:adverse effects / Q000032:analysis; D004128:Dimethylnitrosamine / Q000037:antagonists & inhibitors* / Q000633:toxicity; D005511:Food Handling; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008113:Liver Neoplasms / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D010084:Oxidation-Reduction; D010936:Plant Extracts / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D018515:Plant Leaves / Q000737:chemistry; D020011:Protective Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley
D016588:Anticarcinogenic Agents; D044946:Biflavonoids; D015415:Biomarkers; D002273:Carcinogens; D010936:Plant Extracts; D020011:Protective Agents; C056068:theaflavin; D002392:Catechin; D004128:Dimethylnitrosamine