Garlic extract attenuating rat liver fibrosis by inhibiting TGF-β1

• Published in: Clinical nutrition (Edinburgh, Scotland) Vol. 32; no. 2; pp. 252 - 258
• Main Authors: D’Argenio, Giuseppe, Mazzone, Giovanna, Ribecco, Maria T., Lembo, Vincenzo, Vitaglione, Paola, Guarino, Maria, Morisco, Filomena, Napolitano, Manuela, Fogliano, Vincenzo, Caporaso, Nicola
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.04.2013; Elsevier
• Subjects: Actins; Actins - metabolism; administration & dosage; alanine transaminase; Alanine Transaminase - metabolism; Animals; antagonists & inhibitors; Antigens, CD; Antigens, CD - metabolism; Biological and medical sciences; carbon tetrachloride; Carbon Tetrachloride - administration & dosage; chemistry; collagen; drug effects; drug therapy; extracellular matrix; Feeding. Feeding behavior; Fibrosis; Fundamental and applied biological sciences. Psychology; Garlic; Garlic - chemistry; Gastroenterology and Hepatology; Gastroenterology. Liver. Pancreas. Abdomen; genes; histology; Liver; Liver - drug effects; Liver - metabolism; Liver - pathology; liver cirrhosis; Liver Cirrhosis - drug therapy; Liver Cirrhosis - pathology; liver function; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; metabolism; Other diseases. Semiology; pathology; pharmacology; Plant Extracts; Plant Extracts - pharmacology; protein synthesis; protein-glutamine gamma-glutamyltransferase; Rats; Rats, Wistar; Semaphorins; Semaphorins - metabolism; TGF-β1; therapeutics; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-1 - metabolism; transforming growth factor beta 1; Transforming Growth Factor beta1; Transforming Growth Factor beta1 - antagonists & inhibitors; Transforming Growth Factor beta1 - metabolism; Transglutaminase; Transglutaminases; Transglutaminases - antagonists & inhibitors; Transglutaminases - metabolism; Vertebrates: anatomy and physiology, studies on body, several organs or systems; TGF-β1; Garlic; Transglutaminase; Liver; Fibrosis; Hepatic fibrosis; Vertebrata; Mammalia; Rat; Animal; Rodentia; Digestive diseases; Hepatic disease; Metabolic diseases; Extract; Transforming growth factor β1
• ISSN: 0261-5614; 1532-1983; 1532-1983
• DOI: 10.1016/j.clnu.2012.07.001

We previously demonstrated the efficacy of garlic extract (GE) in the prevention of rat liver fibrosis by inhibiting tissue transglutaminase (tTG) activity. In the present study we aimed to evaluate the potential of GE in the regression of liver fibrosis and the underlining mechanism. Male Wistar rats were i.p. injected, twice a week, for 7 weeks, with CCl4 to develop liver fibrosis. Successively, a group was immediately sacrificed, while the remaining two groups received the GE or the vehicle, respectively, over the following 2 wks. A group of normal rats was also included in the study. Liver function, histology, and collagen deposition in parallel with gene and protein expression of α-SMA, tTG, TGF-β1, SEMA-7A, and metalloproteinase inhibitor 1 (TIMP1) as well as measure of active by total TGF-β1 were assessed. CCl4 administration increased alanine-aminotransferase (ALT) activity, hepatic collagen deposition and gene and protein expression of all monitored markers. GE, but not the sole vehicle, restored liver histology and function by decreasing fibrogenesis markers (α-SMA, tTG, TGF-β1, SEMA-7A and TIMP1). Active by total TGF-β1 was significantly reduced (p < 0.05) in GE treated rats compared to the CCl4 at 7 weeks, and vehicle rats. These findings concurrently suggested that GE elicited therapeutic effect against liver fibrosis. Regression of liver fibrosis occurred by reducing myofibroblasts (through modulation of HSCs activation mechanisms), remodelling extracellular matrix (through increase of its degradation) and regenerating liver tissue and functions: three processes regulated by fine mechanisms where active TGF-β1 and tTG play a central role.