title: Garlic extract attenuating rat liver fibrosis by inhibiting TGF-β1.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Male Wistar rats were i.p. injected, twice a week, for 7 weeks, with CCl(4) 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.
  
  
  RESULTS
  CCl(4) 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 CCl(4) at 7 weeks, and vehicle rats.
  
  
  CONCLUSIONS
  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.
authors: Gastroenterology Unit, Department of Clinical and Experimental Medicine, Federico II University of Naples, Italy. dargenio@unina.it
authors: Giuseppe
authors: G
authors: D'Argenio
authors: Giovanna
authors: G
authors: Mazzone
authors: Maria T
authors: MT
authors: Ribecco
authors: Vincenzo
authors: V
authors: Lembo
authors: Paola
authors: P
authors: Vitaglione
authors: Maria
authors: M
authors: Guarino
authors: Filomena
authors: F
authors: Morisco
authors: Manuela
authors: M
authors: Napolitano
authors: Vincenzo
authors: V
authors: Fogliano
authors: Nicola
authors: N
authors: Caporaso
mesh_terms: D000199:Actins / Q000378:metabolism; D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002251:Carbon Tetrachloride / Q000008:administration & dosage; D005737:Garlic / Q000737:chemistry*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D039961:Semaphorins / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011503:Transglutaminases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000199:Actins; D000410:Alanine Transaminase; D015703:Antigens, CD; D002251:Carbon Tetrachloride; D010936:Plant Extracts; D039961:Semaphorins; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; D011503:Transglutaminases; C558466:Sema7a protein, rat; C576839:TIMP1 protein, rat; C498862:Acta2 protein, rat