title: Boswellia serrata and Salvia miltiorrhiza extracts reduce DMN-induced hepatic fibrosis in mice by TGF-beta1 downregulation.
abstract: BACKGROUND
  Hepatic fibrosis is characterised by a progressive accumulation of fibrillar extracellular matrix (ECM) proteins, including collagen that occurs in chronic liver diseases. Transforming growth factor-beta1 (TGF-beta)/Smad3 signalling plays a major role in tissue fibrogenesis acting as a potent stimulus of ECM accumulation.
  
  
  OBJECTIVE
  To evaluate the effects of a combined therapy with anti-inflammatory Boswellia and anti-fibrotic Salvia extracts on the course of chronic hepatitis-associated fibrosis induced by dimethylnitrosamine (DMN) in mice, as well as on the hepatic expression of TGF-beta1 and Smad proteins.
  
  
  METHODS
  Chronic hepatitis-associated fibrosis was induced in mice by intraperitoneal DMN administration. Mice were assigned to 5 groups: controls; DMN without any treatment; DMN treated orally with Boswellia extracts (50 mg/kg/day); DMN treated orally with Salvia extracts (150 mg/ kg/day); DMN treated orally with both Boswellia (50 mg/kg/day) and Salvia extracts (150 mg/kg/ day). The liver was excised for macroscopic examination and histological, morphometric and immunohistochemical (IHC) analyses. For IHC, alpha-smooth muscle actin (alpha-SMA), collagen types I-III, TGF-beta1, connective tissue growth factor (CTGF), Smad3, Smad7, CD3, PCNA and TUNEL antibodies were used.
  
  
  RESULTS
  The combined oral administration of Boswellia and Salvia extracts improved the course and macroscopic findings of DMN-induced chronic hepatitis-associated fibrosis. The histological severity of the hepatic fibrosis showed a marked improvement following treatment and was associated with a reduction in the hepatic expression of alpha-SMA, collagen I-III, CTGF, TGF-beta1, Smad3, and Smad7.
  
  
  CONCLUSIONS
  These data demonstrate that co-treatment of Boswellia plus Salvia extracts is effective in preventing hepatic fibrosis in DMN-induced chronic hepatitis. The anti-fibrotic properties are mainly related to Salvia extracts and appear to be mediated by the inhibition of the TGF-beta1/Smad3 pathway.
authors.affiliation: Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Sferra
authors.forename: A
authors.initials: A
authors.lastname: Vetuschi
authors.forename: V
authors.initials: V
authors.lastname: Catitti
authors.forename: S
authors.initials: S
authors.lastname: Ammanniti
authors.forename: S
authors.initials: S
authors.lastname: Pompili
authors.forename: D
authors.initials: D
authors.lastname: Melideo
authors.forename: G
authors.initials: G
authors.lastname: Frieri
authors.forename: E
authors.initials: E
authors.lastname: Gaudio
authors.forename: G
authors.initials: G
authors.lastname: Latella
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D029743:Boswellia; D001892:Camphanes; D003094:Collagen / Q000378:metabolism; D004128:Dimethylnitrosamine; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005260:Female; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D053723:Panax notoginseng; D010936:Plant Extracts / Q000627:therapeutic use*; D027561:Salvia miltiorrhiza; D051900:Smad3 Protein / Q000378:metabolism; D051906:Smad7 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D001892:Camphanes; D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D051906:Smad7 Protein; C497807:Smad7 protein, mouse; D053773:Transforming Growth Factor beta1; C000604051:danshen dripping pill; D003094:Collagen; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D004128:Dimethylnitrosamine