Hydroxysafflor yellow A protects against chronic carbon tetrachloride-induced liver fibrosis

Eur J Pharmacol. 2011 Jun 25;660(2-3):438-44. doi: 10.1016/j.ejphar.2011.04.015. Epub 2011 Apr 27.


Hydroxysafflor yellow A (HSYA) was isolated from the dried flower of Carthamus tinctorius L. which was extensively used in traditional Chinese medicine to treat cirrhosis. However, the potential protective effect of HSYA in liver fibrosis is still unknown. In the present study, we investigated the effects of HSYA in rats with carbon tetrachloride (CCl4)-induced liver fibrosis. Sprague-Dawley (SD) rats were subjected to biweekly CCl4 injections over 12 weeks, while controls were given isovolumetric injections of olive oil. HSYA was given in a daily dose of 5 mg/kg by means of intraperitoneal concurrent with CCl4. Hepatic fibrosis was quantified by digital analysis of Masson's trichrome stained slides and hydroxyproline content. mRNA expression was quantified by real-time polymerase chain reaction (PCR), and protein was quantified by western blot or enzyme-linked immunosorbent assay (ELISA). CCl4 treatment induced micronodular liver fibrosis with a pronounced deposition of collagen fibers. HSYA significantly reduced liver fibrosis. HSYA down regulates α-smooth muscle actin (SMA), collagen α type I, matrix metalloproteinases (MMP)-9, and tissue inhibitors of metalloproteinases (TIMP)-1 gene expression. This was accompanied by a decreased expression of transforming growth factor (TGF)-β1 and phosphorylation of Smad4. These results indicate that HSYA might be a promising antifibrotic agent in chronic liver disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbon Tetrachloride / adverse effects*
  • Chalcone / analogs & derivatives*
  • Chalcone / pharmacology
  • Chronic Disease / prevention & control
  • Collagen Type I / genetics
  • Gene Expression Regulation, Enzymologic / drug effects
  • Hepatic Stellate Cells / drug effects
  • Hepatic Stellate Cells / metabolism
  • Hepatic Stellate Cells / pathology
  • Liver Cirrhosis / chemically induced*
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / pathology
  • Liver Cirrhosis / prevention & control*
  • Male
  • Matrix Metalloproteinase 9 / genetics
  • Phosphorylation / drug effects
  • Quinones / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Smad4 Protein / metabolism
  • Tissue Inhibitor of Metalloproteinase-1 / genetics
  • Transforming Growth Factor beta1 / metabolism


  • Collagen Type I
  • Quinones
  • Smad4 Protein
  • Tissue Inhibitor of Metalloproteinase-1
  • Transforming Growth Factor beta1
  • hydroxysafflor yellow A
  • Chalcone
  • Carbon Tetrachloride
  • Matrix Metalloproteinase 9