Salvianolic acid A attenuates CCl4-induced liver fibrosis by regulating the PI3K/AKT/mTOR, Bcl-2/Bax and caspase-3/cleaved caspase-3 signaling pathways

Drug Des Devel Ther. 2019 May 31:13:1889-1900. doi: 10.2147/DDDT.S194787. eCollection 2019.


Background: Liver fibrosis occurs due to chronic liver disease due to multiple pathophysiological causes. The main causes for this condition are chronic alcohol abuse, nonalcoholic steatohepatitis, and infection due to hepatitis C virus. Currently, there is more and more information available about the molecular as well as cellular mechanisms, which play a role in the advancement of liver fibrosis. However, there is still no effective therapy against it. Purpose: In order to find an effective treatment against liver fibrosis, our study explored whether salvianolic acid A (SA-A), a traditional Chinese medicine extracted from the plant Danshen, could effectively inhibit the liver fibrosis, which is induced by CCl4 in vivo. Methods: The effects of SA-A were evaluated by assessing the parameters related to liver fibrosis such as body weight, histological changes, and biochemical parameters. Thereafter, the related protein or gene levels of P13K/AKT/mTOR, Bcl-2/Bax and caspase-3/cleaved caspase-3 signaling pathways were determined by western blotting, real-time PCR or immunohistochemistry staining. Results: According to the results of our study, SA-A could reduce liver fibrosis by inhibiting liver function, liver fibrosis index, collagen deposition, and improving the degree of liver fibrosis in rats. Mechanistically, the PI3K/AKT/mTOR signaling cascade was inhibited by SA-A to prevent the stimulation of hepatic stellate cell, as well as the synthesis of extracellular matrix, and regulated Bcl-2/Bax and caspase-3/cleaved caspase-3 signaling pathways to prevent hepatocyte apoptosis. Conclusion: The novel findings of this study suggested that SA-A could reduce liver fibrosis and the molecular mechanisms behind it are closely associated with the regulation of PI3K/AKT/mTOR, Bcl-2/Bax and caspase-3/cleaved caspase-3 signaling pathways.

Keywords: AKT/mTOR; Bcl-2/Bax; caspase-3/cleaved caspase-3; liver fibrosis; salvianolic acid A.

MeSH terms

  • Animals
  • Caffeic Acids / pharmacology*
  • Carbon Tetrachloride
  • Caspase 3 / metabolism
  • Enzyme Inhibitors / pharmacology*
  • Lactates / pharmacology*
  • Liver Cirrhosis / chemically induced
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / metabolism
  • Male
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / metabolism*
  • bcl-2-Associated X Protein / metabolism*


  • Bax protein, rat
  • Caffeic Acids
  • Enzyme Inhibitors
  • Lactates
  • bcl-2-Associated X Protein
  • salvianolic acid A
  • Carbon Tetrachloride
  • mTOR protein, rat
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Casp3 protein, rat
  • Caspase 3