Huangqi decoction inhibits apoptosis and fibrosis, but promotes Kupffer cell activation in dimethylnitrosamine-induced rat liver fibrosis

BMC Complement Altern Med. 2012 Apr 24:12:51. doi: 10.1186/1472-6882-12-51.

Abstract

Background: Previously, Huangqi decoction (HQD) has been found to have a potential therapeutic effect on DMN-induced liver cirrhosis. Here, the mechanisms of HQD action against liver fibrosis were investigated in relation to hepatocyte apoptosis and hepatic inflammation regulation.

Methods: Liver fibrosis was induced by DMN administration for 2 or 4 weeks. Hepatocyte apoptosis and of Kupffer cells (KC) and hepatic stellate cells (HSC) interaction were investigated using confocal microscopy. The principle cytokines, fibrogenic proteins and apoptotic factors were investigated using western blot analysis.

Results: Compared with the DMN-water group, HQD showed decreased hepatocyte apoptosis and reduced expression of apoptotic effectors, cleaved-caspase-3, and fibrotic factors, such as smooth muscle α-actin (α-SMA), transforming growth factor beta-1 (TGF-β1). However, the KC marker CD68 increased significantly in DMN-HQD liver. Confocal microscopy demonstrated widespread adhesion of KCs to HSCs in DMN-water and DMN-HQD rats liver.

Conclusions: HQD exhibited positive protective effects against liver fibrosis; its mechanism of action was associated with protection from hepatocyte apoptosis and the promotion of CD68 expression in the devolopment of liver fibrosis to cirrhosis development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Caspase 3 / genetics
  • Caspase 3 / immunology
  • Dimethylnitrosamine / adverse effects
  • Drugs, Chinese Herbal / administration & dosage*
  • Fibrosis
  • Hepatocytes
  • Humans
  • Kupffer Cells / cytology
  • Kupffer Cells / drug effects*
  • Kupffer Cells / immunology
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / immunology
  • Liver Cirrhosis / pathology
  • Liver Cirrhosis / physiopathology*
  • Male
  • Protective Agents / administration & dosage*
  • Rats
  • Rats, Wistar
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / immunology

Substances

  • Drugs, Chinese Herbal
  • Protective Agents
  • Transforming Growth Factor beta1
  • Caspase 3
  • Dimethylnitrosamine