A Chinese herbal medicine, Gexia-Zhuyu Tang (GZT), prevents dimethylnitrosamine-induced liver fibrosis through inhibition of hepatic stellate cells proliferation

J Ethnopharmacol. 2012 Aug 1;142(3):811-8. doi: 10.1016/j.jep.2012.06.005. Epub 2012 Jun 15.

Abstract

Ethnopharmacological evidence: Gexia-Zhuyu Tang (GZT), also called Gexiazhuyu decoction (GXZYD), is a traditional Chinese herbal medicine for chronic liver diseases such as cirrhosis and liver fibrosis.

Aim of the study: In this study, we have investigated the affects of GZT on a rat model of dimethylnitrosamine (DMN)-induced liver fibrosis.

Materials and methods: In this study, the protective effects of GZT on DMN-induced liver fibrosis were measured using a rat model. Following 5 weeks of DMN-treatment (8 mg/kg, i.p., given 3 consecutive days each week), oral administration of GZT at 1.8 g/kg daily via oral gavage for 2weeks beginning at week 13.

Results: Both body and liver weights were significantly decreased. The reductions in body and liver weights corresponded with increasing liver damage severity. Furthermore, GZT-treatment remarkably decreased the levels of serum GOT (glutamate oxaloacetate transaminase) and GPT (glutamic pyruvic transaminase), and the mRNA expression levels of collagen alpha-1(I) and alpha-smooth muscle actin (alpha-SMA) in DMN-induced hepatic fibrosis. In addition, hepatic stellate cells (HSCs) play a major role in various types of liver fibrosis through initial myofibroblast transformation. The proliferation of HSCs was inhibited by GZT. Treatment with GZT also induced HSC apoptosis in a dose- and time-dependent manner. GZT treatment induced HSC apoptosis by facilitating Ca(2+) release from the mitochondria within 6h. Subsequently, caspases 3 and 12 were elevated by 72 h after treatment.

Conclusions: Our studies indicate that GZT exhibited both hepatoprotective and antifibrogenic effects in DMN-induced hepatic injury. These findings suggest that GZT may be useful in preventing the development of hepatic fibrosis.

MeSH terms

  • Actins / genetics
  • Animals
  • Apoptosis / drug effects
  • Calcium / metabolism
  • Caspase 12 / metabolism
  • Caspase 3 / metabolism
  • Cell Line
  • Cell Proliferation / drug effects
  • Collagen Type I / genetics
  • Collagen Type I, alpha 1 Chain
  • Dimethylnitrosamine
  • Drugs, Chinese Herbal / pharmacology
  • Drugs, Chinese Herbal / therapeutic use*
  • Hepatic Stellate Cells / cytology
  • Hepatic Stellate Cells / drug effects*
  • Humans
  • Liver Cirrhosis / chemically induced
  • Liver Cirrhosis / diagnostic imaging
  • Liver Cirrhosis / prevention & control*
  • Male
  • Phytotherapy*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Ultrasonography

Substances

  • Actins
  • Collagen Type I
  • Collagen Type I, alpha 1 Chain
  • Drugs, Chinese Herbal
  • RNA, Messenger
  • smooth muscle actin, rat
  • Caspase 12
  • Caspase 3
  • Dimethylnitrosamine
  • Calcium