Yin-Chen-Hao-Tang ameliorates obstruction-induced hepatic apoptosis in rats

J Pharm Pharmacol. 2007 Apr;59(4):583-90. doi: 10.1211/jpp.59.4.0014.

Abstract

The accumulation of hydrophobic bile acids in the liver is considered to play a pivotal role in the induction of apoptosis of hepatocytes during cholestasis. Thus, factors that affect apoptosis may be used to modulate liver fibrosis. Yin-Chen-Hao-Tang (YCHT) decoctions have been recognised as a hepatoprotective agent for jaundice and various types of liver diseases. We used an experimental rat model of bile-duct ligation (BDL) to test whether YCHT plays a regulatory role in the pathogenesis of hepatic apoptosis. BDL-plus-YCHT groups received 250 or 500 mg kg (-1) YCHT by gavage once daily for 27 days. YCHT significantly ameliorated the portal hypertensive state and serum TNF-alpha compared with the vehicle-treated control group. In BDL-plus-YCHT-treated rats, hepatic glutathione contents were significantly higher than than in BDL-only rats. BDL caused a prominent liver apoptosis that was supported by an increase in Bax and cytochrome c protein and increased expression of Bax and Bcl-2 messenger RNA. The normalising effect of YCHT on expression of Bax and Bcl-2 mRNA was dependent on the dose of YCHT, 500 mg kg (-1) having the greater effect on both Bax and Bcl-2 of mRNA levels. Additionally, YCHT treatment down-regulated both hepatic caspase-3 and -8 activities of BDL rats. This study demonstrates the anti-apoptotic properties of YCHT and suggests a potential application of YCHT in the clinical management of hepatic disease resulting from biliary obstruction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Artemisia / chemistry
  • Bile Ducts / surgery
  • Caspase 3 / drug effects
  • Caspase 3 / metabolism
  • Caspase 8 / drug effects
  • Caspase 8 / metabolism
  • Cholestasis, Extrahepatic / drug therapy
  • Cholestasis, Extrahepatic / physiopathology
  • Cytochromes c / chemistry
  • Cytochromes c / drug effects
  • Disease Models, Animal
  • Drugs, Chinese Herbal / administration & dosage
  • Drugs, Chinese Herbal / chemistry
  • Drugs, Chinese Herbal / pharmacology*
  • Gardenia / chemistry
  • Gene Expression / drug effects
  • Glutathione / chemistry
  • Glutathione / drug effects
  • Hepatocytes / drug effects
  • Hepatocytes / pathology
  • Hypertension, Portal / drug therapy
  • Ligation
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Medicine, Chinese Traditional*
  • Phytotherapy*
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Rheum / chemistry
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / drug effects
  • bcl-2-Associated X Protein / chemistry
  • bcl-2-Associated X Protein / drug effects

Substances

  • Drugs, Chinese Herbal
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • bcl-2-Associated X Protein
  • Cytochromes c
  • Caspase 3
  • Caspase 8
  • Glutathione