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

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.
AuthorsTzung-Yan Lee, Hen-Hong Chang, Mei-Yao Wu, Han-Chieh Lin
JournalThe Journal of pharmacy and pharmacology (J Pharm Pharmacol) Vol. 59 Issue 4 Pg. 583-90 (Apr 2007) ISSN: 0022-3573 [Print] England
PMID17430643 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Drugs, Chinese Herbal
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • bcl-2-Associated X Protein
  • Cytochromes c
  • Caspase 3
  • Caspase 8
  • Glutathione
Topics
  • Animals
  • Apoptosis (drug effects)
  • Artemisia (chemistry)
  • Bile Ducts (surgery)
  • Caspase 3 (drug effects, metabolism)
  • Caspase 8 (drug effects, metabolism)
  • Cholestasis, Extrahepatic (drug therapy, physiopathology)
  • Cytochromes c (chemistry, drug effects)
  • Disease Models, Animal
  • Drugs, Chinese Herbal (administration & dosage, chemistry, pharmacology)
  • Gardenia (chemistry)
  • Gene Expression (drug effects)
  • Glutathione (chemistry, drug effects)
  • Hepatocytes (drug effects, pathology)
  • Hypertension, Portal (drug therapy)
  • Ligation
  • Liver (drug effects, metabolism, pathology)
  • Male
  • Medicine, Chinese Traditional
  • Phytotherapy
  • RNA, Messenger (drug effects, metabolism)
  • Rats
  • Rats, Sprague-Dawley
  • Rheum (chemistry)
  • Tumor Necrosis Factor-alpha (blood, drug effects)
  • bcl-2-Associated X Protein (chemistry, drug effects)

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