Yin-Chen-Hao-Tang ameliorates obstruction-induced hepatic apoptosis in rats.
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.
Lee
Tzung-Yan
TY
Graduate Institute of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan. joyamen@mail.cgu.edu.tw
Chang
Hen-Hong
HH
Wu
Mei-Yao
MY
Lin
Han-Chieh
HC
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D019306:Artemisia / Q000737:chemistry; D001652:Bile Ducts / Q000601:surgery; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D053181:Caspase 8 / Q000187:drug effects / Q000378:metabolism; D001651:Cholestasis, Extrahepatic / Q000188:drug therapy / Q000503:physiopathology; D045304:Cytochromes c / Q000737:chemistry / Q000187:drug effects; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D032062:Gardenia / Q000737:chemistry; D015870:Gene Expression / Q000187:drug effects; D005978:Glutathione / Q000737:chemistry / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D006975:Hypertension, Portal / Q000188:drug therapy; D008026:Ligation; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008516:Medicine, Chinese Traditional; D008517:Phytotherapy; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012250:Rheum / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000737:chemistry / Q000187:drug effects
D004365:Drugs, Chinese Herbal; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D053148:Caspase 3; D053181:Caspase 8; D005978:Glutathione