Antifibrotic effects of chronic baicalein administration in a CCl4 liver fibrosis model in rats.
Baicalein was a major bioactive flavonoid derived from Radix Scutellariae in Xiao-Chai-Hu-Tang which was commonly used to treat chronic hepatitis and liver fibrosis in China. The aim of this study was to assess whether chronic baicalein administration could prevent liver fibrosis induced by carbon tetrachloride (CCl(4)) in rats and investigate its possible protective mechanism. The antifibrotic effects of baicalein were assessed directly by hepatic histology and indirectly by measuring levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), hepatic hyaluronic acid, laminin and procollagen type III (PCIII) in serum, as well as hydroxyproline and matrix metalloproteinases (MMPs) in liver. In addition, we further investigated protein synthesis of platelet derived growth factor (PDGF) beta receptor which has been identified as attractive target for therapeutic intervention. CCl(4) treatment increased levels of AST, ALT, hyaluronic acid, laminin, and PCIII in serum, as well as hydroxyproline and MMPs in liver. Baicalein treatment (20, 40, or 80 mg/kg for 10 weeks) dose-dependently decreased levels of these markers. Baicalein also reduced inflammation, destruction of liver architecture, and collagen accumulation and significantly inhibited protein synthesis of PDGF-beta receptor. Together, our results suggest that chronic baicalein administration inhibits stellate cell activation and proliferation by the down-regulation of PDGF-beta receptor and prevents the development of CCl(4) induced liver fibrosis in rats.
Sun
Hong
H
State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, P. R. China.
Che
Qing-Ming
QM
Zhao
Xin
X
Pu
Xiao-Ping
XP
D000818:Animals; D015415:Biomarkers / Q000097:blood; D002251:Carbon Tetrachloride / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015536:Down-Regulation / Q000187:drug effects; D024022:Fibrillar Collagens / Q000097:blood / Q000378:metabolism; D044950:Flavanones / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006820:Hyaluronic Acid / Q000097:blood; D006909:Hydroxyproline / Q000378:metabolism; D007797:Laminin / Q000097:blood; D008099:Liver / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008111:Liver Function Tests; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D020011:Protective Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D013997:Time Factors
D015415:Biomarkers; D024022:Fibrillar Collagens; D044950:Flavanones; D007797:Laminin; D020011:Protective Agents; C006680:baicalein; D006820:Hyaluronic Acid; D002251:Carbon Tetrachloride; D020797:Receptor, Platelet-Derived Growth Factor beta; D020782:Matrix Metalloproteinases; D006909:Hydroxyproline