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540062 
Journal Article 
Effect of berberine on hepatocyte proliferation, inducible nitric oxide synthase expression, cytochrome P450 2E1 and 1A2 activities in diethylnitrosamine- and phenobarbital-treated rats 
Zhao, X; Zhang, JJ; Wang, X; Bu, XY; Lou, YQ; Zhang, GL 
2008 
Yes 
Biomedicine & Pharmacotherapy
ISSN: 0753-3322
EISSN: 1950-6007 
62 
9 
567-572 
English 
17418998 
WOS:000261271900003 
This study investigated the effect of berberine on the early phase of hepatocarcinogenesis stimulated by diethylnitrosamine (DEN, 150 mg/kg, 4 weeks) plus phenobarbital (PB, 75 mg/kg 7 days) in rats. The expressions of proliferating cell nuclear antigen (PCNA) and inducible nitric oxide synthase (iNOS) were evaluated by immunohistochemistry. The activities of CYP isoenzymes were analyzed using different probe drugs including chlorzoxazone (CYP2E1) and phenacetin (CYP1A2) by high-performance liquid chromatography (HPLC) in vivo or in vitro. Results showed that the expressions of PCNA and iNOS were induced by DEN plus PB in liver tissues. Oral administration of berberine (50 mg/kg) inhibited the hepatocyte proliferation and iNOS expression, decreased cytochrome P450 content, inhibited activities of CYP2E1 and CYP1A2 in DEN-plus-PB-treated rats in vivo. Moreover. berberine (10, 50 and 100 mu M) inhibited the activities of CYP2E1 and CYP1A2 in microsomes isolated from DEN-plus-PB-treated rats in vitro, suggesting that anti-hepatocarcinogenetic potential of berberine might be due to inhibiting oxidative metabolic activities of CYP2E1 and CYP1A2. and decreasing NO production in rats. (C) 2007 Elsevier Masson SAS. All rights reserved. 
Berbetine; Diethylnitrosamine (DEN); Phenobarbital; Cytochrome P450 2E1; (CYP2E1); Cytochrome P450 1A2 (CYP1A2); liver-injury; n-nitrosodiethylamine; carcinogenesis; mice; constituents; inhibition; metabolism; goldenseal; microsomes; oxidation