Effect of berberine on hepatocyte proliferation, inducible nitric oxide synthase expression, cytochrome P450 2E1 and 1A2 activities in diethylnitrosamine- and phenobarbital-treated rats
Effect of berberine on hepatocyte proliferation, inducible nitric oxide synthase expression, cytochrome P450 2E1 and 1A2 activities in diethylnitrosamine- and phenobarbital-treated rats
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DOI：
10.1016/j.biopha.2007.02.009
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发表时间：
2008-11-01
影响因子：
7.5
通讯作者：
Zhang, Guo-Liang
中科院分区：
文献类型：
--
作者：
Zhao, Xuan;Zhang, Jun-Jie;Zhang, Guo-Liang
本文观察了小檗碱对二乙基亚硝胺（DEN，150 mg/kg，4周）加苯巴比妥（PB，75 mg/kg，7天）诱发大鼠肝癌早期的影响。免疫组化检测增殖细胞核抗原（PCNA）和诱导型一氧化氮合酶（iNOS）的表达。采用高效液相色谱法（HPLC），以氯唑沙宗（CYP 2 E1）和非那西丁（CYP 1A 2）为探针药物，在体内或体外分析了CYP 2 E1和CYP 1A 2同工酶活性。结果表明，DEN + PB可诱导肝组织中PCNA和iNOS的表达。小檗碱（50 mg/kg）可抑制DEN + PB处理大鼠肝细胞增殖和iNOS表达，降低细胞色素P450含量，抑制CYP 2 E1和CYP 1A 2活性。而且。小檗碱（10、50和100 μ M）在体外抑制DEN加PB处理大鼠的微粒体中的CYP 2 E1和CYP 1A 2的活性，表明小檗碱的抗肝癌潜力可能是由于抑制CYP 2 E1和CYP 1A 2的氧化代谢活性。减少大鼠NO的产生。(C)2007年，Elsevier Masson SAS。All rights reserved.
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.