Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, Hubei Collaborative Innovation Center for Green Transformation of Bio-resources, Hubei University, Wuhan 430062, China.
Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, Hubei Collaborative Innovation Center for Green Transformation of Bio-resources, Hubei University, Wuhan 430062, China.
Chem Biol Interact. 2017 Jan 5;261:96-102. doi: 10.1016/j.cbi.2016.11.024. Epub 2016 Nov 23.
CYP2B subfamily accounts for 2-10% of total hepatic CYP450 enzymes and participate in the metabolism of around 8% of clinical drugs. Borneol has been widely used in traditional Chinese medicine for thousands of years. There are many studies about borneol-induced promoting penetration role for a number of drugs through various physiologic barriers, whereas there is no report involved the effect of borneol on hepatic CYP2B. The present work studied the in vivo effect of borneol on the expression and activity of rat hepatic CYP2B. The results indicated that the oral administration of borneol (33, 100 and 300 mg/kg/d) to rats for consecutive 7 days increased the hepatic CYP2B1/2 activity by 1.4-, 1.7- and 2.8-fold, hepatic CYP2B1 mRNA expression by 6.3-, 8.7- and 18.1-fold, and hepatic CYP2B1/2 protein expression by 1.2-, 1.9- and 2.6-fold, respectively compared to the control. Additionally, in the borneol pre-dosing (300 mg/kg/d for consecutive 7 days) rats, the increased Cl and decreased AUC of bupropion were observed as compared to the control. Moreover, there were no obvious effects on CAR protein level in rat liver microsome and nucleus following the borneol treatment. Taken together, our observations indicate that borneol is an in vivo inducer of rat hepatic CYP2B with different regulatory mechanism from phenobarbital-like inducers which caused CYP2B induction with CAR activation.
CYP2B 亚家族占总肝 CYP450 酶的 2-10%,参与约 8%的临床药物代谢。龙脑已在中药中使用了数千年。有许多研究表明,龙脑可促进多种药物通过各种生理屏障的渗透作用,而关于龙脑对肝 CYP2B 的影响尚无报道。本工作研究了龙脑在体内对大鼠肝 CYP2B 的表达和活性的影响。结果表明,龙脑(33、100 和 300mg/kg/d)连续口服给药 7 天,使肝 CYP2B1/2 活性分别增加 1.4 倍、1.7 倍和 2.8 倍,肝 CYP2B1mRNA 表达分别增加 6.3 倍、8.7 倍和 18.1 倍,肝 CYP2B1/2 蛋白表达分别增加 1.2 倍、1.9 倍和 2.6 倍,与对照组相比。此外,与对照组相比,在龙脑预给药(300mg/kg/d 连续 7 天)大鼠中,观察到布比卡因的 Cl 增加和 AUC 降低。此外,龙脑处理后大鼠肝微粒体和核中 CAR 蛋白水平无明显变化。综上所述,我们的观察结果表明,龙脑是大鼠肝 CYP2B 的体内诱导剂,与苯巴比妥样诱导剂的调节机制不同,后者通过 CAR 激活引起 CYP2B 诱导。