East China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences; Key and Open Laboratory of Marine and Estuarine Fisheries Resources and Ecology, Ministry of Agriculture, shanghai 200090, China.
Comp Biochem Physiol C Toxicol Pharmacol. 2011 Nov;154(4):360-6. doi: 10.1016/j.cbpc.2011.07.005. Epub 2011 Jul 23.
Berberine has long been considered as an antibiotic candidate in aquaculture. However, studies regarding its effects on drug-metabolizing enzymes in fish are still limited. In the present study, the effects of berberine on cytochrome P4501A (CYP1A) and CYP3A in crucian carp were investigated. Injection of different concentrations of berberine (0, 5, 25, 50, and 100mg/kg) inhibited the CYP1A mRNA expression, thereby inhibiting further the catalytic activity of CYP1A-related ethoxyresorufin-O-deethylase (EROD). Furthermore, both CYP1A expression and EROD activity were further inhibited with increasing berberine concentrations. In addition, the CYP3A expressions at both the mRNA and the protein levels were downregulated by higher berberine concentrations. The catalytic activity of CYP3A-related erythromycin N-demethylase (ERND) was also inhibited by berberine at a dose of no less than 25mg/kg. Moreover, at the berberine concentration exceeding 25mg/kg, the inhibition of CYP3A expression and ERND activity increased with increasing berberine concentrations. In vitro experiments were also performed. When berberine was pre-incubated with the crucian carp liver microsomes, it competitively inhibited the corresponding EROD activity with the IC(50) of 11.7 μM. However, the ERND activity was slightly inhibited by berberine with the IC(50) of 206.4 μM. These results suggest that, in crucian carp, berberine may be a potent inhibitor to CYP1A, whereas the CYP3A inhibition needs a higher concentration of berberine.
小檗碱长期以来一直被认为是水产养殖中的一种抗生素候选药物。然而，关于其对鱼类药物代谢酶的影响的研究仍然有限。在本研究中，研究了小檗碱对鲫鱼细胞色素 P4501A（CYP1A）和 CYP3A 的影响。注射不同浓度的小檗碱（0、5、25、50 和 100mg/kg）抑制了 CYP1A mRNA 的表达，从而进一步抑制了 CYP1A 相关的乙氧基试卤灵-O-去乙基酶（EROD）的催化活性。此外，随着小檗碱浓度的增加，CYP1A 的表达和 EROD 活性进一步受到抑制。此外，较高浓度的小檗碱下调了 CYP3A 在 mRNA 和蛋白质水平的表达。CYP3A 相关红霉素 N-脱甲基酶（ERND）的催化活性也被小檗碱抑制，抑制浓度不低于 25mg/kg。此外，当小檗碱浓度超过 25mg/kg 时，CYP3A 表达和 ERND 活性的抑制作用随着小檗碱浓度的增加而增加。还进行了体外实验。当小檗碱与鲫鱼肝微粒体预孵育时，它以 11.7μM 的 IC（50）竞争性抑制相应的 EROD 活性。然而，小檗碱对 ERND 活性的抑制作用较小，IC（50）为 206.4μM。这些结果表明，在鲫鱼中，小檗碱可能是 CYP1A 的一种有效抑制剂，而 CYP3A 的抑制需要更高浓度的小檗碱。
