Research Group for Pharmaceutical Activities of Natural Products using Pharmaceutical Biotechnology (PANPB), Faculty of Pharmaceutical Sciences, National Research University - Khon Kaen University, Khon Kaen 40002, Thailand.
Chem Biol Interact. 2012 Mar 5;196(1-2):23-9. doi: 10.1016/j.cbi.2012.01.006. Epub 2012 Feb 8.
Berberine, an isoquinoline alkaloid isolated from medicinal plants such as Berberis aristata, Coptis chinesis, Coptis japonica, Coscinium fenestatun, and Hydrastis Canadensis, is widely used in Asian countries for the treatment of diabetes, hypertension, and hypercholesterolemia. Interaction between berberine and the cytochrome P450 enzymes (CYPs) has been extensively reported, but there are only a few reports of this interaction in the diabetic state. In this study, the effect of berberine on the mRNA of the CYPs in primary mouse hepatocytes and in streptozotocin (STZ)-induced diabetic mice was investigated. In primary mouse hepatocytes, berberine suppressed the induction of Cyp1a1, Cyp1a2, Cyp2e1, Cyp3a11, Cyp4a10, and Cyp4a14 mRNA expression by their prototypical inducers in a concentration-dependent fashion. However, berberine treatment alone increased the expression of Cyp2b9 and Cyp2b10 mRNA. In vivo, berberine showed the same hypoglycemic activity as metformin, an established hypoglycemic drug. The hepatic mRNA levels of Cyp1a1, Cyp2b9, Cyp2b10, Cyp3a11, Cyp4a10, and Cyp4a14 were increased in STZ-induced diabetic mice. Interestingly, berberine itself suppressed the expression of Cyp2e1, an adverse hepatic event-associated enzyme, while the expression of Cyp3a11, Cyp4a10, and Cyp4a14 were restored to normal levels by berberine. In conclusion, berberine has the potential to modify the expression of CYPs by either suppression or enhancement of CYPs' levels. Consumption of berberine as an anti-hyperglycemic compound by diabetic patients might provide an extra benefit due to its potential to restore the expression of Cyp2e1, Cyp3a, and Cyp4a to normal levels. However, an herb-drug interaction might be of concern since any berberine-containing product would definitely cause pronounced interactions based on CYP3A4 inhibition.
小檗碱是一种从小檗属植物、黄连、日本黄连、木防己和加拿大黄连等药用植物中分离出来的异喹啉生物碱，在亚洲国家被广泛用于治疗糖尿病、高血压和高胆固醇血症。小檗碱与细胞色素 P450 酶（CYPs）之间的相互作用已被广泛报道，但在糖尿病状态下，这种相互作用的报道很少。在这项研究中，研究了小檗碱对原代小鼠肝细胞和链脲佐菌素（STZ）诱导的糖尿病小鼠中 CYP 基因的 mRNA 的影响。在原代小鼠肝细胞中，小檗碱以浓度依赖性方式抑制其典型诱导剂诱导的 Cyp1a1、Cyp1a2、Cyp2e1、Cyp3a11、Cyp4a10 和 Cyp4a14 mRNA 表达的诱导。然而，小檗碱单独处理会增加 Cyp2b9 和 Cyp2b10 mRNA 的表达。在体内，小檗碱表现出与二甲双胍（一种已确立的降血糖药物）相同的降血糖活性。STZ 诱导的糖尿病小鼠肝组织 Cyp1a1、Cyp2b9、Cyp2b10、Cyp3a11、Cyp4a10 和 Cyp4a14 的 mRNA 水平升高。有趣的是，小檗碱本身抑制了 Cyp2e1 的表达，Cyp2e1 是一种与肝不良事件相关的酶，而 Cyp3a11、Cyp4a10 和 Cyp4a14 的表达则被小檗碱恢复到正常水平。总之，小檗碱通过抑制或增强 CYP 水平来调节 CYP 的表达。糖尿病患者将小檗碱作为一种抗高血糖化合物服用，可能会因恢复 Cyp2e1、Cyp3a 和 Cyp4a 的表达而获得额外的益处。然而，由于任何含有小檗碱的产品肯定会基于 CYP3A4 抑制而引起明显的相互作用，因此草药-药物相互作用可能是一个关注点。
