Metabolism of most endogenous and exogenous compounds is usually produced by the oxidation of cytochrome P450. Due to drug-drug interactions caused by the inhibition or induction of cytochrome P450 enzymes, changes in drug metabolism are the major causes of drug toxicity, CYP3A4 is one of the key isozymes, and involved in the metabolism of over 60% of clinical drugs. Human ether-a-go-go related genes (hERG) potassium channel is the most important target of many drugs and plays an important role in cardiac repolarization. Blockade of this channel may lead to long QT syndrome (LQTS), leading to sudden cardiac death. Therefore, it is necessary to evaluate the inhibitory properties of drugs on cytochrome P450 enzymes and hERG channel. We primarily evaluate the safety of berberine in combination with statins. Based on these findings, berberine in combination with statins has a greater inhibitory effect on CYP3A4 activity and CYP3A4 protein and mRNA expression than berberine alone. Simvastatin and atorvastatin reduce hERG current by accelerating channel inactivation. At the same time, the inhibitory effect of berberine and statin combination increased on hERG current by reducing the time constant of inactivation than the single drug alone. These results indicate that berberine in combination with statins can increase cardiotoxicity by inhibiting CYP3A4 and hERG channel.

大多数内源性和外源性化合物的代谢通常是通过细胞色素P450的氧化而产生的。由于细胞色素P450酶的抑制或诱导引起的药物-药物相互作用，药物代谢的变化是药物毒性的主要原因，CYP3A4是关键的同工酶之一，并参与了60％以上的临床药物的代谢。人源不断的相关基因（hERG）钾通道是许多药物中最重要的靶标，并且在心脏复极中起着重要的作用。阻塞该通道可能导致长时间的QT综合征（LQTS），从而导致心源性猝死。因此，有必要评估药物对细胞色素P450酶和hERG通道的抑制特性。我们主要评估黄连素与他汀类药物合用的安全性。根据这些发现，小ber碱联合他汀类药物比小than碱对CYP3A4活性和CYP3A4蛋白和mRNA表达有更大的抑制作用。辛伐他汀和阿托伐他汀通过加速通道失活来降低hERG电流。同时，小alone碱和他汀类药物组合的抑制作用比单独使用一种药物降低了灭活的时间常数，从而增加了对hERG的抑制作用。这些结果表明，小ber碱与他汀类药物合用可通过抑制CYP3A4和hERG通道而增加心脏毒性。与单独使用单一药物相比，黄连素和他汀类药物联合的抑制作用通过降低失活时间常数而增加了对hERG电流的抑制作用。这些结果表明，小ber碱与他汀类药物合用可通过抑制CYP3A4和hERG通道而增加心脏毒性。与单独使用单一药物相比，黄连素和他汀类药物联合的抑制作用通过降低失活时间常数而增加了对hERG电流的抑制作用。这些结果表明，小ber碱与他汀类药物合用可通过抑制CYP3A4和hERG通道而增加心脏毒性。