Cui Han-Ming, Zhang Qiu-Yan, Wang Jia-Long, Chen Jian-Long, Zhang Yu-Ling, Tong Xiao-Lin
Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China.
Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China.
J Ethnopharmacol. 2014 Dec 2;158 Pt A:388-96. doi: 10.1016/j.jep.2014.10.018. Epub 2014 Oct 31.
Berberine (BER) and BER-original herbal medicines have a variety of pharmacological functions and have been widely used in clinical. However, its effect of enzyme induction on cytochrome P450 (CYP) in human hepatocytes is unknown.
Metabolism of berberine and its effect on main metabolic enzymes in HepG2 cell in vitro was investigated. Cocktail probe drugs, mRNA expression and protein expression were used to evaluate the metabolism potency. Meanwhile, an UPLC-MS/MS method was validated for the analysis of BER and four probe drugs in HepG2 cell.
BER significantly increased the metabolism of midazolam, phenacetin and tolbutamide by inducing the CYP1A2 and 3A4 enzyme in a dose-dependent manner, the mRNA and protein expression of CYP1A2 and 3A4 were increased by berberine at 1000ng·mL(-1). The activity of CYP1A2 and 3A4 could be induced by BER more than 500ng·mL(-1) in HepG2 cell, which was confirmed by the increase of its mRNA and protein expression.
BER increases the metabolism of cocktail drugs such as midazolam, phenacetin and tolbutamide by increasing the mRNA and protein expression of CYP1A2 and 3A4.
黄连素（BER）及含黄连素的原生草药具有多种药理功能，已在临床上广泛应用。然而，其对人肝细胞中细胞色素P450（CYP）的酶诱导作用尚不清楚。
研究了黄连素在体外对HepG2细胞的代谢及其对主要代谢酶的影响。采用鸡尾酒探针药物、mRNA表达和蛋白质表达来评估代谢能力。同时，验证了一种超高效液相色谱-串联质谱法用于分析HepG2细胞中的黄连素和四种探针药物。
黄连素通过剂量依赖性诱导CYP1A2和3A4酶，显著增加了咪达唑仑、非那西丁和甲苯磺丁脲的代谢，在1000ng·mL(-1) 时黄连素使CYP1A2和3A4的mRNA和蛋白质表达增加。在HepG2细胞中，500ng·mL(-1) 以上的黄连素可诱导CYP1A2和3A4的活性，这通过其mRNA和蛋白质表达的增加得到证实。
黄连素通过增加CYP1A2和3A4的mRNA和蛋白质表达，增加了咪达唑仑、非那西丁和甲苯磺丁脲等鸡尾酒药物的代谢。
