银杏叶提取物及其黄酮类单体对ChangLiver细胞中CYP3A4和CYP2C9的影响

目的研究银杏叶提取物（GBE）及其黄酮类单体槲皮素和山柰酚对Chang Liver细胞CYP3A4、CYP2C9表达的影响。方法 CCK-8法检测GBE、槲皮素、山柰酚对Chang Liver细胞增殖的抑制作用;RT-PCR方法检测其不同浓度对Chang Liver细胞中CYP3A4 mRNA、CYP2C9 mRNA表达的影响;Western blot方法测定CYP3A4、CYP2C9蛋白表达的相对含量。结果 GBE呈浓度依赖性地诱导CYP3A4 mRNA和蛋白的表达,对CYP2C9mRNA和蛋白的表达没有显著作用;槲皮素对CYP3A4 mRNA和蛋白的表达有较明显的诱导作用,呈浓度依赖性地抑制CYP2C9 mRNA和蛋白的表达;山柰酚呈浓度依赖性地抑制细胞中CYP3A4 mRNA和蛋白的表达,对CYP2C9 mRNA和蛋白的表达没有显著影响。结论 GBE、槲皮素、山柰酚对Chang Liver细胞中CYP3A4、CYP2C9的表达具有不同的影响作用,这些结果为GBE与其他药物相互作用提供理论基础,提高联合用药的有效性及安全性,为黄酮类单体新药开发提供参考信息和理论依据。

Effect of GBE and its flavonoids on CYP3A4 and CYP2C9 expressions in Chang Liver cells

Objective To study the effect of GBE and its flavonoids（quercetin and kaempferol） on CYP3A4 and CYP2C9 expressions in Chang Liver cells. Methods CCK-8 assay was performed to determine the proliferation of Chang Liver cells after treatment with GBE, quercetin and kaempferol. RT-PCR and Western blot were performed to examine the CYP3A4 and CYP2C9 mRNA and protein expressions respectively. Results Expressions of CYP3A4 mRNA and protein were significantly induced by treatment with GBE at 3 concentrations for 48 h in Chang Liver cells（P 0.05）. GBE had no significant effect on the expression of CYP2C9 mRNA and protein. Quercetin can obviously induce the expression of CYP3A4 mRNA and protein, while it can inhibit the expression of CYP2C9 mRNA and protein（P 0.05）. Kaempferol can significantly inhibit the expression of CYP3A4 mRNA and has no significant effect on the expression of CYP2C9 mRNA and protein. Conclusion GBE, quercetin and kaempferol have different effects on CYP3A4 and CYP2C9 in Chang Liver cells. The experimental data help to understand the mechanism of GBE and its flavonoids on CYP3A4 and CYP2C9, and support future drug development of these compounds in its clinical therapies.