山奈酚和槲皮素对大鼠细胞色素P450酶活性的影响

目的:观察山奈酚和槲皮素两种银杏黄酮对细胞色素P450的影响。方法:原代培养大鼠肝细胞,接触0.1~10.0μm o l/L的山奈酚或槲皮素,作用12 h、24 h和48 h,用N ash法检测细胞色素P450同工酶-红霉素N-脱甲基酶(ENRD)和氨基比林N-脱甲基酶(ADM)的活性。分别以红霉素(10.0μm o l/L)和二甲基亚砜(DM SO)作为阳性对照和溶剂对照。结果:0.1、1.0和10.0μm o l/L山奈酚作用24 h,ENRD酶活性分别为(0.088±0.008)、(0.074±0.006)和(0.041±0.003)μm o l/(m g.m in-1);槲皮素相同浓度和作用时间处理的ENRD酶活性分别为(0.082±0.007)、(0.063±0.007)和(0.034±0.005)μm o l/(m g.m i-n 1)。其中1.0和10.0μm o l/L山奈酚和槲皮素处理的肝细胞ENRD酶活性都显著低于溶剂对照组(0.085±0.011)μm o l/(m g.m in-1),且呈剂量-效应关系(P<0.01)。10μm o l/L山奈酚处理细胞12 h和48 h后,ENRD酶活性为(0.053±0.006)和(0.037±0.007)μm o l/(m g.m i-n 1);10μm o l/L槲皮素处理细胞12 h和48 h后,ENRD酶活性为(0.067±0.005)和(0.032±0.004)μm o l/(m g.m i-n 1),都具有明显的时间-效应关系(P<0.01)。山奈酚只有在10μm o l/L浓度下作用24 h对ADM活性出现抑制,槲皮素对ADM活性没有明显影响。结论:在本实验条件下,山奈酚和槲皮素能明显抑制大鼠肝细胞ENRD活性;山奈酚在10μm o l/L浓度下能轻度抑制ADM,而槲皮素对ADM活性没有明显的抑制作用。

Effects of kaempferol and quercetin on cytochrome 450 activities in primarily cultured rat hepatocytes

OBJECTIVE: To observe the effects of kaempferol and quercetin on the activity of cytochrome P450 in rat hepatocytes. METHODS: Primarily cultured rat hepatocytes were exposed to kaempferol or quercetin in concentrations of 0.1, 1, 10 micromol/L for 12 h, 24 h and 48 h. Hepatocytes CYP isoemzymes-erythromycin N-demethylase (ERND) and aminopyrine N-demethylase (ADM) activities were determined by Nash methods. Erythromycin (10 micromol/L) was used as positive control and DMSO(0.1%) as solvent control. RESULTS: Kaempferol and quercetin inhibited ENRD activity in a dose-and time-dependent manner. In dose-response study, the ENRD activities in kaempferol (0.1,1 and 10 micromol/L) treated groups were (0.088+/-0.008), (0.074+/-0.006) and (0.041+/-0.003)micromol/(mg.min(-1)), respectively. ENRD activity in quercetin treated groups at the same concentrations were (0.082+/-0.007), (0.063+/-0.007) and (0.034+/-0.005) micromol/(mg.min(-1)), respectively. In time-courses study, the ENRD activity exposed to 10 micromol/L kaempferol or quercetin for 12 h and 48 h were (0.053+/-0.006) and (0.037+/-0.007) micromol/(mg.min(-1)), or (0.067+/-0.005) and (0.032+/-0.004) micromol/(mg.min(-1)). ADM activity was inhibited only by kaempferol in 10 mol/L at 24 h, but was not significantly altered by quercetin at any concentration tested. CONCLUSION: In the present condition, kaempferol and quercetin act as potential CYP3A4 inhibitors as they can significantly inhibit ENRD in primarily cultured rat hepatocytes.