Gao Li-Na, Zhang Ye, Cui Yuan-Lu, Yan Kuo
Research Center of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China; Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
Research Center of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China; Department of Pharmaceutical Sciences, Zibo Vocational Institute, Zibo, Shandong 255314, China.
Fitoterapia. 2014 Oct;98:130-6. doi: 10.1016/j.fitote.2014.07.018. Epub 2014 Jul 27.
Genipin is obtained from the fruit of Gardenia jasminoides Ellis and acts as an herbal medicine or functional food in East Asia. In addition to produce natural colorant, it possesses widely antiinflammatory, antithrombotic, antidepressive and anticarcinogenic activities. However, little research focuses on the potential of genipin for drug-drug interactions. In this study, effects of genipin on mRNA and protein expression of cytochrome P450 (CYP) 2C19, CYP2D6 and CYP3A4 were detected by real-time reverse-transcription polymerase chain reaction (real-time RT-PCR) and Western blot, respectively, in human hepatoma HepG2 cells. Enzyme activities of which were detected by luminogenic CYP assay in vitro. Moreover, effect of genipin on P-glycoprotein expression was analyzed by Western blot. Results showed that genipin possessed a significant induction on CYP2D6 and a remarkable inhibition on CYP2C19 and CYP3A4 not only from the expression of mRNA and protein (P<0.05 or P<0.01), but the level of enzyme activity. Moreover, a concentration-dependent induction of genipin on P-glycoprotein expression was observed. In conclusion, caution should be exercised with respect to the induction or inhibition of genipin on CYP isoenzymes and the strong induction on P-glycoprotein.
京尼平是从栀子果实中提取的，在东亚地区用作草药或功能性食品。除了生产天然色素外，它还具有广泛的抗炎、抗血栓形成、抗抑郁和抗癌活性。然而，很少有研究关注京尼平在药物相互作用方面的潜力。在本研究中，分别通过实时逆转录聚合酶链反应（实时RT-PCR）和蛋白质印迹法检测了京尼平对人肝癌HepG2细胞中细胞色素P450（CYP）2C19、CYP2D6和CYP3A4的mRNA和蛋白质表达的影响。通过体外荧光素酶CYP测定法检测其酶活性。此外，通过蛋白质印迹法分析了京尼平对P-糖蛋白表达的影响。结果表明，京尼平不仅对CYP2D6有显著诱导作用，对CYP2C19和CYP3A4有显著抑制作用，且在mRNA和蛋白质表达水平上（P<0.05或P<0.01），在酶活性水平上也是如此。此外，还观察到京尼平对P-糖蛋白表达有浓度依赖性诱导作用。总之，应注意京尼平对CYP同工酶的诱导或抑制作用以及对P-糖蛋白的强烈诱导作用。
