Pungent ginger components modulates human cytochrome P450 enzymes in vitro  

作　　者：Mian Li Pei-zhan Chen Qing-xi Yue Jing-quan Li Rui-ai Chu Wei Zhang Hui Wang 

机构地区：[1]Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences University of the Chinese Academy of Sciences, Shanghai 200031, China [2]Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing 100021, China [3]National Center for Food Safety and Technology, Illinois Institute of Technology, Summit, IL 60501, USA

出　　处：《Acta Pharmacologica Sinica》2013年第9期1237-1242,共6页中国药理学报（英文版）

基　　金：We thank Ms Yuan-yuan DAI at the Cancer Hospital/Institute, Chinese Academy of Medical Sciences, for her generous gift of sulfaphenazole. This study was supported by grants from the One Hundred Talents Program and Knowledge Innovation Program （KSCX2-EW-R-10） of the Chinese Academy of Sciences, the National Natural Science Foundation （81125020, 91029715, 31070680, 31101261, 81242002, and 31200569）, the Ministry of Science and Technology of China （2012BAK01B00, 2011BAK10B00, and 2009CB919000）, the Science and Technol- ogy Commission of Shanghai Municipality （12XD1407000, 12431900500, and 10391902100）, and Xuhui Central Hospital （CRC2011001 and CRC2011004）, Director Foundation （20090101） and the Food Safety Research Center and Key Laboratory of Nutrition and Metabolism of INS, SIBS, CAS. Pei-zhan CHEN and Qing-xi YUE were partially supported by the SA-SIBS scholarship program.

摘　　要：Aim： Ginger rhizome is used worldwide as a spicy flavor agent. This study was designed to explore the potential effects of pungent ginger components, 6-, 8-, and 10-gingerol, on human cytochrome P450 （CYP450） enzymes that are responsible for the metabolism of many prescription drugs.Methods： The activities of human CYP2C9, CYP2C19, CYP2D6, and CYP3A4 were analyzed using Vivid P450 assay kits. The mRNA expression of CYP3A4 in human hepatocellular carcinoma cell line HepG2 was measured using quantitative real-time PCR assay.Results： All three gingerols potently inhibited CYP2C9 activity, exerted moderate inhibition on CYP2C19 and CYP3A4, and weak inhibion on CYP2D6. 8-Gingerol was the most potent in inhibition of P450 enzymes with IC50 values of 6.8, 12.5, 8.7, and 42.7 μmol/L for CYP2C9, CYP2C19, CYP3A4, and CYP2D6, respectively. By comparing the effects of gingerols on CYP3A4 with three different fluorescent substrate probes, it was demonstrated that the inhibition of gingerols on CYP3A4 had no substrate-dependence. In HepG2 cells, 8-gingerol and 10-gingerol inhibited, but 6-gingerol induced mRNA expression of CYP3A4.Conclusion： 6-, 8-, and 10-gingerol suppress human cytochrome P450 activity, while 8- and 10-gingerol inhibit CYP3A4 expression. The results may have an implication for the use of ginger or ginger products when combined with therapeutic drugs that are metabolized by cytochrome P450 enzymes.Aim： Ginger rhizome is used worldwide as a spicy flavor agent. This study was designed to explore the potential effects of pungent ginger components, 6-, 8-, and 10-gingerol, on human cytochrome P450 （CYP450） enzymes that are responsible for the metabolism of many prescription drugs.Methods： The activities of human CYP2C9, CYP2C19, CYP2D6, and CYP3A4 were analyzed using Vivid P450 assay kits. The mRNA expression of CYP3A4 in human hepatocellular carcinoma cell line HepG2 was measured using quantitative real-time PCR assay.Results： All three gingerols potently inhibited CYP2C9 activity, exerted moderate inhibition on CYP2C19 and CYP3A4, and weak inhibion on CYP2D6. 8-Gingerol was the most potent in inhibition of P450 enzymes with IC50 values of 6.8, 12.5, 8.7, and 42.7 μmol/L for CYP2C9, CYP2C19, CYP3A4, and CYP2D6, respectively. By comparing the effects of gingerols on CYP3A4 with three different fluorescent substrate probes, it was demonstrated that the inhibition of gingerols on CYP3A4 had no substrate-dependence. In HepG2 cells, 8-gingerol and 10-gingerol inhibited, but 6-gingerol induced mRNA expression of CYP3A4.Conclusion： 6-, 8-, and 10-gingerol suppress human cytochrome P450 activity, while 8- and 10-gingerol inhibit CYP3A4 expression. The results may have an implication for the use of ginger or ginger products when combined with therapeutic drugs that are metabolized by cytochrome P450 enzymes.

关 键 词：ginger rhizome GINGEROL cytochrome P450 enzyme system CYP2C9 CYP2C19 CYP3A4 CYP2D6 dietary supplements drug-diet interactions 

分 类 号：Q513[生物学—生物化学] TQ467.6[化学工程—制药化工]