食品-药品相互作用可影响药物疗效和毒性，是当前营养学研究的热点之一。柚皮苷、柚皮素在葡萄柚汁、橙汁等多种食物中含有，对于其是否会通过影响CYP450酶活性而与药物发生相互作用，至今未有公认的结论。本项目采用人和大鼠基因重组肝微粒体CYP450同工酶、大鼠和人肝微粒体、大鼠和人肠微粒体、大鼠肝细胞、人HepaRG细胞等体外模型和大鼠在体模型，评价柚皮苷、柚皮素在体内外对CYP450酶亚型的调控作用；采用核受体双荧光报告基因、miRNAs基因高表达或沉默的HepG2细胞等体外模型和人源化核受体基因、miRNAs基因敲入或敲除的小鼠体内模型，考察柚皮苷、柚皮素对CYP450酶亚型的调控作用与核受体、miRNAs调控的关系，最终阐明其调控CYP450酶的机制。该项目为阐明柚皮苷、柚皮素是否与药物发生相互作用这一重要问题提供系统的科学依据，对减少由于饮食不当而引起药源性损害具有重要意义。

Food and drug interactions can affect drug efficacy and toxicity, and is one of hot topics amongst current nutrition research. A lot of food including grapefruit juice and orange juice contain both naringin and naringenin. Untill now, it is uncertain whether naringin or naringenin interact with drugs through regulating CYP450 enzyme activity. In this project, rat model and a series of in vitro models, including recombinant cytochrome P450 (CYP450) isoenzymes, liver and intestinal microsomes, liver cells and HepaRG cells will be used to evaluate the effects of naringin or naringenin on CYP450 enzyme activity. In order to clarifty the mechanisms of actions, transient cotransfection reporter gene systems using two autofluorescent reporter genes, HepG2 cell model with overexpression or silence of miRNAs, nuclear receptor or miRNA gens knock-out or knock- in animal models will be used to investigate whether the effects of naringin or naringenin on CYP450 activity are related to regulating miRNAs and nuclear receptor pathways. This project will provide scientific proof if naringin or naringenin will interact with drugs and will be of benefit to the reduction of drug-induced damage caused by improper diet.