Department of Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche ed Ambientali, Università di Messina, Viale F. Stagno d'Alcontres 31, 98166 Messina, Italy.
Food Chem. 2020 Jul 30;319:126578. doi: 10.1016/j.foodchem.2020.126578. Epub 2020 Mar 10.
For clementine juice, previous data indicate a possible food-drug interaction with substrates of key enzymes responsible for drug metabolism (i.e. cytochrome P450 [CYP] 3A4, CYP1A2). However, which compounds in clementine juice are responsible for these effects are unknown. Therefore, we aimed to identify the compounds in clementine juice provoking metabolic enzyme inhibition or induction. The results demonstrated that the flavonoid fraction of clementine juice provoked induction of several genes and inhibition of both CYP3A4 and CYP1A2, matching effects observed with whole clementine juice. CYP1A2 inhibition and induction can most likely be attributed to nobiletin, sinensetin, and tangeretin. Tangeretin was the only compound causing CYP3A4 induction while CYP3A4 inhibition was most likely the result of additive or synergistic effects caused by several compounds. Thus, whenever evaluating the clinical relevance of clementine interactions, flavonoid contents should be reported because these might explain differences between cultivars and harvests.
对于克莱门氏小柑橘汁，先前的数据表明，它可能与负责药物代谢的关键酶（即细胞色素 P450 [CYP] 3A4、CYP1A2）的底物发生食物-药物相互作用。然而，克莱门氏小柑橘汁中哪些化合物是造成这些影响的原因尚不清楚。因此，我们旨在确定克莱门氏小柑橘汁中引起代谢酶抑制或诱导的化合物。结果表明，克莱门氏小柑橘汁的类黄酮部分可引起多个基因的诱导以及 CYP3A4 和 CYP1A2 的抑制，与整个克莱门氏小柑橘汁观察到的效果一致。CYP1A2 的抑制和诱导很可能归因于诺必特、辛弗林和橘红素。橘红素是唯一引起 CYP3A4 诱导的化合物，而 CYP3A4 的抑制很可能是由几种化合物的相加或协同作用所致。因此，在评估克莱门氏小柑橘汁相互作用的临床相关性时，应报告类黄酮含量，因为这可能解释不同品种和收获期之间的差异。
