Steuck Maryvonne, Hellhake Stefan, Schebb Nils Helge
Department of Food Chemistry, University of Wuppertal , Wuppertal, Germany.
Institute for Food Toxicology and Analytical Chemistry, University of Veterinary Medicine Hannover , Hannover, Germany.
J Agric Food Chem. 2016 Nov 30;64(47):8973-8976. doi: 10.1021/acs.jafc.6b04501. Epub 2016 Nov 18.
The product of cytochrome P450 monooxygenase (P450) ω-hydroxylation of arachidonic acid (AA), 20- hydroxyeicosatetraenoic acid (HETE), is a potent vasoconstrictor. Utilizing microsomes as well as individual CYP4 isoforms we demonstrate here that flavonoids can block 20-HETE formation. Apigenin inhibits CYP4F2 with an IC value of 4.6 μM and 20-HETE formation in human liver and kidney microsomes at 2.4-9.8 μM. Interestingly, the structurally similar naringenin shows no relevant effect on the formation of 20-HETE. Based on these in vitro data, it is impossible to evaluate if a relevant blockade of 20-HETE formation can result in humans from intake of polyphenols with the diet. However, the potency of apigenin is comparable to those of P450 inhibitors such as ketoconazole. Moreover, an IC value in the micromolar range is also described for the inhibition of CYP-mediated drug metabolism leading to food-drug interactions. The modulation of the arachidonic acid cascade by food polyphenols therefore warrants further investigation.
细胞色素P450单加氧酶（P450）对花生四烯酸（AA）进行ω-羟化反应的产物20-羟基二十碳四烯酸（HETE）是一种强效血管收缩剂。我们利用微粒体以及单个CYP4亚型在此证明，黄酮类化合物可阻断20-HETE的形成。芹菜素抑制CYP4F2的IC值为4.6 μM，在人肝和肾微粒体中，2.4 - 9.8 μM的芹菜素可抑制20-HETE的形成。有趣的是，结构相似的柚皮素对20-HETE的形成没有相关影响。基于这些体外数据，无法评估饮食中摄入多酚类物质是否会在人体内导致对20-HETE形成的相关阻断。然而，芹菜素的效力与酮康唑等P450抑制剂相当。此外，对于抑制CYP介导的药物代谢导致的食物-药物相互作用，也有微摩尔范围内的IC值描述。因此，食物多酚对花生四烯酸级联反应的调节值得进一步研究。
