Manthey John A, Buslig Béla S
Citrus and Subtropical Products Laboratory, Agricultural Research Service, US Department of Agriculture, Winter Haven, Florida 33881, USA.
J Agric Food Chem. 2005 Jun 29;53(13):5158-63. doi: 10.1021/jf058004g.
The reported effects of grapefruit (Citrus paradisi Macf.) juice on oral bioavailability of certain prescription drugs have led to the discovery of the inhibition by compounds in grapefruit of cytochrome P450 3A4 (CYP3A4) in the intestinal wall and liver. Recent evidence indicates that furanocoumarins related to bergamottin [5-[(3',7'-dimethyl-2',6'-octadienyl)oxy]psoralen] are primarily responsible for the grapefruit effect, yet the exact mechanisms and roles that specific compounds play in this effect are still uncertain. In the current experiments freshly extracted grapefruit juice was separated into four fractions, consisting of raw finished juice (approximately 5% fine pulp), centrifugal retentate (approximately 35% fine pulp), centrifuged supernatant (<1% pulp), and coarse finisher pulp. The relative concentrations of furanocoumarins in each of these grapefruit juice fractions were measured by HPLC-MS. These measurements showed that the centrifugal retentate had the highest furanocoumarin content, containing 892 ppm of bergamottin, 628 ppm of 6',7'-dihydroxybergamottin, 116 ppm of 6',7'-epoxybergamottin, 105 ppm of 7-geranyloxycoumarin, and approximately 467 ppm of furanocoumarin dimers. These high furanocoumarin concentrations make this fraction a useful starting material for preparative-scale isolations of these compounds. MS analysis of this furanocoumarin-enriched fraction provided evidence of additional furanocoumarins in grapefruit juice that remain to be fully characterized and evaluated for their roles in the grapefruit-drug interactions.
据报道，葡萄柚（Citrus paradisi Macf.）汁对某些处方药口服生物利用度的影响，促使人们发现葡萄柚中的化合物可抑制肠壁和肝脏中的细胞色素P450 3A4（CYP3A4）。最近的证据表明，与佛手柑内酯[5-[(3',7'-二甲基-2',6'-辛二烯基)氧基]补骨脂素]相关的呋喃香豆素是造成葡萄柚效应的主要原因，但特定化合物在这种效应中所起的确切机制和作用仍不确定。在当前实验中，将新鲜提取的葡萄柚汁分离成四个部分，包括原汁成品（约5%细果肉）、离心截留物（约35%细果肉）、离心上清液（<1%果肉）和粗制果肉。通过HPLC-MS测定这些葡萄柚汁部分中呋喃香豆素的相对浓度。这些测量结果表明，离心截留物的呋喃香豆素含量最高，含有892 ppm的佛手柑内酯、628 ppm的6',7'-二羟基佛手柑内酯、116 ppm的6',7'-环氧佛手柑内酯、105 ppm的7-香叶氧基香豆素和约467 ppm的呋喃香豆素二聚体。这些高浓度的呋喃香豆素使该部分成为这些化合物制备规模分离的有用起始材料。对该富含呋喃香豆素的部分进行MS分析，为葡萄柚汁中仍有待充分表征和评估其在葡萄柚-药物相互作用中作用的其他呋喃香豆素提供了证据。
