Ishihara Masaru, Toda Hikaru, Sunagane Nobuyoshi, Ohta Takafumi
Faculty of Pharmaceutical Sciences, Tokyo University of Science (RIKADAI), Noda, Chiba, Japan.
Yakugaku Zasshi. 2011;131(5):679-84. doi: 10.1248/yakushi.131.679.
Furanocoumarins (FCs) such as bergamottin (BG) and 6',7'-dihydroxybergamottin (DHBG) contained in grapefruits are known to be cytochrome P450 3A4 (CYP3A4) inhibitors. These are contained in larger quantity in peel than in pulp, and therefore, processed peel products possibly have strong CYP3A4 inhibitory activity. The CYP3A4 inhibitory potency of these processed peel products, however, remains to be elucidated. The FC content and CYP3A inhibitory activities of various processed fruit peel products were investigated. CYP3A inhibitory activities of crystallized grapefruit peel, grapefruit marmalade, lemon peel and bitter orange slice were close to that of 100% grapefruit juice, while the activities of yuzu slice, pomelo (buntan) marmalade and crystallized iyokan peel were very weak, 1/8-1/20 of 100% grapefruit juice. The maximum BG content was 5.6 µg/g in lemon peel. The maximum DHBG content was 7.2 µg/g in crystallized grapefruit peel, about 1/30 that of raw peel. Grapefruit marmalade and crystallized grapefruit peel contained similar amounts of FCs to 100% grapefruit juice, but FCs were not detected in pomelo (buntan) marmalade or crystallized iyokan peel. Good correlation (r=0.78) was observed between the FC contents of these peel products and those CYP3A inhibitory activities. Preparation of homemade grapefruit marmalade and crystallized peel revealed that considerably lower DHBG content in these products and lower CYP3A inhibitory activity than anticipated were attributable to outflow of DHBG to broth during boiling of the raw peel.
葡萄柚中含有的呋喃香豆素（FCs），如佛手柑内酯（BG）和6'，7'-二羟基佛手柑内酯（DHBG），已知是细胞色素P450 3A4（CYP3A4）抑制剂。这些物质在果皮中的含量比果肉中更高，因此，加工后的果皮产品可能具有较强的CYP3A4抑制活性。然而，这些加工果皮产品的CYP3A4抑制效力仍有待阐明。研究了各种加工水果果皮产品的FC含量和CYP3A抑制活性。结晶葡萄柚皮、葡萄柚果酱、柠檬皮和苦橙片的CYP3A抑制活性与100%葡萄柚汁相近，而柚子片、柚子（文旦）果酱和结晶伊予柑皮的活性非常弱，仅为100%葡萄柚汁的1/8 - 1/20。柠檬皮中BG的最大含量为5.6μg/g。结晶葡萄柚皮中DHBG的最大含量为7.2μg/g，约为生果皮的1/30。葡萄柚果酱和结晶葡萄柚皮中的FC含量与100%葡萄柚汁相似，但柚子（文旦）果酱或结晶伊予柑皮中未检测到FC。这些果皮产品的FC含量与CYP3A抑制活性之间存在良好的相关性（r = 0.78）。自制葡萄柚果酱和结晶果皮的制备表明这些产品中DHBG含量显著降低以及CYP3A抑制活性低于预期，这是由于生果皮煮沸过程中DHBG流入肉汤所致。
