title: Evaluation of the in vitro/in vivo potential of five berries (bilberry, blueberry, cranberry, elderberry, and raspberry ketones) commonly used as herbal supplements to inhibit uridine diphospho-glucuronosyltransferase.
abstract: In this study, we evaluated inhibitory potentials of popularly-consumed berries (bilberry, blueberry, cranberry, elderberry, and raspberry ketones) as herbal supplements on UGT1A1, UGT1A4, UGT1A6, UGT1A9, and UGT2B7 in vitro. We also investigated the potential herb-drug interaction via UGT1A1 inhibition by blueberry in vivo. We demonstrated that these berries had only weak inhibitory effects on the five UGTs. Bilberry and elderberry had no apparent inhibitions. Blueberry weakly inhibited UGT1A1 with an IC50 value of 62.4±4.40 μg/mL and a Ki value of 53.1 μg/mL. Blueberry also weakly inhibited UGT2B7 with an IC50 value of 147±11.1 μg/mL. In addition, cranberry weakly inhibited UGT1A9 activity (IC50=458±49.7 μg/mL) and raspberry ketones weakly inhibited UGT2B7 activity (IC50=248±28.2 μg/mL). Among tested berries, blueberry showed the lowest IC50 value in the inhibition of UGT1A1 in vitro. However, the co-administration of blueberry had no effect on the pharmacokinetics of irinotecan and its active metabolite, SN-38, which was mainly eliminated via UGT1A1, in vivo. Our data suggests that these five berries are unlikely to cause clinically significant herb-drug interactions mediated via inhibition of UGT enzymes involved in drug metabolism. These findings should enable an understanding of herb-drug interactions for the safe use of popularly-consumed berries.
authors.affiliation: College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon 420-743, Republic of Korea.
authors.forename: Eu Jin
authors.initials: EJ
authors.lastname: Choi
authors.affiliation: College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon 420-743, Republic of Korea.
authors.forename: Jung Bae
authors.initials: JB
authors.lastname: Park
authors.affiliation: College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon 420-743, Republic of Korea.
authors.forename: Kee Dong
authors.initials: KD
authors.lastname: Yoon
authors.affiliation: College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon 420-743, Republic of Korea. Electronic address: baesk@catholic.ac.kr.
authors.forename: Soo Kyung
authors.initials: SK
authors.lastname: Bae
mesh_terms: D000818:Animals; D029798:Blueberry Plants / Q000737:chemistry; D002074:Butanones / Q000494:pharmacology; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D002853:Chromatography, Liquid; D005638:Fruit / Q000737:chemistry*; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D041743:Herb-Drug Interactions; D006801:Humans; D020128:Inhibitory Concentration 50; D000077146:Irinotecan; D007659:Ketones / Q000494:pharmacology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D065856:Rubus / Q000737:chemistry; D027923:Sambucus / Q000737:chemistry; D053719:Tandem Mass Spectrometry; D029799:Vaccinium macrocarpon / Q000737:chemistry; D029800:Vaccinium myrtillus / Q000737:chemistry
chemical_list: D002074:Butanones; D007659:Ketones; D010936:Plant Extracts; D000077146:Irinotecan; C035522:raspberry ketone; D014453:Glucuronosyltransferase; D002166:Camptothecin
keywords: Herb-drug interaction; In vitro; Popularly-consumed berries; UGTs inhibition