The citrus fruit-derived flavanone glycoside narirutin is a novel potent inhibitor of organic anion-transporting polypeptides
The citrus fruit-derived flavanone glycoside narirutin is a novel potent inhibitor of organic anion-transporting polypeptides
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柑橘类水果衍生的黄烷酮糖苷 narirutin 是一种新型的有机阴离子转运多肽的有效抑制剂
DOI：
10.1021/acs.jafc.0c06132
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Ohtani H.
中科院分区：
文献类型：
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作者：
Morita T;Akiyoshi T;Sato R;Uekusa Y;Katayama K;Yajima K;Imaoka A;Sugimoto Y;Kiuchi F;Ohtani H.
有机阴离子转运多肽（OATP）1A 2和OATP 2B 1在小肠中表达，并参与药物吸收。我们确定了葡萄柚汁中存在的naririraline是一种新型的OATP抑制剂。柑橘类水果jabara也含有高水平的nariririrabine;因此，我们研究了jabara果汁对OATP的抑制效力。使用表达OATP的HEK 293细胞评价了各种相关化合物对OATP转运活性的抑制作用。纳瑞鲁肽对OATP 1A 2和OATP 2B 1介导转运的IC 50值分别为22.6和18.2 μM。葡萄柚汁中的其他黄烷酮衍生物也抑制OATP 1A 2/OATP 2B 1介导的转运（抑制效力顺序：柚皮素>柚皮苷>柚皮苷）。5% jabara果汁显著抑制OATP 1A 2和OATP 2B 1介导的转运，分别为67 ± 11和81 ± 5.5%（p< 0.05）。基于葡萄柚汁中OATP的抑制效力和水平，葡萄柚汁对OATP的抑制可归因于柚皮苷和柚皮苷。含有柚皮苷的柑橘× jabara有效抑制OATP介导的转运。
Organic anion-transporting polypeptides (OATPs) 1A2 and OATP2B1 are expressed in the small intestine and are involved in drug absorption. We identified narirutin, which is present in grapefruit juice, as a novel OATP inhibitor. The citrus fruit jabara also contains high levels of narirutin; therefore, we investigated the inhibitory potency of jabara juice against OATPs. The inhibitory effects of various related compounds on the transport activity of OATPs were evaluated using OATP-expressing HEK293 cells. The IC50values of narirutin for OATP1A2- and OATP2B1-mediated transport were 22.6 and 18.2 μM, respectively. Other flavanone derivatives from grapefruit juice also inhibited OATP1A2/OATP2B1-mediated transport (order of inhibitory potency: naringenin > narirutin > naringin). Five percent jabara juice significantly inhibited OATP1A2- and OATP2B1-mediated transport by 67 ± 11 and 81 ± 5.5%, respectively (p< 0.05). Based on their inhibitory potency and levels in grapefruit juice, the inhibition of OATPs by grapefruit juice is attributable to both naringin and narirutin.Citrus × jabara, which contains narirutin, potently inhibits OATP-mediated transport.