Effect of pterostilbene on in vitro drug metabolizing enzyme activity
Effect of pterostilbene on in vitro drug metabolizing enzyme activity
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DOI：
10.1016/j.jsps.2019.01.001
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发表时间：
2019-03-01
影响因子：
4.1
通讯作者：
Frye, Reginald F.
中科院分区：
文献类型：
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作者：
Albassam, Ahmed A.;Frye, Reginald F.
紫檀芪是一种天然多酚化合物，存在于小浆果中，与白藜芦醇有关，但具有更好的生物利用度和更长的半衰期。本研究的目的是评估紫檀芪对体外药物代谢的潜在抑制作用。以酶选择性底物阿莫地喹（CYP 2C 8）、咪达唑仑（CYP 3A 4）、雌二醇（UGT 1A 1）、5-羟色胺（UGT 1A 6）和麦考酚酸（UGT 1A 8/9/10）为底物，研究了紫檀芪对细胞色素P450（CYP）和尿苷二磷酸葡萄糖醛酸转移酶（UGT）活性的影响。IC 50值用于表示抑制强度。此外，使用体积/剂量指数（AUC）估计体内相互作用的可能性。紫檀芪显著抑制CYP 2C 8和UGT 1A 6活性。CYP 2C 8和UGT 1A 6抑制的IC 50（平均值+/- SE）值分别为3.0 +/- 0.4 μ M和15.1 +/- 2.8 μ M; CYP 2C 8和UGT 1A 6的AUC均超过预定阈值5 L/剂，表明存在体内相互作用的可能性。紫檀芪不抑制其他酶选择性底物的代谢。这项研究的结果表明，紫檀芪抑制CYP 2C 8和UTG 1A 6活性在体外，并可能抑制这些酶在体内的代谢。需要进行临床研究来评价这些相互作用的体内相关性。(C)2019年，任作家。Elsevier B. V.代表沙特国王大学制作和主持。
Pterostilbene is a natural polyphenol compound found in small berries that is related to resveratrol, but has better bioavailability and a longer half-life. The purpose of this study was to assess the potential inhibitory effect of pterostilbene on in vitro drug metabolism. The effect of pterostilbene on cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) enzyme activities were studied using the enzyme-selective substrates amodiaquine (CYP2C8), midazolam (CYP3A4), estradiol (UGT1A1), serotonin (UGT1A6) and mycophenolic acid (UGT1A8/9/10). The IC50 value was used to express the strength of inhibition. Further, a volume per dose index (VDI) was used to estimate the potential for in vivo interactions. Pterostilbene significantly inhibited CYP2C8 and UGT1A6 activities. The IC50 (mean +/- SE) values for CYP2C8 and UGT1A6 inhibition were 3.0 +/- 0.4 mu M and 15.1 +/- 2.8 mu M, respectively; the VDI exceeded the predefined threshold of 5 L/dose for both CYP2C8 and UGT1A6, suggesting a potential for interaction in vivo. Pterostilbene did not inhibit the metabolism of the other enzyme-selective substrates. The results of this study indicate that pterostilbene inhibits CYP2C8 and UTG1A6 activity in vitro and may inhibit metabolism by these enzymes in vivo. Clinical studies are warranted to evaluate the in vivo relevance of these interactions. (C) 2019 The Authors. Production and hosting by Elsevier B.V. on behalf of King Saud University.