Effects of Anthocyanins on Cytochrome P450 Enzymes and P-glycoprotein

描述(申请人提供)：花青素是一种类黄酮类化合物，存在于许多浆果类水果中，包括蓝莓。近年来，由于蓝莓和其他含有花青素的产品被报道具有促进健康的特性，公众对它们的兴趣有所增加。反过来，含有花青素的产品很可能与处方药一起消费。不幸的是，目前关于与花青素相关的潜在药物相互作用风险的信息很少。本应用的目的是确定花色苷对细胞色素P450(CYP)酶和药物转运蛋白P-糖蛋白的影响。在目标1中，我们将确定花色苷和花青素在体外抑制CYP活性的可能性。在前期工作中，蓝莓汁在摄入BBJ后很容易在胃肠道达到的浓度，可以抑制CYP3A和CYP2C9的体外活性。因此，在目标2中，我们将通过进行药代动力学研究来确定这些体外相互作用的临床相关性，在该研究中，蓝莓汁将与探针底物丁螺环酮(CYP3A)和氟比洛芬(CYP2C9)共同给药。由于P-糖蛋白活性的改变也可以影响药物的处置，在目标3中，我们将检测花青素和花青素对P-糖蛋白介导的非索非那定跨Caco-2细胞单层转运的影响。综上所述，从这些研究中获得的知识将有助于确保公众安全使用含有花青素的产品。 公共卫生相关性：这项应用的结果将为科学家和临床医生提供信息，说明当患者同时服用含有花青素的制剂时，药物与营养之间可能发生的相互作用。

DESCRIPTION (provided by applicant): Anthocyanins are a class of flavonoids found in many berry fruits, including blueberries. Public interest in blueberries and other anthocyanin-containing products has increased in recent years due to their reported health-promoting properties. In turn, the concomitant consumption of anthocyanin-containing products with prescription drugs is likely to occur. Unfortunately, little information is currently available regarding the potential drug interaction risks associated with anthocyanins. The objective of this application is to establish the effects of anthocyanins on the cytochrome P450 (CYP) enzymes and the drug transporter, P-glycoprotein. In Aim 1, we will determine the potential of anthocyanins and anthocyanidins to inhibit CYP activity in vitro. In preliminary work, blueberry juice inhibited the in vitro activity of CYP3A and CYP2C9 at concentrations that could easily be achieved in the gastrointestinal tract after BBJ consumption. Consequently, in Aim 2, we will ascertain the clinical relevance of these in vitro interactions by conducting pharmacokinetic studies in which blueberry juice will be coadministered with the probe substrates buspirone (CYP3A) and flurbiprofen (CYP2C9). Since alterations in the activity of P-glycoprotein can also influence drug disposition, in Aim 3 we will examine the effects of anthocyanins and anthocyanidins on P-glycoprotein-mediated fexofenadine transport across Caco-2 cell monolayers. Taken together, the knowledge gained from these studies will help ensure the safe use of anthocyanin-containing products by the public. PUBLIC HEALTH RELEVANCE: The results of this application will provide information for scientists and clinicians regarding the potential for drug-nutrient interactions to occur when patients concomitantly consume anthocyanin-containing preparations with their medications.