Effects of Anthocyanins on Cytochrome P450 Enzymes and P-glycoprotein

描述（由申请人提供）：花青素是一类类黄酮，存在于许多浆果类水果中，包括蓝莓。近年来，公众对蓝莓和其他含有花青素的产品的兴趣有所增加，因为它们被报道具有促进健康的特性。反过来，含有花青素的产品与处方药的同时消费很可能发生。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。本应用程序的目的是建立花青素对细胞色素P450 （CYP）酶和药物转运蛋白p -糖蛋白的影响。在目的1中，我们将确定花青素和花青素在体外抑制CYP活性的潜力。在前期研究中，蓝莓汁对体外CYP3A和CYP2C9活性的抑制作用达到了饮用BBJ后胃肠道中容易达到的浓度。因此，在Aim 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，其中蓝莓汁将与探针底物丁螺环酮（CYP3A）和氟比洛芬（CYP2C9）共同施用。由于p糖蛋白活性的改变也会影响药物处置，在Aim 3中，我们将研究花青素和花青素对p糖蛋白介导的非索非那定跨Caco-2细胞单层转运的影响。总的来说，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。

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.