Effects of Anthocyanins on Cytochrome P450 Enzymes and P-glycoprotein

花青素对细胞色素P450酶和P-糖蛋白的影响

• 批准号: 8196292
• 负责人: Michael John Hanley
• 金额: $ 3.75万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-15 至 2013-04-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8196292
• 关键词: Anthocyanidin; Anthocyanins; Anti-Inflammatory Agents; Anti-inflammatory; Antioxidants; Awareness; Back; Berry; Biological Factors; Blueberries; Buspirone; CYP2C9 gene; CYP3A4 gene; Caco-2 Cells; Calcium Channel Blockers; Clinical; Color; Consumption; Cytochrome P450; Data; Drug Interactions; Drug Kinetics; Drug Prescriptions; Ensure; Enterocytes; Enzymes; Family; Felodipine; Flavonoids; Fluconazole; Flurbiprofen; Food-Drug Interactions; Fruit; Gastrointestinal tract structure; Glycosides; Grapefruit juice; Health; Human; In Vitro; Individual; Inhibitory Concentration 50; Intestines; Investigation; Juice; Knowledge; Laboratories; Liver Microsomes; Malignant Neoplasms; Mediating; Metabolism; P-Glycoprotein; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Plasma; Play; Preparation; Property; Protein Isoforms; Pump; Reaction; Reporting; Risk; Role; Scientist; Source; System; Time; Water; Work; absorption; antimicrobial; clinically relevant; dietary constituent; fexofenadine; fruits and vegetables; hazard; in vitro activity; in vivo; indexing; inhibitor/antagonist; interest; member; monolayer; polyphenol; public health relevance

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.

描述（由申请人提供）：花色苷是许多浆果水果中发现的类黄酮，包括蓝莓。近年来，由于其报告的促进健康的特性，公众对蓝莓和其他含花青素的产品的兴趣增加了。反过来，很可能会出现含花色苷的产品和处方药的伴随食用。不幸的是，目前几乎没有关于与花青素有关的潜在药物相互作用风险的信息。该应用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AIM 1中，我们将确定花青素和花色苷在体外抑制CYP活性的潜力。在初步工作中，蓝莓汁以浓度抑制了CYP3A和CYP2C9的体外活性，而BBJ消耗后可以轻松地在胃肠道中实现。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，在该研究中，蓝莓汁将与探针底物（CYP3A）和Flurbiprofen（CYP2C9）共同融合。由于P-糖蛋白活性的改变也会影响药物处置，因此在AIM 3中，我们将检查花青素和花青素对P-糖蛋白介导的fexofenadine跨Caco-2细胞单层的转运的影响。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花青素的产品。 公共卫生相关性：本申请的结果将为科学家和临床医生提供有关药物相互作用的可能性的信息，当患者同时使用药物含有花青素的药物制剂时，就会出现毒品不足相互作用的可能性。