de Ferrars R M, Czank C, Zhang Q, Botting N P, Kroon P A, Cassidy A, Kay C D
Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich, UK.
Br J Pharmacol. 2014 Jul;171(13):3268-82. doi: 10.1111/bph.12676.
Anthocyanins are phytochemicals with reported vasoactive bioactivity. However, given their instability at neutral pH, they are presumed to undergo significant degradation and subsequent biotransformation. The aim of the present study was to establish the pharmacokinetics of the metabolites of cyanidin-3-glucoside (C3G), a widely consumed dietary phytochemical with potential cardioprotective properties.
A 500 mg oral bolus dose of 6,8,10,3',5'-(13)C5-C3G was fed to eight healthy male participants, followed by a 48 h collection (0, 0.5, 1, 2, 4, 6, 24, 48 h) of blood, urine and faecal samples. Samples were analysed by HPLC-ESI-MS/MS with elimination kinetics established using non-compartmental pharmacokinetic modelling.
Seventeen (13)C-labelled compounds were identified in the serum, including (13)C5-C3G, its degradation products, protocatechuic acid (PCA) and phloroglucinaldehyde (PGA), 13 metabolites of PCA and 1 metabolite derived from PGA. The maximal concentrations of the phenolic metabolites (Cmax ) ranged from 10 to 2000 nM, between 2 and 30 h (tmax) post-consumption, with half-lives of elimination observed between 0.5 and 96 h. The major phenolic metabolites identified were hippuric acid and ferulic acid, which peaked in the serum at approximately 16 and 8 h respectively.
Anthocyanins are metabolized to a structurally diverse range of metabolites that exhibit dynamic kinetic profiles. Understanding the elimination kinetics of these metabolites is key to the design of future studies examining their utility in dietary interventions or as therapeutics for disease risk reduction.
花色苷是一类具有血管活性生物活性报道的植物化学物质。然而，鉴于它们在中性pH值下的不稳定性，推测它们会发生显著降解及随后的生物转化。本研究的目的是确定花青素-3-葡萄糖苷（C3G）代谢产物的药代动力学，C3G是一种广泛食用的具有潜在心脏保护特性的膳食植物化学物质。
给8名健康男性参与者口服500 mg的6,8,10,3',5'-(13)C5-C3G单次大剂量给药，随后在48小时内（0、0.5、1、2、4、6、24、48小时）收集血液、尿液和粪便样本。使用非房室药代动力学模型建立消除动力学，通过HPLC-ESI-MS/MS分析样本。
在血清中鉴定出17种(13)C标记的化合物，包括(13)C5-C3G、其降解产物原儿茶酸（PCA）和间苯三酚醛（PGA）、PCA的13种代谢产物以及1种源自PGA的代谢产物。酚类代谢产物的最大浓度（Cmax）在食用后2至30小时（tmax）之间为10至2000 nM，消除半衰期在0.5至96小时之间。鉴定出的主要酚类代谢产物是马尿酸和阿魏酸，它们在血清中的峰值分别约为16小时和8小时。
花色苷被代谢为结构多样的一系列代谢产物，这些代谢产物呈现出动态的动力学特征。了解这些代谢产物的消除动力学是未来研究其在膳食干预中的效用或作为降低疾病风险治疗方法的关键。
