Brunetti Luigi, Wang Lujing, Wassef Andrew, Gong Yongjia, Brinker Anita, Buckley Brian, Lipsky Peter E, Ondar Patricia, Poiani George, Zhao Liping, Kong Ah-Ng, Schlesinger Naomi
Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ, 08854, USA.
Robert Wood Johnson University Hospital Somerset, Somerville, NJ, 08876, USA.
Mol Nutr Food Res. 2023 May;67(9):e2200550. doi: 10.1002/mnfr.202200550. Epub 2023 Mar 12.
Tart cherries (TCs) contain high levels of anthocyanins that exert potent antioxidant and antiinflammatory effects and potentially benefit individuals with gout.
This study aims to quantitate the major anthocyanins in TC Juice Concentrate (TCJC) and identify the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of the major anthocyanin cyanidin-3-glucosylrutinoside (C3GR). A PK-PD study enrolling human subjects with a history of gout is performed. Subjects are randomized to receive either 60 or 120 mL of TCJC. Anthocyanins are quantitated using liquid chromatography-mass spectroscopy (LCMS). Antioxidant and antiinflammatory mRNA expression is measured using real-time qPCR before and after the administration of TCJC. A population PK model (popPK) is fit to the experimental data, and an indirect PD model (IDR) is constructed in Monolix.
Of the bioavailable anthocyanins, C3GR achieves the highest plasma concentration in a dose-dependent manner. A popPK predicts anthocyanin exposure, and an IDR produces reasonable approximations of PD effects.
酸樱桃（TC）含有高水平的花青素，具有强大的抗氧化和抗炎作用，可能对痛风患者有益。
本研究旨在定量浓缩酸樱桃汁（TCJC）中的主要花青素，并确定主要花青素矢车菊素 - 3 - 葡萄糖基芸香糖苷（C3GR）的药代动力学（PK）和药效学（PD）参数。进行了一项针对有痛风病史的人类受试者的PK - PD研究。受试者被随机分配接受60或120 mL的TCJC。使用液相色谱 - 质谱联用（LCMS）对花青素进行定量。在给予TCJC之前和之后，使用实时定量PCR测量抗氧化和抗炎mRNA表达。将群体药代动力学模型（popPK）拟合到实验数据，并在Monolix中构建间接药效学模型（IDR）。
在可生物利用的花青素中，C3GR以剂量依赖性方式达到最高血浆浓度。popPK预测花青素暴露，IDR产生合理的药效学效应近似值。
