Curcumin (CUR) is a major component of turmeric Curcuma longa, which is often used in food or as a dietary supplement. The purpose of this preclinical study is to investigate the acute pharmacokinetic and pharmacodynamic (PK/PD) profiles of two commercially marketed CUR products (GNC and Vitamin Shoppe) and a CUR powder from Sigma in female rats. Plasma samples were collected at specific time points and analyzed for CUR and its metabolite curcumin-O-glucuronide. RNA was extracted from leukocytes and analyzed for the expression of Nrf2-mediated antioxidant genes Nrf2, Ho-1, and Nqo1 by qPCR as selected PD markers. CUR PK was characterized by a 2-compartment model (2CM) after intravenous (IV) or oral administrations. Compared to IV CUR, the absolute bioavailability (F) of CUR for GNC (GC) is 0.9%, Vitamin Shoppe (VC) is 0.6% and Sigma (SC) is 3.1%. Pharmacodynamically, all three formulations showed induction of antioxidant Nrf2, Ho-1 and Nqo1 gene expression in rat leucocytes. PK/PD modeling of CUR’s effect on antioxidant gene expression was well captured by an indirect response model. Physiologically based PK modeling and simulation using GastroPlus described the observed PK data reasonably well. In summary, our current study shows that the absolute oral bioavailability of the parent CUR was very low for all three formulations. However, despite the low CUR plasma concentrations, all three oral CUR formulations displayed PD response in the induction of Nrf2-mediated antioxidant genes, suggesting the potential of oral CUR contributing to the overall health beneficial effects of oral CUR.

中文翻译：

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三种姜黄素口服制剂在大鼠中的药代动力学和药效学。

姜黄素（CUR）是姜黄姜黄的主要成分，常用于食品或膳食补充剂中。这项临床前研究的目的是研究两种市售CUR产品（GNC和Vitamin Shoppe）以及Sigma的CUR粉末在雌性大鼠中的急性药代动力学和药效学（PK / PD）特性。在特定时间点收集血浆样品，并分析CUR及其代谢物姜黄素-O-葡糖苷酸。从白细胞中提取RNA，并通过qPCR分析Nrf2介导的抗氧化基因Nrf2，Ho-1和Nqo1的表达，作为选定的PD标记。静脉（IV）或口服给药后，CUR PK的特征是2室模型（2CM）。与IV CUR相比，GNC（GC）的CUR绝对生物利用度（F）为0.9％，Vitamin Shoppe（VC）为0.6％，Sigma（SC）为3.1％。在药理学上，所有三种制剂均在大鼠白细胞中显示出抗氧化剂Nrf2，Ho-1和Nqo1基因的表达。通过间接反应模型可以很好地捕获CUR对抗氧化剂基因表达的作用的PK / PD模型。使用GastroPlus进行的基于生理的PK建模和仿真合理地描述了观察到的PK数据。综上所述，我们目前的研究表明，对于所有三种制剂，母体CUR的绝对口服生物利用度都非常低。然而，尽管CUR血浆浓度低，但所有三种口服CUR制剂在诱导Nrf2介导的抗氧化剂基因中均显示出PD反应，表明口服CUR的潜力有助于口服CUR的整体健康益处。