PDF(Pubmed)
Abstract：
Aloe-emodin, a natural hydroxyanthraquinone, exerts both adverse and protective effects. This study aimed at investigating these potential effects of aloe-emodin in humans upon the use of food supplements and herbal medicines using a physiologically based kinetic (PBK) modeling-facilitated quantitative in vitro to in vivo extrapolation (QIVIVE) approach. For this, PBK models in rats and humans were established for aloe-emodin including its active metabolite rhein and used to convert in vitro data on hepatotoxicity, nephrotoxicity, reactive oxidative species (ROS) generation, and Nrf2 induction to corresponding in vivo dose-response curves, from which points of departure (PODs) were derived by BMD analysis. The derived PODs were subsequently compared to the estimated daily intakes (EDIs) resulting from the use of food supplements or herbal medicines. It is concluded that the dose levels of aloe-emodin from food supplements or herbal medicines are unlikely to induce toxicity, ROS generation, or Nrf2 activation in liver and kidney.
摘要：
芦荟大黄素,一种天然的羟基蒽醌,同时发挥不利和保护作用。这项研究旨在使用基于生理的动力学（PBK）建模促进的定量体外到体内外推（QIVIVIVE）方法，研究芦荟大黄素在使用食品补充剂和草药时对人类的这些潜在影响。为此，在大鼠和人的PBK模型中建立了芦荟大黄素，包括其活性代谢产物大黄酸，并用于转换肝毒性的体外数据。肾毒性，反应性氧化物质（ROS）的产生，和Nrf2诱导到相应的体内剂量反应曲线，通过BMD分析得出出发点(POD)。随后将得出的POD与使用食品补充剂或草药产生的估计每日摄入量（EDI）进行比较。结论是，来自食品补充剂或草药的芦荟大黄素的剂量水平不太可能引起毒性，ROS生成，或Nrf2在肝脏和肾脏激活。
