Organs‐on‐chip (OoCs) are catching on as a promising and valuable alternative to animal models, in line with the 3Rs initiative. OoCs enable the creation of three‐dimensional (3D) tissue microenvironments with physiological and pathological relevance at unparalleled precision and complexity, offering new opportunities to model human diseases and to test the potential therapeutic effect of drugs, while overcoming the limited predictive accuracy of conventional 2D culture systems. Here, we present a liver‐on‐a‐chip model to investigate the effects of two naturally occurring polyphenols, namely quercetin and hydroxytyrosol, on nonalcoholic fatty liver disease (NAFLD) using a high‐content analysis readout methodology. NAFLD is currently the most common form of chronic liver disease; however, its complex pathogenesis is still far from being elucidated, and no definitive treatment has been established so far. In our experiments, we observed that both polyphenols seem to restrain the progression of the free fatty acid‐induced hepatocellular steatosis, showing a cytoprotective effect due to their antioxidant and lipid‐lowering properties. In conclusion, the findings of the present work could guide novel strategies to contrast the onset and progression of NAFLD.

中文翻译：

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槲皮素和羟基酪醇作为肝脏脂肪变性的调节剂：NAFLD 芯片研究。

与 3R 倡议相一致，片上器官 (OoC) 作为一种有前途且有价值的动物模型替代品正在流行起来。OoC 能够以无与伦比的精度和复杂性创建具有生理和病理相关性的三维 (3D) 组织微环境，为模拟人类疾病和测试药物的潜在治疗效果提供了新的机会，同时克服了传统 2D 的有限预测准确性文化系统。在这里，我们提出了一个肝脏芯片模型，使用高内涵分析读出方法研究两种天然存在的多酚，即槲皮素和羟基酪醇，对非酒精性脂肪性肝病 (NAFLD) 的影响。NAFLD 是目前最常见的慢性肝病。然而，其复杂的发病机制仍远未阐明，并且目前还没有确定的治疗方法。在我们的实验中，我们观察到这两种多酚似乎都能抑制游离脂肪酸诱导的肝细胞脂肪变性的进展，由于它们的抗氧化和降脂特性，显示出细胞保护作用。总之，目前工作的发现可以指导新的策略来对比 NAFLD 的发病和进展。