Natural polyphenols Quercetin and Hydroxytyrosol as effective inhibitors of hepatic steatosis: a NAFLD-on-a-chip study

Organs-on-chip (OoCs) are catching on as a promising and valuable alternative to animal models, in line with the 3Rs principle. OoCs enable the creation of 3D tissue microenvironments with pathophysiological relevance at unparalleled precision and complexity, offering new opportunities to model human diseases in vitro and to test the potential therapeutic effect of novel drugs, while overcoming the limited predictive accuracy of conventional 2D culture systems (1,2,3). Here, we present a liver-on-a-chip platform to investigate the effects of two plant-derived polyphenols, namely Quercetin and Hydroxytyrosol, on nonalcoholic fatty liver disease (NAFLD) using a high-content analysis readout methodology (4,5). NAFLD is currently the most common cause of chronic liver disease worldwide; however, its complex and multifactorial pathogenesis is still far from being clear, and a definitive treatment has not yet been established (6,7). In our experiments, we observed that both polyphenols seem to hamper the progression of the free fatty acid-induced hepatocellular steatosis, showing a cytoprotective effect due to their antioxidant and lipid-lowering properties (8). In conclusion, the findings of the present work could provi