Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease with a global prevalence of 25%. However, the medicines approved by the FDA or EMA are still not commercially available for the treatment of NAFLD. The NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome plays a crucial role in inflammatory responses, and the mechanisms related to steatohepatitis have been sufficiently clarified. NLRP3 has been widely evaluated as a potential target for multiple active agents in treating NAFLD. As a quercetin glycoside, isoquercitrin (IQ) has a broad inhibitory effect on oxidative stress, cancers, cardiovascular diseases, diabetes, and allergic reactions in vitro and in vivo. This study aimed to investigate the undercover mechanism of IQ in the treatment of NAFLD, particularly in anti-steatohepatitis, by suppressing the NLRP3 inflammasome. In this study, a methionine-choline-deficient induced steatohepatitis mice model was used to explore the effect of IQ on NAFLD treatment. Further mechanism exploration based on transcriptomics and molecular biology revealed that IQ inhibited the activated NLRP3 inflammasome by down-regulating the expression of heat shock protein 90 (HSP90) and suppressor of G-two allele of Skp1 (SGT1). In conclusion, IQ could alleviate NAFLD by inhibiting the activated NLRP3 inflammasome by suppressing the expression of HSP90.

Cichorium glandulosum Boiss. et Huet (CG) and Cichorium intybus L. (CI) are widely used as the main raw material of functional food with hepatoprotective and hypoglycemic effects. Due to the lack of comparison on the chemical ingredients and efficacy, they were often used imprecisely and interchangeably. It is necessary to distinguish between them. With the plant metabolomics based on high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC-QTOF-MS) and multivariate chemometric techniques, the chemical ingredients were characterized and 59 compounds between CG and CI were classified. As for antioxidative and hypoglycemic activities in vitro, CI extraction exhibited better antioxidant activity than CG, while CG extraction showed stronger hypoglycemic activity. Furthermore, a bivariate correlation between the chemical composition and efficacy of the extract was also analyzed, and three differentially strong correlation components between CI and CG were prepared, and the antioxidative and hypoglycemic efficacies were compared in vivo and different active phenotypes were obtained. Finally, we revealed chemical and biological differences between CG and CI, providing a basis for achieving better quality control and developing more effective functional foods.