Novel insights into the role of quercetin and kaempferol from Carthamus tinctorius L. in the management of nonalcoholic fatty liver disease via NR1H4-mediated pathways.

This study investigates the novel therapeutic potential of quercetin and kaempferol, two bioactive compounds derived from Carthamus tinctorius L., in treating nonalcoholic fatty liver disease (NAFLD) by modulating the bile acid receptor NR1H4 (Nuclear Receptor Subfamily 1 Group H Member 4) and its associated metabolic pathways. A rat model of NAFLD was established, and RNA sequencing and proteomics were carefully employed to identify differential gene expressions associated with the disease. The active components of Carthamus tinctorius L. were screened, followed by the construction of a comprehensive network that maps the interactions between these components, NR1H4 and NAFLD-related pathways. Both in vitro (using HepG2 cells) and in vivo experiments were conducted to evaluate the effects on NR1H4 expression levels through Western blot and RT-qPCR analyses. Our findings identify NR1H4 as a pivotal target in NAFLD. Network pharmacology analysis indicates that quercetin and kaempferol play crucial roles in combating NAFLD, with in vitro and in vivo experiments confirming their ability to mitigate hepatocyte steatosis by enhancing NR1H4 expression. Notably, the protective effects of these compounds were inhibited by the NR1H4 antagonist guggulsterone, highlighting the importance of NR1H4 upregulation. This study demonstrates the novel therapeutic efficacy of quercetin and kaempferol from Carthamus tinctorius L. in treating NAFLD through NR1H4 upregulation. This mechanism contributes to the regulation of lipid metabolism, improvement of liver function, reduction of inflammation, and alleviation of oxidative stress, offering a promising direction for future NAFLD treatment strategies.