Cichoric acid (CA), a polyphenol component from Echinacea purpurea, exhibits preventive effects on liver lipid-metabolism disorders in obesity. This research aimed to determine the role of circadian rhythm signaling during the process of CA-attenuated lipid accumulation in hepatocytes. In the current study, CA treatments improved cell morphology changes and hepatic lipid levels, which were triggered by free fatty acids (2:1, oleate: palmitate) in a dose-dependent way. Besides, CA (200 μM) regulated the circadian rhythm expressions of clock genes and the relatively shallow daily oscillations. Moreover, silencing Bmal1 significantly blocked the p-Akt/Akt pathway to 80.1% ± 1.5% and the p-GSK3β/GSK3β pathway to 64.7% ± 2.8% ( p < 0.05). Furthermore, silencing Bmal1 elevated the expressions of FAS and ACC to 122.4% ± 5.6% and 114.9% ± 1.7% in protein levels ( p < 0.05) and to 166.5% ± 18.5% and 131.4% ± 5.5% in mRNA levels ( p < 0.05). Therefore, our results demonstrated that CA has a Bmal1 resistance to lipid accumulation by enhancing the Akt/GSK3β signaling pathways and modulating the downstream expressions related to lipid metabolism, which indicated that CA might be useful as a natural and promising nonalcoholic fatty liver diseases (NAFLD) modulator.
Keywords: BMAL1; cichoric acid; circadian rhythm; lipid metabolism; nonalcoholic fatty liver disease.