Nonalcoholic fatty liver disease (
NAFLD) is one of the most common
liver diseases which lacks ideal treatment options.
Kaempferol and
kaempferide, two natural
flavonol compounds isolated from Hippophae rhamnoides L., were reported to exhibit a strong regulatory effect on lipid metabolism, for which the mechanism is largely unknown. In the present study, we investigated the effects of
kaempferol and
kaempferide on
oleic acid (OA)-treated HepG2 cells, a widely used in vitro model of
NAFLD. The results indicated an increased accumulation of lipid droplets and
triacylglycerol (TG) by OA, which was attenuated by
kaempferol and
kaempferide (5, 10 and 20 μM). Western blot analysis demonstrated that
kaempferol and
kaempferide reduced expression of lipogenesis-related
proteins, including
sterol regulatory element-binding protein 1 (SREBP1),
fatty acid synthase (FAS) and
stearoyl-CoA desaturase 1 (SCD-1). Expression of
peroxisome proliferator-activated receptor γ (PPARγ) and
CCAAT enhancer binding proteins β (C/EBPβ), two adipogenic
transcription factors, was also decreased by
kaempferol and
kaempferide treatment. In addition, western blot analysis also demonstrated that
kaempferol and
kaempferide reduced expression of
heme oxygenase-1 (HO-1) and nuclear
transcription factor-erythroid 2-related factor 2 (Nrf2). Molecular docking was performed to identify the direct molecular targets of
kaempferol and
kaempferide, and their binding to SCD-1, a critical regulator in lipid metabolism, was revealed. Taken together, our findings demonstrate that
kaempferol and
kaempferide could attenuate OA-induced
lipid accumulation and oxidative stress in HepG2 cells, which might benefit the treatment of
NAFLD.