OBJECTIVE@#Cassiae
Semen (CS, Juemingzi in
Chinese) has been used for thousands of years in ancient
Chinese history for relieving
constipation, improving
liver function as well as preventing
myopia. Here we aimed to elucidate the anti-steatosis effect and underlying mechanism of CS against
non-alcoholic fatty liver disease (
NAFLD).@*
METHODS@#
High-performance liquid chromatography (
HPLC) was used to identify the major components of CS
water extract.
Mice were fed with a high-fat and
sugar-
water (HFSW)
diet to induce hepatic steatosis and then treated with CS. The anti-
NAFLD effect was determined by measuring
serum biomarkers and histopathology
staining. Additionally, the effects of CS on
cell viability and
lipid metabolism in
oleic acid and
palmitic acid (OAPA)-treated
HepG2 cells were measured. The expression of
essential genes and
proteins involved in
lipid metabolism and
autophagy signalings were measured to uncover the underlying mechanism.@*RESULTS@#Five compounds, including aurantio-obtusin, rubrofusarin gentiobioside, cassiaside C,
emodin and rhein were simultaneously identified in CS extract. CS not only improved the
diet-induced hepatic steatosis in vivo, as indicated by decreased number and size of
lipid droplets, hepatic and
serum triglycerides (TG) levels, but also markedly attenuated the OAPA-induced
lipid accumulation in
hepatocytes. These
lipid-lowering effects induced by CS were largely dependent on the inhibition of
fatty acid synthase (FASN) and the activation of
autophagy-related signaling, including
AMP-activated protein kinase (AMPK),
light chain 3-II (LC3-II)/ LC3-1 and
autophagy-related gene5 (ATG5).@*CONCLUSION@#Our study suggested that CS effectively protected
liver steatosis via decreasing FASN-related
fatty acid synthesis and activating AMPK-mediated
autophagy, which might become a promising
therapeutic strategy for relieving
NAFLD.