Scutellaria baicalensis has been reported to improve the lipid metabolism of high-fat diet-induced
liver dysfunction, but direct evidence is rare. This study aimed to explore the effects and mechanisms of S. baicalensis and its major constituent
baicalin on hepatic lipotoxicity. KK-Ay mice and
orotic acid (OA)-induced
nonalcoholic fatty liver disease (
NAFLD) rats were used to evaluate lipid metabolism regulatory effects.
Sodium oleate-induced
triglyceride-accumulated HepG2 cells were used for the mechanism study, pretreated with or without compound C or
STO-609 or transfected with liver
kinase B1 (LKB1)
siRNA. In KK-Ay mice, S. baicalensis extract showed a decreased effect on serum and hepatic
triglycerides, total cholesterols, and
free fatty acid (FFA) levels after 8 weeks of treatment. In OA-induced
NAFLD rats, 18 days of treatment with
baicalin significantly inhibited hepatic
lipid accumulation, attenuating hepatocyte
hypertrophy, vacuolization and
necrosis. S. baicalensis and
baicalin treatment significantly suppressed the
sterol regulatory
element binding protein-1c (SREBP-1c) transcriptional program with downregulation of gene and
protein expression of
SREBP-1c (both precursor and mature fraction) and
acetyl-CoA carboxylase,
fatty acid synthase and
stearoyl-CoA desaturase, and upregulation of
AMP-activated protein kinase (AMPK),
carnitine palmitoyl
transferase 1 and
nuclear respiratory factor 2 in the liver. Furthermore, activation of AMPK by
baicalin was observed to be relative to the increase in phosphorylation of
calmodulin-dependent protein kinase kinase. Taken together, S. baicalensis conferred preventive effects against FFA-induced lipotoxicity through the AMPK-mediated SREBP signaling pathway.