Metabolomic analysis has been used to characterize the effects and mechanisms of drugs for
nonalcoholic fatty liver disease (
NAFLD) at the metabolic level.
Nuciferine is an active component derived from folium nelumbinis and has been demonstrated to have beneficial effects on a high-fat diet (HFD) induced hepatic steatosis model. However, the effect of the altered metabolites of
nuciferine on
NAFLD has not yet been elucidated. In this study, we established a
NAFLD rat model using HFD and treated with
nuciferine. The
lipid content levels, pro-inflammatory
cytokines, and oxidative stress were investigated to access the
therapeutic effects of
nuciferine. Additionally, the metabolic regulatory mechanisms of
nuciferine on
NAFLD were analyzed using untargeted metabolomics. Gene expression of the key
enzymes related to the changed metabolic pathways following
nuciferine intervention was also investigated. The results showed that
nuciferine treatment significantly reduced the
body weight, levels of
lipids, and liver
enzymes in the blood and improved the hepatic steatosis in the
NAFLD rat model.
Nuciferine treatment also increased the activities of
superoxide dismutase (SOD) and
glutathione peroxidase (GSH-Px) and decreased the levels of methane dicarboxylic
aldehyde (MDA) in the liver.
Nuciferine treatment decreased the serum levels of
interleukin (IL)-6, IL-1β, and
tumor necrosis factor-alpha (TNF-α) and upregulated the gene expression of
IL-6, IL-1β, and TNF-α in the liver. Metabolomic analysis indicated a metabolism disorder in the
NAFLD rat model reflected in a dysfunction of the
glycerophospholipid,
linoleic acid,
alpha-linolenic acid,
arginine and
proline metabolism. Conversely, treatment with
nuciferine improved the metabolic disorder in the
NAFLD rat model.
Nuciferine treatment also regulated the gene expression of key
enzymes related to the
glycerophospholipid,
linoleic acid, and
alpha-linolenic acid metabolism pathways in the liver. In conclusion, our study demonstrated an amelioration of the metabolic disorders following
nuciferine treatment in
NAFLD rat model. Our study contributes to the understanding of the effects and mechanisms of drugs for complex diseases using metabolomic analysis and experimental approaches.