Ginseng root extract alleviates nonalcoholic fatty liver disease by modulating mitochondrial function and regulating lipid metabolism via the AMPK pathway.

BACKGROUND

Nonalcoholic fatty liver disease (NAFLD) is closely associated with abnormal lipid metabolism and insulin resistance, and its prevalence is rapidly increasing. Furthermore, mitochondrial dysfunction plays an essential role in NAFLD development, thereby highlighting the urgent need for novel therapeutic strategies that target the mitochondrial.

PURPOSE: To clarify the protective effects of ginseng root extract (GRE) on free fatty acid (FFA)-induced NAFLD in human hepatoblastoma (HepG2) cells and explore its potential mechanism for improving NAFLD through mitochondrial function.

METHODS

An FFA-induced NAFLD cell model was established in HepG2 cells, and cells were subsequently treated with GRE. Thereafter, hepatic lipid accumulation, reactive oxygen species (ROS) levels, mitochondrial function and injury, apoptosis, and the cell cycle were monitored. The expression of adenosine monophosphate-activated protein kinase (AMPK) and its downstream targets were also analyzed. Moreover, an AMPK inhibitor was used to validate the AMPK-mediated regulation of lipid metabolism and mitochondrial function improvement.

RESULTS

GRE markedly inhibited lipid accumulation, reduced ROS generation, and improved mitochondrial function. Moreover, GRE promoted AMPK phosphorylation and suppressed the expression of sterol regulatory element binding protein 1c, fatty acid synthase, and peroxisome proliferator-activated receptor γ expression, thereby inhibiting fatty acid synthesis and enhancing fatty acid catabolism. Furthermore, GRE alleviated mitochondrial dysfunction by reducing mitochondrial oxidative stress, mitochondrial lipid peroxidation, and membrane transition pore permeability, and reduced FFA-induced apoptosis and cell cycle abnormalities by activating the AMPK signaling pathway.

CONCLUSIONS

GRE shows promising potential as a natural treatment option for NAFLD.