Nonalcoholic fatty liver disease (
NAFLD) is becoming one of the most common chronic
liver diseases in the world. One of the features of
NAFLD is hepatic fat accumulation, which further causes hepatic steatosis,
fibrosis, and
inflammation.
Saponins, the major pharmacologically active ingredients isolated from Panax notoginseng, contain several
ginsenosides, which have various pharmacological and therapeutic functions. However, the
ginsenoside-specific molecular mechanism of
saponins in
NAFLD remains unknown. This study aimed to elucidate the effects of ginseng
saponin extract and its
ginsenosides on hepatic steatosis,
fibrosis, and
inflammation and their underlying action mechanism in
NAFLD. Mice were fed a fast food diet (FFD) for 16 weeks to induce
NAFLD and then treated with
saponin extract (50 or 150 mg/kg) for the remaining nine weeks to determine the effects of
saponin on
NAFLD.
Saponin extract administration significantly alleviated FFD-induced hepatic steatosis,
fibrosis, and
inflammation. Particularly,
saponin extract, compared with conventional red ginseng, contained significantly increased amounts of
ginsenosides (Rh1 (10.34-fold) and Rg2 (7.1-fold)). In vitro Rh1 and Rg2 treatments exerted an anti-steatotic effect in primary hepatocytes, an antifibrotic effect in hepatic stellate cells, and anti-inflammatory and pro-mitophagy effects in immortalized mouse Kupffer cells. Mechanistically,
saponin extract alleviated
lipopolysaccharide-induced NLRP3
inflammasome activation by promoting mitophagy. In conclusion,
saponin extract inhibited
inflammation-mediated pathological
inflammasome activation in macrophages, thereby preventing
NAFLD development. Thus,
saponin extract administration may be an alternative method for
NAFLD prevention.