In current study, we aimed to investigate whether the
gentiopicroside (GPS) derived from Gentiana manshurica Kitagawa could block the progression of alcoholic hepatic steatosis to
fibrosis induced by chronic
ethanol intake. C57BL/6 mice were fed an
ethanol- containing Lieber-DeCarli diet for 4 weeks. LX-2 human hepatic stellate cells were treated with GPS 1 h prior to
transforming growth factor-β (TGF-β) stimulation, and murine hepatocyte AML12 cells were pretreated by GPS 1 h prior to
ethanol treatment. GPS inhibited the expression of
type I collagen (
collagen I), α-smooth muscle actin (α-SMA) and tissue inhibitor of
metal protease 1 in
ethanol-fed mouse livers with mild
fibrosis. In addition, the imbalanced lipid metabolism induced by chronic
ethanol-feeding was ameliorated by GPS pretreatment, characterized by the modulation of
lipid accumulation. Consistently, GPS inhibited the expression of
collagen I and α-SMA in LX-2 cells stimulated by TGF-β. Inhibition of
lipid synthesis and promotion of oxidation by GPS were also confirmed in
ethanol-treated AML12 cells. GPS could prevent hepatic steatosis advancing to the inception of a mild
fibrosis caused by chronic alcohol exposure, suggesting GPS might be a promising
therapy for targeting the early stage of
alcoholic liver disease.