AbstractThe study aimed to examine the effect of ginseng polysaccharide (GP) on acute alcoholic liver injury (AALI) and determine its underlying molecular mechanism. GP's in vitro and in vivo hepatoprotective effects were evaluated using LO2 cells and alcohol‐induced C57BL/6 male mice. Cell Counting Kit‐8, immunofluorescence, hematoxylin‐eosin, immunohistochemistry, and Western blot (WB) were used to detect alcohol‐induced lipid metabolism and autophagy levels in LO2 cells and liver. It was mainly composed of glucose, galactose, and arabinose in a molar ratio of 12.9:1.6:1.0. Experiments in vitro demonstrated that administration of GP to LO2 cells significantly increased the alcohol‐induced increase in cell viability. In addition, it can inhibit lipogenesis, enhance lipolysis, and stimulate autophagy. In alcohol‐induced mice, GP also inhibited hepatic histological lesions, prevented alanine aminotransferase and aspartate aminotransferase elevation, improved abnormal lipid metabolism, and boosted hepatocyte autophagy. In vivo and in vivo analysis of the underlying mechanisms revealed that GP promotes the expression of proteins in autophagy in AALI thereby alleviating it.