Lycium barbarum Polysaccharide Supplementation Improves Alcoholic Liver Injury in Female Mice by Inhibiting Stearoyl‐CoA Desaturase 1

Scope Lycium barbarum polysaccharide (LBP) is a water fraction of wolfberry, which has been demonstrated to possess a hepatoprotective effect in several liver disease models. However, the anti‐alcoholic liver disease (anti‐ALD) mechanism of LBP has not been investigated thoroughly. Its protective effects on both male and femal mice are investigated in the current study. Methods and results A chronic ethanol‐fed ALD in vivo model is applied to study the effect of LBP in both male and female mice. It is observed that ethanol causes more severe liver injury in female than male mice, and the ameliorative effects of LBP are also more significant in female mice, which are impaired after complete bilateral oophorectomy. The hepatic SCD1 expression is found to be positively correlated with the severity of the liver damage and the main mediator of LBP inducer of protection. The AMPK‐CPT pathway is also activated by LBP to rebalance the dysregulated lipid metabolism during ALD development. By using concurrent sodium palmitate and an ethanol‐induced in vitro cell damage model in AML‐12 cell line, it is characterized that LBP directly interacts with ERα instead of ERβ to activate the SCD1‐AMPK‐CPT pathway. Conclusions LBP is an effective and safe hepatoprotective agent against ALD primarily through the SCD1‐AMPK‐CPT pathway after ERα agonist. The hepatoprotective properties of Lycium barbarum polysaccharide (LBP) have been reported in several disease models. By using in vivo and in vitro ALD alcoholic liver disease (ALD) models and biophysical methods, the sex‐dependent anti‐ALD mechanisms of LBP have been evaluated.