Abstract

Nonalcoholic fatty liver disease (NAFLD) represents the most prevalent chronic liver disease, yet there remains an unmet need for effective therapeutic interventions. This study aimed to investigate the hepatoprotective effect of Ophiopogonis japonicus polysaccharides (OJPs) on NAFLD and its mechanism. The benefits of OJPs or the positive drug fenofibrate in NAFLD were assessed in mice fed a high-fat diet (HFD). AML12 cells were induced with PA/OA to construct an in vitro model, and the benefits of OJPs were assessed in terms of oil red O staining, BODIPY staining, changes in the expression of lipid accumulation-related proteins, iron metabolism-related proteins, and oxidative stress analysis. OJPs significantly alleviated lipid accumulation and oxidative stress in PA/OA-induced AML12 cells, and maintained iron metabolism in the liver of HFD-induced mice, but the benefits of OJPs were reversed after exogenous inhibition of Runt-related transcription factor 3 ( Runx3) . More importantly, knockdown of Runx3 combined with overexpression of ATP-binding cassette transporter 7 ( Abcb7) again restored the benefit of OJPs. Runx3 transcriptionally activates Abcb7 by binding to its promoter. The findings suggest that OJPs could serve as a pharmaceutical intervention for NAFLD through the Runx3/Abcb7 axis. This discovery unveils an unexplored association between iron metabolism and hepatic disease.