Pakistan Journal of Pharmaceutical Sciences

Abstract: In preliminary studies, Anethole Dithiolethione (ADT) has exhibited significant potential in reducing the accumulation of reactive oxygen species (ROS) and regulating mitochondrial fusion (Mfn) in relation to non-alcoholic fatty liver disease (NAFLD). This study sought to investigate the specific role of ADT in NAFLD using a mouse model, with C57BL/6J mice divided into four groups: normal diet, high-fat diet (HFD), HFD with 10 mg/kg ADT, and HFD with 30 mg/kg ADT. Pathological changes were assessed through oil red O and hematoxylin-eosin staining. Lipidomics profiling was conducted to determine the composition of phospholipids and real-time reverse transcription polymerase chain reaction and western blotting were utilized to analyze gene and protein expression related to liver phospholipid transport, endoplasmic reticulum (ER) stress and lipid synthesis. The results revealed that ADT increased the levels of phospholipid components such as phosphatidylserine and phosphatidylethanolamines, as well as the expression of relevant genes associated with liver lipid metabolism and ER stress (Mfn2, ATF6, PTDSS1, PTDSS2 and PPAR?). ADT also demonstrated the ability to decrease levels of liver inflammatory indicators and oxidative stress induced by the HFD, including ALT, AST, IL-6, TNF-?, MDA and catalase. These findings suggest that ADT shows promise as a potential treatment for NAFLD by regulating Mfn2 expression and promoting phosphatidylserine transfer.