Exploring the Mechanism of Sesamin in Treating Mild Alcoholic Liver Disease Based on Transcriptome Sequencing

Background: Sesamin has been shown to prevent and treat alcoholic liver disease (ALD), but the underlying mechanisms remain unclear. This study aims to observe the effects of sesamin on mild ALD and to explore its potential mechanisms. Methods: Twenty-one male SD rats were divided into three groups: normal control, mild ALD without sesamin, and sesamin-treated mild ALD. A mild ALD model was induced by alcohol; the treated group received 160 mg/kg/day sesamin. After 8 days, liver morphology was assessed by ultrasound, and blood/liver samples were collected. Serum total bile acids (TBA), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were tested. Liver pathology was visualized using HE and Masson staining. mRNA seq, qPCR, and western blotting validated mRNA and protein changes. Results: Following sesamin administration, a statistically significant decrease in serum TBA levels was observed in rats with mild alcoholic liver disease ( P < .05). However, no significant alterations were detected in the levels of AST ( P > .05) and ALT (P > .05). Among the normal, mild ALD model group, and sesamin-treated mild ALD group, 442 common differential mRNAs in the liver were found, and those related to bile acid metabolism were identified as Slco1b2 , Abcc3 , Abcb4 , Slc27a2 , Baat , and Nr1d1 . Compared to the model group, the sesamin-treated mild ALD group showed a significant increase in liver Slco1b2 ( P < .05) and Nr1d1 ( P < .01) mRNA expression, a significant decrease in Abcc3 mRNA expression ( P < .05), a significant increase in Oatp1b2 ( Slco1b2 ) and REV-ERBα ( Nr1d1 ) protein expression ( P < .05), and a significant decrease in MRP3 ( Abcc3 ) expression ( P < .01). Conclusion: Sesamin may exert its protective effects against mild ALD by modulating the expression of Nr1d1 (REV-ERBα), Slco1b2 (OATP1), and Abcc3 (MRP3) which results in a reduction of serum bile acid levels.