Background and Objective: Metabolic dysfunction-associated fatty liver disease (MAFLD) is now widely recognized as the hepatic presentation of the metabolic syndrome. Owing to the well-established anti-inflammatory and antioxidant properties of thymoquinone, the current study was conducted to assess the effect of thymoquinone on serum liver enzyme activities, lipid profile parameters, as well as the transcriptional expression of key genes involved in inflammatory and antioxidant signaling pathways, using an animal model of MAFLD.
Methods: In this interventional-experimental animal study, 18 rats were randomly divided into 3 groups of 6: healthy control, experimental 1, and experimental 2. With the exception of the healthy control group, all animals were subjected to a high-fat diet over an eight-week period. Experimental group 2 received oral administration of thymoquinone at a dose of 10 mg/kg body weight for 35 days, while experimental group 1 received no therapeutic intervention. At the end of the experiment, tissue and serum samples were collected for colorimetric biochemical analyses (ALT, AST, cholesterol, triglyceride, LDL, HDL), RT-PCR measurement of NRF2, VCAM, ICAM, and NFkB gene expression, and histological examination.
Findings: The results of study demonstrated that thymoquinone treatment significantly decreased serum levels of ALT (94.5±10.85) and AST (202.16±32.12) compared to the MAFLD group (p<0.001). Thymoquinone also reduced cholesterol (257±50.37, p<0.003), triglycerides (90.16±12.73, p<0.007), and LDL (51.26±15.19, p<0.001), and increased HDL (48.83±6.5, p<0.001). Gene expression analysis revealed significant downregulation of VCAM (1.02±0.49, p<0.001), ICAM (0.89±0.16, p<0.001), and NFκB (1.44±0.44, p<0.003), and significant upregulation of NRF2 (0.99±0.22, p<0.001) following thymoquinone treatment compared to the MAFLD group. Histological assessments showed considerable improvement in tissue damage.
Conclusion: Based on the results of this study, thymoquinone can exert protective effects in MAFLD through the amelioration of lipid profile and hepatic enzyme levels.