| Silymarin, the seed extract of milk thistle (Silybum marianum ), is a mixture of polyphenolic flavonolignans and is a hepatoprotective agent. We hypothesized that Silymarin might modulate mediators, such as the nuclear transcription factors, Sterol Regulatory Element Binding Protein-1 (SREBP-1), Carbohydrate Response Element Binding Protein (ChREBP) and Nuclear factor-kappaB (NF-kappaB), and the hormone, adiponectin, that are involved in the molecular mechanisms of Non-Alcoholic Fatty Liver Disease (NAFLD). C57BL/6, male mice were fed with a standard chow diet or a high carbohydrate diet (HCD) for 5 months and treated with the different doses of silymarin from diet or by gavage. Silymarin improves the antioxidant status in the liver and positively affect plasma lipid profile in mice fed HCD, especially silymarin resulted in the reduction of TBARS, elevated GSH and SAMe contents in the liver. HCD increased the LPS-induced release of tumor necrosis factor-alpha (TNF-alpha) and decreased the secretion of adiponectin. Silymarin decreased the release of LPS-induced TNF-alpha and increased the secretion of adiponectin. HCD increased the levels of P65 in the nuclear extract and p-IkappaB-alpha in the cytosolic extract, the levels of SREBP-1, the levels of ChREBP, and the expression of FAS; high dose of silymarin by gavage decreased their levels. In summary, we successfully developed a fatty liver mouse model by feeding a HCD for a 5-month period. This study indicated that silymarin suppressed oxidative stress induced by HCD and positively influenced hepatic steatosis and liver injury, at least in part, by blocking the increase in SREBP-1, ChREBP, P65 and p-IkappaB-alpha levels, the expression of fatty acid synthase (FAS) and stimulating the secretion of adiponectin in mice. Our data provide a rationale for further exploration of the potential use of silymarin as an alternative and supportive therapy in the treatment of liver disorders such as NAFLD/NASH. |
