Epigallocatechin gallate attenuates fibrosis, oxidative stress, and inflammation in non alcoholic fatty liver disease rat model through TGF/SMAD, PI3 K/Akt/FoxO1, and NF kappa B pathways
PurposeTo investigate the protective mechanisms of an 85 pure extract of epigallocatechin gallate (EGCG) in the development of fibrosis, oxidative stress and inflammation in a recently developed dietary induced animal model of non alcoholic fatty liver disease (NAFLD).MethodsFemale Sprague Dawley rats were fed with either normal rat diet or high fat diet for 8 weeks to develop NAFLD. For both treatments, rats were treated with or without EGCG (50 mg/kg, i.p. injection, 3 times per week) At the end, blood and liver tissue samples were obtained for histology, molecular, and biochemical analyses.ResultsNon alcoholic fatty liver disease (NAFLD) rats showed significant amount of fatty infiltration, necrosis, fibrosis, and inflammation. This was accompanied by a significant expressional increase in markers for fibrosis, oxidative stress, and inflammation. TGF/SMAD, PI3 K/Akt/FoxO1, and NF kB pathways were also activated. Treatment with EGCG improved hepatic histology (decreased number of fatty score, necrosis, and inflammatory foci) reduced liver injury (from ~0.5 to ~0.3 of ALT/AST ratio) attenuated hepatic changes including fibrosis (reduction in Sirius Red and synaptophysin positive stain) with down regulation in the expressions of key pathological oxidative (e.g. nitrotyrosine formation) and pro inflammatory markers (e.g. iNOS, COX 2, and TNF a) EGCG treatment also counteracted the activity of TGF/SMAD, PI3 K/Akt/FoxO1, and NF kB pathways. Treatment with EGCG did not affect the healthy rats.ConclusionsEpigallocatechin gallate (EGCG) reduced the severity of liver injury in an experimental model of NAFLD associated with lower concentration of pro fibrogenic, oxidative stress, and pro inflammatory mediators partly through modulating the activities of TGF/SMAD, PI3 K/Akt/FoxO1, and NF kB pathways. Therefore, green tea polyphenols and EGCG are useful supplements in the prevention of NAFLD.
European Journal of Nutrition