Epigallocatechin-3-gallate prevents Non-alcoholic fatty liver disease by modulating liver function, lipid profiles and M1/M2 macrophage polarization

Abstract Background Here, we examine the therapeutic efficacy of Epigallocatechin-3-gallate, the most potent catechin in green tea, on nonalcoholic fatty liver disease (NAFLD), a growing epidemic in humans. Methods NAFLD was induced by high-fat diet (HFD) with 30% fructose in drinking water for 8 weeks. Mice were divided into 3 groups: model group (MD; no EGCG), low dose EGCG group (LE, 20 mg/kg/d) and high dose EGCG group (HE, 50 mg/kg/d). Liver histology, serum lipid prolife, liver function as well as liver M1/M2 polarization were evaluated. Results At the end of the experiment, the mean body weight of LE and HE mice were 39.7g and 45.7g, while it was 51.9g in the MD group (P< 0.05). Similarly, liver weights in the LE and HE groups (means = 1.44g, and 1.68g, respectively) were lower than that in MD (2.94g, P < 0.01). Liver dysfunction observed in the MD group (mean AST=133.2 U/L and ALT=183.4 U/L), was significantly improved in both LE (44.8 U/L, 86.8 U/L, respectively, P < 0.001) and HE groups (83.63 U/L, 117.6 U/L, respectively P < 0.05). Serum cholesterol, HDL, triglyceride levels were increased in the MD group, but lowered in both LE and HE mice (p<0.01). Hepatic FACS, RT-PCR and IHC studies demonstrated that the HE group had lower F4/80+ CD86+ (0.3 ×103 vs 1.5 × 104), F4/80+ MHC II+ (0.7 ×104 vs 1.3 × 104), and higher F4/80+ CD206+(2.96 ×104 vs 0.3 × 104), F4/80+ CD23+ (1.27 ×104 vs 0.65 × 104) hepatic infiltration, accompanied by down-regulated CD68 and up-regulated CD163 mRNA expression. Conclusion EGCG subdued NAFLD despite consumption of HDF and high fructose water, marked by improved liver function and serum lipid profile, as well as M1/M2 polarization. EGCG should be investigated as a therapeutic modality in human NAFLD.