Epigallocatechin-3-gallate (EGCG) has been shown to attenuate obesity, fatty liver disease, hepatic inflammation and lipid profiles. Here, we validate the efficacy of EGCG in a murine model of non-alcoholic fatty liver disease (NAFLD) and extend the mechanistic insights. NAFLD was induced in mice by a high-fat diet (HFD) with 30% fructose. EGCG was administered at a low dose (25 mg/kg/day, EGCG-25) or high dose (50 mg/kg/day, EGCG-50) for 8 weeks. In HFD-fed mice, EGCG attenuated body and liver weight by ~22% and 47%, respectively, accompanied by ~47% reduction in hepatic triglyceride (TG) accumulation and ~38% reduction in serum cholesterol, resonating well with previous reports in the literature. In EGCG-treated mice, the hepatic steatosis score and the non-alcoholic steatohepatitis activity score were both reduced by ~50% and ~57%, respectively, accompanied by improvements in hepatic inflammation grade. Liver enzymes were improved ~2–3-fold following EGCG treatment, recapitulating previous reports. Hepatic flow cytometry demonstrated that EGCG-fed mice had lower Ly6C+, MHCII+ and higher CD206+, CD23+ hepatic macrophage infiltration, indicating that EGCG impactedM1/M2 macrophage polarization. Our study further validates the salubrious effects of EGCG on NAFLD and sheds light on a novel mechanistic contribution of EGCG, namely hepatic M1-to-M2 macrophage polarization. These findings offer further support for the use of EGCG in human NAFLD.

Background Rheumatoid arthritis is an autoimmune disorder in which the immune system attacks its own tissues, resulting in swelling and inflammation of the joints. Hemopexin (Hx), an acute-phase protein synthesized by hepatocytes in response to proinflammatory cytokines, binds to heme, and controls heme-iron availability in tissues and T lymphocytes. Its absence has been associated with increased inflammatory properties of high-density lipoproteins and the development of autoimmune disease, such as experimental autoimmune encephalomyelitis (EAE). The aim of this study is to investigate the role of Hx in the development of arthritis using the collagen antibody-induced arthritis (CAIA) mouse model. Methods CAIA was induced in Hx-deficient (Hx−/−) mice and wild-type (WT) littermates, via i.p injection of antibodies directed against type II collagen, followed by the administration of lipopolysaccharide (LPS). Paw thickness and disease severity was evaluated daily. Blood samples were collected to measure the serum Hx levels using ELISA. Results During CAIA, serum Hx level became elevated and remained high. When CAIA was induced in Hx−/− mice, they exhibited reduced arthritis compared to WT mice, as arthritic Hx−/− mice had lower average paw thickness (1.32 ± 0.02 vs 2.67 ± 0.05, 2-tail t test, P < 0.05 ) and reduced arthritis scores ( 2.0 ± 0.5 vs 7.3 ±1.25, 2-tail t test, P < 0.01) at the end of the experiment compared to WT mice. Pathology studies are in progress. Conclusion Hx−/− mice are protected from CAIA, with reduced arthritis, indicating a pro-inflammatory role for Hx in the development of arthritis. Further studies are warranted to unravel the pathogenic mechanisms involved and clinical relevance of this molecule.

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.