Anti-inflammation effect via TLR4-mediated MyD88-dependent and -independent signalling pathways in non-alcoholic fatty liver disease rats: Chinese herb formula

Non-alcoholic fatty liver disease (NAFLD) is a global health problem that has been the most common cause of chronic liver disease. No promising treatment has been recommended. Toll-like receptor 4 (TLR4) is the essential factor in pathogenesis and closely linked to non-alcoholic steatohepatitis. In this study, we expected to explore the potential effect of Hongqi Jiangzhi Formula (HJF) in alleviating inflammation via TLR4-mediated MyD88-dependent and -independent signalling pathways in NAFLD rat liver tissue. In total, 32 rats were randomized into 4 groups: Normal, Model, Probiotic and HJF groups, except the normal group, which was fed a chow diet, while the other three groups were all fed a high fat diet (HFD). The probiotic and HJF group were additionally fed probiotic and Hongqi Jiangzhi Formula, respectively. The course of treatment was 16 weeks. Basic characteristics of the rats were measured before sacrifice. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), triglyceride (TG), fasting glucose (GLU) and insulin in the aorta serum was measured, and the HOMA-IR (homeostasis model of assessment for insulin resistance index) was calculated. Tumour necrosis factor-alpha in the serum was also measured by means of an enzyme-linked immunosorbent assay. The liver tissues were stained with Haematoxylin-Eosin. Protein expression of MyD88-dependent and -independent signalling pathways, including TLR4, TIRAP, MyD88, p-NF-kappa B, NF-kappa B p65, TRAM, pIRF3 and IRF3, were further detected by Western blotting. Compared with the model group, HJF could reduce the level of the body weight, ALT, HOMA-IR index, insulin, AST, TG and TNF-alpha significantly. Regarding the proteins in TRL4 downstream pathways, HJF could down-regulate the overexpression of TLR4, TIRAP, MyD88, p-NF-kappa B and TRAM, TRIF, and pIRF3. In conclusion, HFD can activate TLR4 MyD88-dependent and -independent pathways, which might be related to the inflammatory production of NF-kappa B. HJF could effectively improve lipid accumulation in the high-fat rat liver and could down-regulate the expression of NF-kappa B through TLR4 downstream signalling pathways.