tilianin and Non-alcoholic-Fatty-Liver-Disease

Non-alcoholic fatty liver disease (NAFLD) has emerged as one of the most frequent types of liver disease in pediatric populations with obesity. Tilianin has multiple biological activities including anti-inflammatory and antioxidant. Here, we aim to explore the functions and possible mechanisms of tilianin on NAFLD in obese children. A high-fat high-carbohydrate (HFHC) diet was used to feed 21-d-old mice. Tilianin was administered at a dose of 10 or 20 mg/kg daily. HFHC-fed mice gained weight, increased liver index. The liver showed hepatocyte ballooning, inflammatory infiltration, and steatosis. Elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) and reduced the high-density lipoprotein cholesterol (HDL-C) level were found in HFHC-fed mice. Administration of tilianin significantly reduced these impairments. We further evaluated proteins related to lipid metabolism and observed that LXRα, SREBP-1c, FAS and ACC1 expression were blunted following tilianin administration. In addition, tilianin suppressed reactive oxygen species (ROS) overproduction and lipid peroxide 4-Hydroxynonenal expression, ascribed to its oxidative stress-modulating capacity. Tilianin also reversed the increase in F4/80 expression and proinflammatory cytokine levels. Of note, tilianin administration resulted in decreased protein levels of active caspase-1 and NOD-like receptor protein 3 (NLRP3) in HFHC-fed mice. Our study suggests that tilianin may ameliorate NAFLD in early obese mice by modulating lipids metabolism, oxidative stress, and inflammation, which may in part involve inhibiting NLRP3 inflammasome activation.

Topics: Animals; Cholesterol, LDL; Flavonoids; Glycosides; Mice; Mice, Obese; NLR Family, Pyrin Domain-Containing 3 Protein; Non-alcoholic Fatty Liver Disease

The understanding and treatment of nonalcoholic steatohepatitis (NASH) are still very limited. This study reports the therapeutic effect of tilianin on mice with NASH and further explores its possible molecular mechanisms. A mice model of NASH was established using low-dose streptozotocin combined with a high-fat diet and tilianin treatment. Liver function was assessed by determining serum aspartate aminotransferase and alanine aminotransferase in serum. Interleukin (IL)-1β, IL-6, transforming growth factor β1 (TGF-β1), and tumor necrosis factor α (TNF-α) levels in serum were determined. Hepatocyte apoptosis was assessed using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling staining. Oil Red O staining and boron dipyrrin staining were used to determine lipid deposition in liver tissues. Masson staining was used to evaluate liver fibrosis, and immunohistochemistry and western blot analysis were used to determine the expression of target proteins. Tilianin treatment significantly ameliorated liver function, inhibited hepatocyte apoptosis, and reduced lipid deposition and liver fibrosis in mice with NASH. The expression of neuronatin (Nnat) and peroxisome proliferator-activated receptor (PPAR) α was upregulated, whereas that of sterol regulatory element-binding protein 1 (SREBP-1), TGF-β1, nuclear factor (NF)-κB p65, and phosphorylated p65 was downregulated in the liver tissues of mice with NASH after tilianin treatment. The above effects of tilianin were significantly reversed after Nnat knock-down, but its effect on PPARα expression was unaffected. Thus, the natural drug tilianin shows potential in treatig NASH. Its mechanism of action may be related to the targeted activation of PPARα/Nnat, thereby inhibiting the activation of the NF-κB signaling pathway.

Topics: Animals; Lipids; Liver; Liver Cirrhosis; Membrane Proteins; Mice; Mice, Inbred C57BL; Nerve Tissue Proteins; NF-kappa B; Non-alcoholic Fatty Liver Disease; PPAR alpha; Transforming Growth Factor beta1