Astragaloside IV Improves High-Fat Diet-Induced Hepatic Steatosis in Nonalcoholic Fatty Liver Disease Rats by Regulating Inflammatory Factors Level via TLR4/NF-κB Signaling Pathway.

Objective: Astragaloside IV (AS-IV) is the primary bioactive component purified from Astragalus membranaceus which is one of the traditional Chinese medicines. Research studies found that AS-IV has significant pharmacological effects on focal cerebral ischemia/reperfusion, cardiovascular disease, pulmonary disease, liver cirrhosis, and diabetic nephropathy, but little is known about the effects of AS-IV on nonalcoholic fatty liver disease (NAFLD). In this study, we investigated whether AS-IV has beneficial effects on NAFLD in rats and its potential mechanisms. Methods: Male SD rats were fed with high-fat diet (HFD) for 12 weeks to establish NAFLD rat model, and then, the rats were divided into five groups. The control group rats were fed with normal diet for 12 weeks and then were given normal saline (1.0 ml kg-1 day-1) by intragastric administration for 4 weeks. The model group rats were fed with HFD for 12 weeks and then were given normal saline (1.0 ml kg-1 day-1) by intragastric administration for 4 weeks. The AS-IV-L, AS-IV-M, and AS-IV-H groups were treated with 20, 40, and 80 mg kg-1 day-1 of AS-IV by intragastric administration for 4 weeks and given HFD diet. Then, we detected serum transaminase (ALT, AST), blood lipid (TG, TC), inflammatory cytokines (IL-6, IL-8 and TNF-α), liver histology(NAFLD activity score), TLR4/MyD88 signaling pathway in liver tissue. Results: We found AS-IV significantly reduced serum levels of AST, ALT, TG, TNF-α, IL-6, and IL-8 in NAFLD rats and downregulate the expression of TLR4 mRNA, MyD88 mRNA, NF-κB mRNA, and proteins in liver tissue. Moreover, AS-IV could significantly reduce the NAFLD activity score of NAFLD rat liver. Conclusion: In this study, we demonstrated that AS-IV have a protective effect on NAFLD by inhibiting TNF-α, IL-6 and IL-8 levels and down-regulating TLR4, MyD88 and NF-κB expression in rat liver tissues.

Effects of telmisartan on improving leptin resistance and inhibiting hepatic fibrosis in rats with non-alcoholic fatty liver disease.

The present study aimed to investigate the impacts of telmisartan (TEL) on hepatic fibrosis, serum leptin, leptin protein in liver tissue and its mRNA expression level in rats with non-alcoholic fatty liver disease (NAFLD). Male Sprague Dawley rats were randomly divided into the control (N), model (M), polyene phosphatidylcholine (P) and TEL (T) groups. Group M and the intervention groups were given a high-fat diet for 12 weeks to induce NAFLD, followed by 4 weeks of intragastric administration of normal saline (1.0 ml/kg/day), polyene phosphatidylcholine (PPC; 123.1 mg/kg/day) and TEL (8 mg/kg/day). The liver tissue was then assessed for the NAFLD activity score and fibrosis score (FS), and serum biochemistry and leptin levels were determined. Additionally, leptin protein expression levels were examined by western blotting and the expression of leptin mRNA was investigated by reverse transcription-polymerase chain reaction. TEL significantly improved FS in rats (P<0.01) and was more effective than PPC. TEL significantly reduced the expression of serum leptin, as well as the expression levels of leptin protein and its mRNA in liver tissue (P<0.01); however, the effects of PPC were not significant (P>0.05). TEL reduced serum leptin, leptin protein and its mRNA in the liver tissue of NAFLD rats, and improved the pathological indicators of liver fibrosis.