Abstract:

AIM: To observe the regulatory effect of total glucosides of paeony (TGP) on the HMGB1 and RAGE pathway (NAFLD) in rats with nonalcoholic fatty liver disease.  METHODS: High fat and high fructose diet were administered to induce NAFLD rat models. The model rats were randomly divided into NAFLD group, TGP high (200 mg·kg-1·d-1) and low dose group (100 mg·kg-1·d-1), Metformin group (200 mg·kg-1·d-1), Silybin group (200 mg·kg-1·d-1), and another blank control group was established. the rats total Cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triglyceride (TG), free fatty acid (FFA), alanine aminotransferase (ALT), aspartate amino shifting enzyme (AST), fasting blood glucose (FBG), postprandial 2 hours blood glucose (2 hBG), insulin (fins) were observed 6 weeks after medication, and the insulin resistance index (HOMA-IR) and liver index were thence calculated. Western blot was applied to detect the high mobility group protein 1 (HMGB1) and the receptor of advanced glycation end products (RAGE) protein in liver tissue. RESULTS:Compared with model group, the contents of 2 hBG, fins, HOMA-IR, LDL-C, TC, TG, FFA, ALT, AST, GST were decreased in high and low dose TGP groups（P<0.05 or P<0.01）. High and low dose of TGP groups presented fair effect in antagonizing insulin resistance, lowering lipid and blood glucose as well as improving liver function. Also, TGP high and low dose group can down-regulate the expressions of HMGB1 (P<0.01) and RAGE (P<0.05 ) proteins. CONCLUSION: TGP can improve the metabolism of glucose and lipid, antagonize the insulin resistance, enhance the insulin sensitivity and improve the role of liver function in NAFLD rats through inhibition of HMGB1, RAGE signaling pathway.

Key words: total glucosides of paeony, nonalcoholic fatty liver, signaling pathway, high mobility group box-1 protein, receptor for advanced glycation end-products protein