Mogroside Improves Liver Damage In Diabetic Mice By Inhibiting NLRP3

Objective: Diabetes-induced liver damage has become the main cause of non-alcoholic fatty liver disease,mogroside can improve the body’s glycolipid metabolism and liver protection,but its effect on diabetes-induced liver injury has not been elucidated,this study mainly investigates the protective effect of mogroside on diabetes-induced liver injury,and explores its mechanism of action from the NOD-like receptor protein 3(NLRP3)inflamelosome pathway.Methods: The mouse model of type 2 diabetes mellitus was replicated by high-fat diet combined with intraperitoneal injection of Streptozocin(STZ),and the mice were randomly divided into blank group,model group,metformin group(400 mg/kg),mogroside high-dose group(200 mg/kg),mogroside medium-dose group(100 mg/kg),and mogroside low-dose group(50 mg/kg),and intragastric administration for 28 days.The fasting blood glucose values of mice were measured on the 7th,14 th,21st and 28 th days of administration.After the last dose,serum total cholesterol(TC),triglycerides(TG),low density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)were measured.The liver tissue was taken to determine the total cholesterol,triglyceride content,alanine aminotransferase and aspartate aminotransferase levels,and the pathological changes of liver tissue were observed by Hematoxylin-eosin(HE)staining and oil red O staining.At the same time,the content of tumor necrosis factor-α(TNF-α)was measured,and the expression levels of liver NLRP3 and cysteine aspartate proteolytic enzyme-1(caspase-1)were detected by reverse transcription PCR,and the expression level of liver NLRP3,pro-caspase-1,caspase-1,interleukin1β(IL-1β),pro-IL-1β protein expression levels was detected by Western blot.Results: The fasting blood glucose levels in diabetic mice were significantly reduced after treatment with various doses of mogroside(P<0.01).The serum TC,TG and LDL-C contents of mice in each dose group of mogroside were significantly reduced(P<0.001),while the HDL-C content in the medium and high dose groups of mogroside was significantly higher than that in the model group(P<0.01).In addition,the intervention of mogroside significantly reduced the contents of TG,TC and FFA in the liver of diabetic mice(P<0.05).The liver ALT and AST levels of mice in each dose group of mogroside were significantly lower than those in the model group(P<0.01).The results of liver tissue morphological staining showed that the degree of hepatocyte degeneration,edema,necrosis and inflammation in each dose group of mogroside was significantly reduced compared with the model group(P<0.05),and the lipid content of liver tissue was reduced.Moreover,the content of TNF-α in the liver of mice in each dose group of mogroside was significantly reduced(P<0.01).The detection of NLRP3 inflammasome showed that the expression of NLRP3 m RNA in the liver of diabetic mice was reduced by each dose of mogroside(P<0.05,P<0.001),and the high dose of mogroside significantly reduced the expression of caspase-1 m RNA in the liver of mice(P<0.05).The expression of NLRP3,IL-1β protein and the ratio of caspase-1/pro-caspase-1protein in the liver of mice in the medium and high dose groups of mogroside were significantly reduced(P<0.05),and the ratio of IL-1β/pro-IL-1β protein in each dose group of mogroside decreased significantly compared with the model group(P<0.01).Conclusion(s): Mogroside can significantly reduce blood glucose and improve lipid metabolism disorders in high-fat diet combined with STZ-induced diabetic mice.At the same time,it reduces liver damage caused by diabetes,and abnormal lipid metabolism,protects liver tissue,and its mechanism of action is related to inhibiting the activation of NLRP3 inflammasomes in the liver,thereby reducing the release of inflammatory factors.