The Effects Of Total Flavonoids Of A. Chinensis On Hepatic Insulin Resistance And PI3K/AKT/FoxO1 Pathway In Db/db Mice

ObjectiveBy observing the effect of Cyclocarya flavonoids extract on the glucose and lipid metabolism of spontaneous type 2 diabetic db/db mice,and based on the Pi3k/AKT/FOXO1 pathway,the mechanism of Cyclobalanopsis flavonoids extract on liver insulin resistance was explored and provide experimental basis for clinical application.MethodUsing a randomized control design method,30 spontaneous type 2 diabetes animal model db/db mice were selected for the animal experiment.Random blood glucose>11.1mmol/L measured on different days was screened and included in the experiment,and divided into the experiment according to the random method of weight and blood glucose block:Model group(DM),metformin group(Met),Cyclocarya flavonoids extract group(CPF),8 mice in each group.At the same time,8 mice of the same age(Leprdb)wt/wt wild type(Wild Type)were set as the normal control group(NC),and the continuous intervention was carried out for 6 weeks,and the OGTT test was carried out in the 5th week.In the experiment,the general condition of mice,fasting blood sugar,body weight,and food intake were observed.After 6 weeks,the mice were collected,and the serum was obtained to detect the related indicators of glucose and lipid metabolism.HE staining and PAS staining were performed on the fixed liver tissue to observe the tissue morphology and glycogen content;the frozen liver was used to detect the protein expression of the liver Pi3k/AKT/FOXO1 signaling pathway by Western Blot method.Results1.General condition monitoring:In the experiment,the mice in the normal group were in good condition,with the characteristics of fast action,flexible response,dark and shiny fur.The mice in the model group and the Cyclocarya chinensis treatment group showed polydipsia,polyphagia,polyuria,slow movement,slow response,and dull fur.The performance of Cyclocarya flavonoids after 6 weeks of intervention was significantly improved compared with the model group.As shown in Table 1 and Figure 1,during the experiment,the average food intake of the model group and the Cyclocarya total flavonoids group was significantly higher than that of the normal group,and the average food intake of the administration group was not statistically different from that of the model group.2.Serum test:The related indicators of glucose and lipid metabolism in normal mice are normal,and there is no insulin resistance.However,the model group has obvious glucose and lipid metabolism disorders:FBG,FINS,HOMA-IR,and blood lipid indexes(TC,TG,HDL)have increased significantly(P<0.01 or P<0.05),and LDL has an upward trend;compared with the model group,Cyclocarya flavonoids significantly reduced FBG,FINS,TC and LDL(P<0.01 or P<0.05).3,Morphological examination of liver tissue:HE staining showed that CPF can significantly improve liver steatosis,improve the morphology and structure of liver cells,and reduce inflammatory infiltration.Glycogen(PAS)staining showed that the total flavonoids treatment group of Cyclocarya paliurus promoted glycogen synthesis.4.Western Blot:Compared with the normal group,the expression of PI3Kp85,p-AKT,and p-FoxO1 protein in the liver of db/db mice in the model group were significantly reduced,and FoxO1 protein was significantly increased(P<0.05 or P<0.01).Compared with the model group,the protein expressions of PI3K,p-AKT,and p-FoxO1 in the liver of the Cyclocarya flavonoids group were significantly increased(P<0.01 or P<0.05),and the protein expression of FoxO1 was significantly inhibited(P<0.01).Conclusion1.The total flavonoids of Cymbidium aquilinum can significantly improve glucose and lipid metabolism disorders and insulin resistance in db/db mice.2.The total flavonoids of Cyclocarya can significantly improve liver steatosis in db/db mice.It can significantly improve the morphology and structure of liver cells,reduce inflammation infiltration,and promote liver glycogen synthesis.3.The mechanism of Cyclobalanopsis flavonoids improving IR may be to promote the signal transmission of liver insulin,enhance the protein expression of PI3K,p-AKT,and p-FoxO1,and inhibit the protein expression of FoxO1.