Effects Of Polygonatum Fermented Products On Glucose And Lipid Metabolism In C57BL/6 Diabetic Mice And Its Molecular Mechanism

Polygonatum sibiricum（PS）belongs to the Liliaceae family.It was a traditional chinese medicine that nourishes and strengthens the body and delays aging.Modern research showed that PS can lastingly lower blood pressure,blood glucose and triacylglycerol,and could also prevent fatty liver and coronary heart disease.PS contains a variety of biological components,such as small saccharides,polysaccharides,saponins,alkaloids,flavonoids,lignin and amino acids.Among them,polysaccharides and saponins were considered to be the main active components of PS,which have various biological effects such as anti-oxidation,anti-inflammatory,lowering blood sugar,and lowering blood lipids.In order to remove the hemp flavor and irritation of raw PS and improve the content of active ingredients in PS,this study used Lactobacillus brevis YM 1301 to fermented PS,and adopted intraperitoneal injection of streptozotocin combined with a high-fat diet to establish T2DM mouse model to evaluate FPS has hypoglycemic,lipid-lowering and anti-inflammatory effects on T2DM mice.In this study,60 male C57BL/6 mice were divided into control group（Control,Ctrl）,diabetes model group（Diabetes model,DM）,metformin treatment group（Metformin,Met）,PS group,low dose of fermented Polygonatum sibiricum（FPSL）,high dose of fermented Polygonatum sibiricum（FPSH）.By detecting fasting blood glucose,insulin,glycosylated hemoglobin,liver glycogen and muscle glycogen levels,assess the effect of FPS in lowering blood glucose.Using Western blot,qRT-PCR and histopathological section staining techniques to detect related lipid metabolism,energy metabolism,inflammatory factors genes and the expression of p-AKT,AKT,p-AMPK and AMPK proteins.To explore the possible mechanisms of FPS for lowering blood glucose,lowering blood lipids,anti-inflammatory and promoting energy balance.Result:1.Fermentation significantly changed the content of polysaccharides and small saccharides.After fermentation,the polysaccharide content in FPS was 8.39%higher than that in PS and the reducing sugar content in FPS was 5.69%lower than that in PS.The glucose and saponin content in FPS were basically unchanged.2.FPS improved blood glucose and blood lipids and other related biochemical indicators.Compared with the DM group,the blood glucose,insulin,glycosylated hemoglobin and liver glycogen levels of the mice in the FPSH group were reduced by 40.07%,46.52%,55.53%and 51.89%,respectively.In addition,the Met,PS,and FPS groups can significantly reduce the levels of TG and LDL.The FPSH treatment group had the largest decrease in LDL levels,which was 55.17%lower than that.of the DM group.3.FPS improved glucose tolerance and insulin sensitivity.In the OGTT experiment,compared with the DM group,the AUCOGTT of the Met and FPSH groups were reduced by 37.98%and 34.12%,respectively.In the ITT experiment,the blood glucose level of the FPSH group at 120 min was only 49%of that of the DM group.Compared with the diabetes group,Met,PS or FPSH treatment reduced the AUCITT of ITT by 47.52%,39.10%and 53.53%,respectively.In addition,the FPS significantly increased the phosphorylation level of AKT.Compared with DM mice,after FPSH treatment,the ratio of p-AKT/AKT in liver and adipose tissue increased by 9.20 and 1.89 times,respectively.4.FPS inhibited lipid accumulation in liver and WAT.In the liver,the size of hepatocyte in DM mice increased by 6 times,while FPSH administration reduced the size of liver cells by 65.18%and adipose cells by 1/3.Moreover,FPS inhibited fat synthesis,promoted fat decomposition and fatty acid oxidation.Compared with DM mice,after FPSH treatment,the expressions of ACC,FAS,SCD1 and FSP27 in the liver were significantly down-regulated to 72.44%,56.38%,16.15%and 5.86%,respectively.In adipose tissue,the expression of FAS,SCD1,FSP27,and PLIN 1 in the FPSH group decreased to 0.84%,1.13%,1.14%,and 5.65%,respectively,while the expression of ATGL and CPT1 increased significantly by 20.91 and 4.43 times,respectively,which were significantly better than PS treatment group.5.FPS inhibited the expression of IL-6,IL-1β,TNF-α and TGF-β inflammatory factors.Among them,FPS has the most significant anti-inflammatory effect in adipose tissue.After FPSH treatment,the levels of IL-6 and TGF-β decreased to 10.43%and 45.46%of the DM group,which were significantly better than the PS treatment group.6.FPS promoted energy consumption and calorie release in diabetic mice.Compared with the DM group,p-AMPK levels increased significantly after FPSH treatment.Compared with the DM group,the expression level of UCP3 in the FPSH group was significantly increased by 6.25 times in the liver.In adipose tissue,the expression levels of UCP1 and UCP3 in the FPSH group were 3.52 times and 25.11 times higher than those in the DM group,respectively.Conclusion:This study revealed a better effect of FPS on glycemic control than PS in diabetic mice.We believed that FPS acted to positively modulate AMPK activation and signaling,ultimately controlling fatty acid oxidation and lipid accumulation.Thus,these results suggested FPS may be a potential functional food benefiting for the prevention and treatment of diabetes,obesity and other metabolic disorders.