The Protective Effects Of Polygonatum Sibricum Aqueous Extract On Glycolipid Metabolism In Mice Based On PI3K/AKT Pathway

Objective C57 male mice was given Polygonatum sibiricum aqueous extract(PSAE)by gavage.The development of diabetes in mice is simulated by a high-fat diet combined with multiple low-dose intraperitoneal injection of streptozocin which aim to investigate the protective effect of Polygonatum sibiricum aqueous extract and its possible mechanism on glycolipid metabolism during the development of diabetes.Methods 4 week male C57 BL mice fed with standard diet for two weeks adaptability and then mice were randomly divided into blank Control group,Model group(Model),the PSAE low-dose group(0.5 g/kg,LPSAE group),PSAE dose group(1 g/kg,MPSAE group),PSAE high dose group(group 2 g/kg,HPSAE)and rhizoma polygonati polysaccharide group(0.75 g/kg,PSP group).During feeding,mice in PSAE groups and PSP group were given PSAE or PSP by gavage.The mice in the control group and the model group were given the same volume of solvent by gavage as the same control group.The body weight of the mice was measured regularly every week.After one week of intragastric administration,mice in model group PSAE dose group PSP group were fed with 60% high fat diet.6 weeks later,the mice in the control group were intraperitoneally injected with 1%STZ at a dose of 35mg/kg after consecutive 3 days of overnight fasting without water.The mice in the control group were fed standard diet throughout the whole course,and the same volume of solvent was injected intraperitoneally as the same surgical control.1 week later,the mice was overnight fasting water to detect the fasting blood glucose(FBG)and postprandial blood glucose tolerance curve.The second day mice were killed and mice serum was collected to detect the level of fasting serum insulin(FINS),serum cholesterol(TC),serum triglyceride(TG),serum low density lipoprotein-cholesterol(LDL-C)and the level of blood hemoglobin A1c(Hb A1c)was detected in mice blood.Mice liver was weighed and then part of liver tissue was fixed in paraformaldehyde for Oil red O staining and PAS staining while the others was saved in-80 ℃.The content of triglyceride in liver tissue was measured by the enzyme marker.The m RNA level of related genes were test by RT-PCR.Western blotting was used to dectect the IRS1,PI3 K,AKT,GSK-3 protein level and phosphorylated protein levels of related protein in mice liver.Results Compared to control,the glucolipid metabolism was significantly impaired in the model group.Specifically,the level of FBG,FINS,HOMA-IR,area under the postmeal glucose tolerance curve(AUC),Hb A1 C and other glucose metabolism indexes in the model group mice all showed significant increases(P<0.01).Further more,mice weight and the level of TG,TC,HDL-C,LDL-C,liver TG were significantly increased(P<0.01).Meanwhile in Model mice,the results of oil red O staining in liver tissue sections showed obvious lipid deposition(P<0.01).In detail,in PSAE group mice,the level of FBG,FINS,Hb A1 c,HOMA-IR,AUC,Hb A1 c were lower significantly than Model group and the lipid metabolism indexes inculding mice weight,the level of TG,TC,LDL-C,liver TG were all significantly lower than Model group mice.At the same time,liver oil-red O staining of PSAE group showed significant improvement in lipid deposition,while PAS staining showed significant increase in glycogen synthesis,and both showed dose dependence.The results of the mechanism study showed that the m RNA levels of the upstream and downstream gene IRS1,PI3 K AKT,GSK-3β and the protein level of the above genes and the phosphorylation level of related proteins in HPSAE group mice were all higher than the mice in Model group.In addition,PSP group mice which is set as positive control showed the similar effect on all the indexes with HPSAE group mice and there is no significant difference between the two groups.Conclusions PSAE can effectively regulate blood glucose and lipid levels in mice which illustrated that PSAE can protect the fuction of glucose and lipid metabolism in mice and it is of great guiding significance for the prevention of diabetes.This protective effect may be coused by enhancement of PI3K/AKT pathway and the related phosphorylated proteins.