Pharmacological And Metagenomic Evidences For The Alleviation Of Insulin Resistance By Polygoni Multiflori Radix Preparata

Object:Insulin resistance is the core of metabolic syndrome,which is the main clinical characteristic of type 2 diabetes.Long-term abnormal levels of blood glucose can induce hypertension,renal insufficiency and increase the risk of angiocardiopathy.It is also an important variety included in the Pharmacopoeia of the people's Republic of China(2015 edition).It has the functions of soothing the mind,nourishing blood,activating collaterals,detoxifying.Polygoni Multiflori Radix Praeparata(PMRP)can replenish the essence and blood,black hair,strengthen the muscles and bones,and replenish the liver and kidney,as a tonic medicine.This study focused on the effects of PS and TSG on insulin resistance induced by high fat and high sugar diet,and elucidated its mechanism.It provides an important basis for the application of PMRP in the prevention and treatment of insulin resistance.Method:70 SD rats were randomly divided into normal group(CON),high-fat and high-sugar diet group(MOD),metformin hydrochloride group(MET),total Polysaccharide group(PS.L,PS.H),TSG group(TSG.L,TSG.H),10 rats in each group.IR was induced by high fat and high sugar diet,and the diet lasted for 12 weeks.During the experiment,the daily food intake,body weight and fasting blood glucose level were recorded.Oral glucose tolerance(OGTT)test was performed at the end of the experiment,and the rats were killed to take the liver for pathological section after the end of the experiment.To evaluate and the regulation of IR in Polygoni Multiflori Radix Preparata,The contents of insulin,glucagon,total cholesterol,triglyceride,high density lipoprotein(HDL-C)and low density lipoprotein(LDL-C)in plasma of rats were determined by ELISA.The analyses of ?-diversity and function of gut microbes,species annotation and abundance were carried out to reveal the regulation of PS and TSG on gut microecology.To evaluate he effects of PS and TSG on the related regulatory proteins,the contents of GPR43 and p-AMPK in rat liver and skeletal muscle were detected by Western blot.Results:Effects of PS and TSG on insulin resistance: PS and TSG could significantly reverse the increase of fasting blood glucose and the decrease of glucose tolerance in IR rats induced by high fat and high glucose diet.High fat and high sugar diet can lead to obvious fatty liver.After giving PS and TSG,the fatty liver was improved obviously,at the same time,histopathological findings showed that more liver cells were punctate and focal necrosis,mild fibrous tissue proliferation,and fatty degeneration induced by high fat and high sugar diet.PS and TSG also showed some improvement effects.PS and TSG could significantly reduce the increase of fasting insulin level,increase the level of glucagon and restore the abnormal blood lipid in IR state.Effects of PS and TSG on gut microecology.PS and TSG could effectively reverse the imbalance of Firmicutes / Bacteroides caused by high fat and high sugar diet.PS and TSG can significantly reduce the relative abundance of Proteobacteria in gut flora and decrease the latent potential at gate level.PS and TSG can decrease the relative abundances of Clostridium spp.,Desulfovibrio spp.and Oscillibacter spp.and thus reduce the potential pathogenic bacteria to improve gut microecology.PS and TSG can also increase the relative abundances of Bacteroides spp.and Bifidobacterium spp.,so as to improve the probiotics and relative abundance to ameliorate the gut microecology.From the functional level,the functional genes related to energy metabolism,carbohydrate metabolism,amino acid metabolism and lipid metabolism were effectively enhanced by PS and TSG,and some carbohydrate active enzyme activities were regulated.Thus regulated the homeostasis of glucose metabolism.PS and TSG also played a certain role in regulating the expressions of proteins GPR43 and p-AMPK which are involved in the body's glucose metabolism.The activations of GPR43 and p-AMPK were blocked by high fat and high sugar diet.There has been a marked improvement in this situation after giving PS and TSG.Conclusion:PS and TSG can regulate the blood glucose and improve insulin sensitivity by regulating the gut microecological diversity and its functions.PS and TSG can also regulate the expressions of GPR43 and p-AMPK which played a key role of the metabolism of glucose,ultimately improved insulin resistance.