| Corni Fructus is a Chinese traditional and famous medicine.It is the dreid,ripe,and stoneless fruit of Cornus ofcinalis Sieb.et Zucc.,it is one of the effective and traditional Chinese medicines in anti-aging and the treatment of diabetes.Currently,studies have shown that Corni Fructus has good efficacy in improving type 2 diabetes(T2DM).In this paper,the effects of different extracts of Corni Fructus to improve insulin resistance and type 2 diabetes were investigated and compared in vitro and in vivo experiments,and studying the specific mechanism of Fructus Corni improving type 2 diabetes from the perspective of inflammation.The main results and conclusions are as follows:(1)Establishment of insulin resistance model in HepG2 cells:In this experiment,HepG2 cells were used as the research object,insulin resistance model was established by high insulin induction,and through measuring glucose consumption and cell survival rate,the optimal concentration of insulin was determined to be 10-7mol/L,the best action time was 24h,and the model stabilization time was 48h.(2)Effects of different extracts of Corni Fructus and their monomers on glucose and lipid metabolism,oxidative stress and inflammation in insulin-resistant HepG2 cells:The cell viability was determined by MTT assay,and alcohol extract concentration was determined to be 200 ?g/mL,iridoid glycoside concentration was determined to be 50?g/mL,saponin concentration was determined to be 25 ?g/mL,tannin concentration was determined to be 50 ?g/mL,loganin concentration was determined to be 200 ?g/mL,morroniside concentration was determined to be 25 ?g/mL,gallic acid concentration was determined to be 5 ?g/mL,oleanolic acid concentration was determined to be 50?g/mL.All these conditions could increase glucose consumption of insulin resistant cells.In the aspect of lipid metabolism,different extracts of Corni Fructus and their monomers could reduce the content of TC,TG and lipid droplets in insulin-resistant cells.Observed under light microscope,the lipid droplets around the cells were also significantly reduced,indicating that different Corni Fructus extracts and their monomers could improve intracellular lipid metabolism disorders.The results showed that compared with the corresponding monomer group,each extract group had little difference or more obvious effect on improving lipid metabolism disorder in cells,and tannin extract and alcohol extract were most effective in improving intracellular lipid metabolism disorders.In terms of oxidative stress and inflammation,different extracts of Corni Fructus and its monomers could reduce intracellular MDA,ROS,TNF-a and IL-6 levels and increase SOD activity,indicating that Corni Fructus extract and its monomers could improve oxidative stress and inflammatory response in insulin resistant cells.The results showed that compared with the corresponding monomer group,each extract group had little difference or more obvious effect on improving the oxidative stress and inflammation in cells,and the tannin extract and alcohol extract were most effective in improving the oxidative stress and inflammation in insulin resistant cells.(3)Effects of different Corni Fructus extracts on glucose and lipid metabolism,pancreas,liver,oxidative stress and inflammation in T2DM mice:In the aspect of glucose and lipid metabolism and pancreatic pathology,different extracts of Corni Fructus could significantly reduce fasting blood glucose,insulin level,insulin resistance index,TG,TC and LDL-C levels,significantly improve glucose tolerance,increase insulin sensitivity index,insulin secretion index,and HDL-C levels.Through light microscopy,it was found that the pancreatic tissue damage in the drug-administered group was also improved.Improvements indicated that different extracts of Corni Fructus could improve the symptoms of hyperglycemia and hyperlipidemia in T2DM,relieve insulin resistance and improve pancreatic tissue damage.The results showed that tannin extract,total saponin extract and alcohol extract had the best improvement effect.In the protection of the liver,different extracts of Corni Fructus significantly reduced the levels of AST and ALT in the mice,and the liver tissue lesions showed different degrees of recovery,indicating that different extracts of Corni Fructus could improve the liver damage of type 2 diabetic mice,and the results showed that tannin extract and alcohol extract had the best effect on improving liver damage in type 2 diabetic mice.In terms of oxidative stress and inflammation,different extracts of Corni Fructus significantly reduced the levels of CRP,TNF-a,IL-6 and MDA,and significantly increased the activity of T-SOD,T-AOC and GSH-PX,indicating that different extracts of Corni Fructus could significant improve the inflammation and oxidative stress in T2DM mice,and the results showed that tannin extract and alcohol extract had the best effect on the improvement of oxidative stress and inflammation.(4)Effects of different Corni Fructus extracts on NF-?B inflammation signal pathway and insulin signaling pathway in T2DM mice:Different extracts of Corni Fructus significantly or extremely significantly down-regulated p-TAK1/TAK1,p-JNK/JNK and the expression levels of p-IKK?,NF-?Bp65,COX2,iNOS and PEPCK.The tannin extract,total saponin extract and alcohol extract significantly or extremely significantly increased the p-AKT/AKT ratio,and iridoid glycoside extracts also increased p-AKT/AKT ratio,but didn't have significant difference,tannin extract and alcohol extractl significantly or extremely significantly increased the.ratio of p-GSK3?/GSK3?,total saponin extract and iridoid glycoside extract also increased p-GSK3?/GSK3? ratio,but didn't have significant difference.It is inferred that different extracts of Corni Fructus could affect insulin signal pathway through acting on NF-?B inflammation signal pathway,improve insulin resistance,and then improve type 2 diabetes.Among them,tannin extract and alcohol extract had the most significant effect on NF-?B inflammation signaling pathway. |
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