Phenyl Caffeate In Propolis Improves Insulin Resistance Based On JNK And NF-?B Inflammatory Pathways

Diabetic population of China is the most in the word.The population of type 2 diabetes mellitus(T2DM)is 90%of diabetic population.Searching for a natural product to improve T2DM is an important trend.We chose a natural product-propolis,as our object of study to investigate the effect of propolis on improving glucolipid metabolism based on inflammatory pathway.We found out the results as follows:(1)The active compounds in propolis in Changbai Mountain were the highest by comparing the contents of propolis flavones and phenolic acids in three propolis producing areas in China.The total content of flavonoids wass 56.85±1.21 mg/g,and the total content of phenolic acids was 44.25±0.06 mg/g.Galangin(28.38±1.52 mg/g),chrysin(24.73±2.10 mg/g)and caffeic acid phenethyl ester(CAPE,37.96±0.14 mg/g)were three highest content compounds in propolis.(2)The content of tau-fluvalinate residues was 1.1 ±0.01 mg/kg,which exceeded the highest standard in agricultural standards,while other acaricides could not be detected.The content of a-666 was 0.043±0.003 mg/kg in propolis,while other organo-chlorine pesticide could not be detected.The content of lead was 0.046±0.002 mg/kg,and the content of arsenic was 0.038±0.001 mg/kg,which did not exceed the standard.(3)In the three active compounds of propolis,the HMG-CoA reductase model screened out that CAPE had the strongest ability to inhibit HMG-CoA reductase,and the inhibition rate was 34.31±1.61%.It is strongest that the ability of CAPE to inhibit the the expression of glucose-6-phosphatase(G6Pase)mRNA.It is suggested that CAPE in propolis is the best active compound in propolis to improve the effect of glycolipid metabolic disorder.(4)We used high glucose and palmitic acid to induce HepG2 cells to establish insulin resistance model cells.In the insulin resistance cells,it showed that CAPE improved the glucose consumption and absorptive capacity of cells.It increased glycogen synthesis and reduced the expression of glucose-6-phosphatase and oxidative stress ROS.CAPE could also inhibit JNK and NF-?B signaling pathway.The results above demonstrated that CAPE improved insulin resistance through the inflammatory signaling pathway of JNK and NF-?B,in vitro.(5)C57BL/6J mice were induced by high-fat diet and streptozotocin(STZ)to become T2DM model mice.In the T2DM model mice,it showed that CAPE ameliorated weight growth and food intake of mice,and reduced the HOMA-IR index,TC,TG,LDL-c,but increased HDL-c level and PPAR-a levels in mice.Pro-inflammatory cytokines(TNF-?,IL-6,and MCP-1)in serum and the expressions of TNF-? mRNA in tissues were markedly down-regulated from CAPE-treated mice.CAPE could also inhibit JNK and NF-?B signaling pathway.In summary,CAPE could improve insulin resistance through modulation of JNK and NF-?B signaling pathway in mice.