Hypoglycemia Effect And The Mechanism Of Mixture Of Apostichopus Japonicus And Cordyceps Militaris

Sea cucumber belongs to the Holothuroidea in biological classification and is distributed throughout the world seas. It has been a traditional tonic food in China and other Asian countries due to its antitumor, immunoregulatory, antiatherosclerotic, and anti-aging properties. Nowadays, many studies show that the body wall of sea cucumber contains many bioactive substances, such as polysaccharides, collagen, triterpene glycosides and so on, which exhibit excellent effect of immunomodulatory, anti-oxidation, anti-tumor, and anti-hypertension. Cordyceps militaris is known as the Chinese rare caterpillar fungus, and it has been listed as a new source food in China since 2008. Its chemical components, including cordycepin, D-mannitol, and various polysaccharides are similar to the substances contained in famous Chinese traditional medicine C. sinensis. The efficacy of C. militaris was confirmed in the treatment of cardiovascular and renal dysfunction, in immune enhancement and in the anti-hyperlipidemia effect. Use the mixture of sea cucumber and C. militaris may enhance the effect on some diseases.The aim of this study is to investigate the hypoglycemia effect of the mixture of Apostichopus japonicas and C. sinensis on diabetic rats, which were established by intraperitoneal injection of streptozotocin (STZ), and to discuss the mechanism involved in this effect. The major results are as follows:The mixture exhibit a significant hypoglycemia effect on STZ-induced diabetic rats. With mixture treated 35 days, a dramatic decrease in fasting blood level was observed in both low and high dosage groups (P<0.01), and the glucose tolerance was improved. The mixture can increase serum insulin contents (P<0.01), insulin secretion index (P<0.01) andβ-cell function index (P<0.01); moreover, it can improve the contents of muscle glycogen and liver glycogen notably (P<0.01). Meanwhile, the contents of glycosylated hemoglobin and glycosylated serum protein were significantly decreased by this mixture (P<0.05, P<0.01). These results suggested that the mixture of A. japonicus and C. militaris could improve the glucose metabolism level and have a better hypoglycemic effect on diabetic rats, and the effect in mixture groups are more better than that in A. japonicas or C. militaris.The mixture can prevent the damage of oxidation stress by enhance the ability of antioxidation. The results showed that the antioxidase activities of Superoxide Dismutase (SOD), Catalase (CAT) and Glutathione Peroxidase (GSH-Px) in liver were improved obviously in both low and high dosage groups (P<0.01). The mixture can also increase the activity of CAT in pancreas (P<0.01). The protect effect of the mixture on islet of diabetic rats was observed using the method of hematoxylin-eosin stain and transmission electron microscope. In the groups treated with the mixture, the number ofβcells of islet was increased in comparision to the model group, and the degree of oxidation damage was reverted to a normal level. The observation of transmission electron microscope showed that, the nucleus architecture in mixture group are remarkably reverted to a normal status, and the membrane of nucleus was smooth, nucleolus and chromatins were clear. Only a slightly swelling in mitochondrion and granular endoplasmic was observed in the group of the mixture. All the results indicated that mixture of A. japonicas and C.militaris can enhance the ability of anti-oxidation of the body and the pancreas to protect theβcells, keep the normal morphology of cells, and improve the function of synthesis and secret insulin.The investigation of hypoglycemia mechanisms of the mixture were conducted by RT-PCR and Western Blot. The mRNA and protein expression levels of phosphatidylinositol 3-kinase (PI3K), serine-threonine kinases (Akt) and glucose transporter 4 (Glut4) in skeletal muscle and adipose tissues were examined. The results implied that this mixture could significantly increase the mRNA expressions of PI3K and Glut4 in skeletal muscle (P<0.01). In adipose tissues, PI3K expression levels of high dosage group was increased by 42.86%, and that of Glut4 in low and high group was average increased by 32.63% (P<0.05, P<0.01). The protein expression levels of Glut4 were also enhanced by the mixture in adipose tissue of low and high dosage group (P<0.01) and there exist a dosage-dependent relationship. Results suggest that the mixture of A. japonicas and C. militaris exhibits significant hypoglycemia activity through improvement of insulin signaling pathway by which enhance the glucose uptake and utilization in peripheral tissues and finally decreased the high glucose level in blood.In conclusion, the hypoglycemia effect of the mixture of A. japonicas and C. militaris may be related to its antioxidant bioactivity, and the mixture can upregulat the gene and protein expression of key protein kinases and Glut4 in skeletal muscle and adipose tissues, that may be one of the most important mechanism involved in this effect.