Study On The Hypoglycemic Activity Of Brown Seaweed Sargassum Confusum Oligosaccharides And The Related Mechanisms

Sargassum confusum C.Agardh belongs to Phaeophyta,Cyclospreae,Fucales,Sargassaceae.As a traditional Chinese medicine,S.confusum has a variety of biological activities,such as hypoglycemic,hypolipidemic,anti-tumor and so on.The purpose of the present study was to investigate the antidiabetic activity of S.confusum oligosaccharides(SCO)that were obtained by enzymatic hydrolysis of polysaccharides.This research provide possible evidence for the hypoglycemic activities effects of SCO which may be used as adjuvant therapy and functional food to control blood glucose.The polysaccharides were extracted from S.Confusum,and SCO were prepared by hydrolyzing polysaccharides and the structures were identified.The results showed that the highest yield of SCO was 5.76±0.30%,which was gave under the optimal conditions for enzymatic hydrolysis at pH 6 and 51? for 4 h.The results of the structure identification showed that the SCO as ?-pyran structure contained carbonyl group and acarboxyl group,which may be the presence of uronic acid.SCO consisted of fucose,arabinose,xylose and glucose.Effects of SCO on ?-glucosidase activity and glucose metabolism in insulin-resistance human hepatocellular carcinoma(IR-HepG2)cells were evaluated in vitro.SCO showed strong inhibitory activity against?-glucosidase with an IC50 value of 9.9 mg/mL.SCO had no negative influence on the viability of HepG2 cells.Compared with model group,the glucose consumption of IR-HepG2 cells were significantly promoted by 75.3%at 200?g/mL of SCO(p<0.01),which indicated that SCO could improve the glucose consumption and may ameliorate the insulin resistance in IR-HepG2 cells.The hypoglycemic activities of SCO in high-fat/high-sucrose fed golden hamsters was conducted in vivo.The results showed treatment of high fat fed hamsters with SCO in the dose of 150 mg/kg for 60 days significantly decrease the level of bady weight,alanine transaminase,aspartate transaminase and triglyceride compared with model group(p<0.05),and maintain the fasting blood glucose level,fasting serum insulin,total cholesterol level within the normal range.Furthermore,SCO treatments efficiently ameliorated lipids accumulation in hepatocytes.The analysis of gut microbiota indicated that at the Phylum level,in the model group,the number of Firmicutes bacteria was increased significantly while Bacteroidetes bacteria was significantly reduced,which was associated with an increase in dietary energy absorption and a low level of inflammation.The composition of gut microbiota in SCO-treatment group was generally similar to that in normal group.Specifically,the Lactobacillus and Bifidobacterium increased significantly in SCO-treatment group compared to model group,and Parabacteroides populations was significantly decreased by SCO treatment.The mRNA and protein expressions of phosphatidylinositol 3-kinase(PI3K),insulin receptor substrate 1(IRS1),c-jun N-terminal kinase 1 and 2(JNK1/2),glucose transporter-4(GLUT4)were examined to explore the hypoglycemic mechanism of SCO.qPCR assays indicated the mRNA expression of PI3K and IRS1 were increased significantly and JNK1/2 were decreased in the SCO-treatment group compared with high fat fed hamsters(p<0.05).Western blot assays showed SCO could up-regulate the PI3K and IRS1 protein expressions(p<0.05)and down-regulate the JNK1/2 protein expressions(p<0.05).These results suggest that SCO could regulate the insulin PI3K/JNK signaling pathway to ameliorate cells insulin status,thus promote the glucose consumption.