The Anti-diabetic Effects And Mechanisms Of Polysaccharides From Sargassum Fusiforme

Diabetes mellitus is a metabolic disease characterized by chronic hyperglycemia,and its prevalence and mortality are constantly increasing in recent decades.Though lots of drugs have been applied to DM treatment,most of them have side effects like ketoacidosis,hypoglycemia,gastrointestinal reactions,heart failure,etc..Therefore,developing novel non-toxic bioactive ingredient and exploring its hypoglycemic mechanisms are particularly important for the prevention and treatment of type 2 diabetes(T2DM).Sargassum fusiforme,an edible economic seaweed,is widely distributed in the southeast coastal area of China and has been cultivated on a large scale in Zhejiang Province.Sargassum fusiforme has many biological activities like antioxidation,anti-tumor,anti-virus,hypoglycemic effects,etc.,polysaccharide is the main bioactive component of Sargassum fusiforme and plays an important role in these above bioactive functions.Previously,we compared the yield and α-glucosidase inhibitory activity of Sargassum fusiforme polysaccharides with different extraction methods.Our results indicated that Sargassum fusiforme polysaccharide,extracted by enzyme-ultrasound-assisted hot water,possessed the highest yield and α-glucosidase inhibitory activity.Therefore,in this study,the crude Sargassum fusiforme polysaccharide(SFP)was prepared by the enzyme-ultrasoundassisted hot water extraction,and two different molecular weight Sargassum fusiforme polysaccharides fractions(SFP-1,Mw < 10 k Da)and SFP-2(Mw > 10 k Da)were separated by ultrafiltration,SFP,SFP-1 and SFP-2 were collectively named as SFPs.The structure and hypoglycemic activities of SFPs were firstly studied.Besides,the anti-diabetic effects and molecular mechanisms of SFPs in high-sugar and high-fat diet and streptozotocin(STZ)induced rats were further explored.The main contents and results were listed as follows:(1)A comparative study on the chemical composition,structural characteristics and hypoglycemic activities of SFPs was conducted.Results indicated that SFP-2 had the highest total sugar(83.51 ± 4.39%)and uronic acid content(37.99 ± 0.95%),while SFP-1 had the highest sulfuric acid group content(9.57 ± 0.69%),and the contents of total phenols and protein in SFPs were less than 1%;SFPs were all composed of fucose,mannose,rhamnose,glucose,galactose and glucuronic acid,but their monosaccharide composition ratio were different.The results of hypoglycemic activity demonstrated that SFP,SFP-1 and SFP-2 could delay glucose dialysis in vitro and reduce the postprandial blood glucose fluctuation in normal rats after starch loading.Particularly,SFP-2 performed better effect in regulating postprandial blood glucose fluctuation than SFP and SFP-1(2)The improvement effects of SFPs on T2 DM rats induced by high-sugar and high-fat diet and STZ was deeply investigated.The results indicated that SFPs treatment could improve body weight loss and glucose tolerance,reduce fasting blood glucose,insulin resistance index and blood lipid levels,increase hepatic glycogen content,and ameliorate liver and kidney inury in T2 DM rats.Importly,the improvement effects of SFP and SFP-2 in controlling fasting blood glucose were better than SFP-1.In addition,SFP-2 performed better effects in the improvement of insulin resistance and hyperlipidemia,as well as the promotion of hepatic glycogen synthesis as compared to SFP and SFP-1.Besides,SFPs treatments could effectively improve the composition of the gut microbiota in T2 DM rats.At phylum level,SFPs treatments could elavate the abundances of Firmicutes and Bacteroidetes,while reduce the abundance of Proteobacteria.At the genus level,after 8-week SFPs treatment,the relative abundance of Escherichia-Shigella was significantly reduced,while the abundances of Muribaculaceae＿norank,Lachnospiraceae,Ruminococcus＿1 and Romboutsia were significantly increased.Additionally,SFP-2 supplementation for 8 weeks also significantly elevated the abundances of Bifidobacterium,Lactobacillus,Akkermansia and Faecalibaculum.(3)The molecular mechanisms of SFPs in improving T2 DM was further explored by RTqPCR.The results indicated that SFPs intervention could activate the expression of IRS-1,IRS-2 and Akt,and inhibit the expression of GSK-3β.Specially,SFP-2 had better regulatory on the expression of GSK-3β when compared to SFP and SFP-2.Additionally,SFP-2 could significantly elevate the expression level of Ins R,SFP and SFP-2 could significantly increase the expression level of PI3 K and GLUT2.All of these manfisted that SFP-2 could promote glycogen synthesis via Ins R/IRS/PI3K/Akt/GLUT/GSK-3β signalling pathway.In addition,SFP and SFP-2 could inhibit liver gluconeogenesis via inhibiting the expressions of PEPCK and G-6-Pase in the liver of T2 DM rats.Futhermore,SFP-1 and SFP-2 could inhibit the expressions of SREBP-1c and ACC,and the expressions of SREBP-1c in the rats of SFP-2group were lower than SFP-1.