Preparation Of Two Sea Cucumber Polysaccharide Fractions And Their Ameliorative Effects On Type 2 Diabetes In Rats

Low-edible-value sea cucumbers all over the world are rich in active polysaccharides,being potential resources for antidiabetic polysaccharides and important breakthrough for commercialization of sea cucumber polysaccharides.The present study aimed at comparatively evaluating extraction yields and structure characteristics of polysaccharide fractions extracted from 10 low-edible-value sea cucumber species selected from global commercial sea cucumber species,screening sulfated fucan-dominated and fucosylated chondroitin sulfate-dominated polysaccharide fractions,and comparatively investigating preventive and therapeutic effects of sulfated fucan-dominated and fucosylated chondroitin sulfate-dominated polysaccharide fractions on T2DM and its complication using a high-fat diet(HFD)and streptozotocin(STZ)-induced T2DM rat model.The results were helpful for providing a promising strategy to extract antidiabetic polysaccharides from low-edible-value sea cucumber species as alternatives to high-edible-value sea cucumber-derived polysaccharides for functional foods to ameliorate T2DM.The main research contents and conclusions were as listed follows:(1)Ten polysaccharide fractions of low-edible-value sea cucumber species were prepared by soaking,crushing,enzymatic hydrolysis,heating,ultrafiltration,deproteinization and ethanol precipitation.The extraction yields of polysaccharide fractions ranged from 3.90% to 11.44%.The high extraction yields were observed for the polysaccharide fractions from Stichopus choloronotus,Thelenota ananas,and Cucumaria frondosa,while the lowest extraction yield was observed for Holothuria impatiens polysaccharide fraction.The sulfate contents of polysaccharide fractions ranged from 8.06 % to 13.15 %.The highest sulfate content was observed for Thelenota ananas polysaccharide fraction and the lowest sulfate contents were observed for polysaccharide fractions from Cucumaria frondosa and Ypsilothuria bitentaculata.Polysaccharide fractions from Thelenota ananas,Stichopus variegatus,Stichopus choloronotus and Holothuria nobilis possessing high proportions of linear macromolecules had similar monosaccharide compositions.Polysaccharide fractions from Holothuria albiventer and Holothuria scabra possessing a small amount of linear macromolecules had similar monosaccharide compositions.Polysaccharide fractions from Holothuria tubulosa and Ypsilothuria bitentaculata having similar monosaccharide compositions possessed more branched components.Polysaccharide fraction from Holothuria impatiens possessing a small amount of linear macromolecules had highest proportions of N-acetyl-D-galactosamine(Gal NAc).Thelenota ananas polysaccharide fraction possessing the highest proportion of fucose and largest amounts of linear macromolecules was identified as sulfated fucan-dominated polysaccharide fraction.Cucumaria frondosa polysaccharide fraction exhibiting the lowest proportion of fucose,highest proportion of glucose and the largest amounts of highly branched components was identified as fucosylated chondroitin sulfate-dominated polysaccharide fraction.There were residual proteins/peptides in these polysaccharide fractions.A total of 21 DPP-4 inhibitory peptides(including 19 dipeptides and 2 tripeptides)were detected in simulated gastrointestinal digests of these polysaccharide fractions.The digest of Cucumaria frondosa polysaccharide fraction was rich in a variety of DPP-4 inhibitory peptides,especially 9 DPP-4 inhibitory peptides including VV,SL(I),L(I)V,L(I)T,L(I)L(I),EV,TF,YL(I)and L(I)PL(I)with low contents in digests of 9 remaining sea cucumber polysaccharide fractions.(2)There were commonalities in the prevention and treatment of T2DM and its complications between sulfated fucan-dominated polysaccharide fraction from Thelenota ananas and fucosylated chondroitin sulfate-dominated polysaccharide fraction from Cucumaria frondosa as follows: for two intervention approaches,two polysaccharide fractions improved glucose tolerance and insulin resistance,decreased inflammatory status and oxidative stress,restored hypertriglyceridemia and hypercholesterolemia,protected against liver injury,and promoted accumulation of hepatic glycogen by activating IRS/PI3K/AKT signaling,ameliorated hyperglycemia and the symptoms of polyphagia in HFD-STZ induced T2DM rats.Two polysaccharide fractions exhibited better preventive effects at low dose.The therapeutic effects of two polysaccharide fractions were better than the preventive effects,which were comparable to that of the first-line clinical drug(metformin).The polysaccharide fractions from Thelenota ananas and Cucumaria frondosa were good alternatives to high-edible-value sea cucumber-derived sulfated fucan/fucosylated chondroitin sulfate for functional foods to ameliorate T2DM.(3)There were differences in the prevention and treatment of T2DM and its complications between sulfated fucan-dominated polysaccharide fraction from Thelenota ananas and fucosylated chondroitin sulfate-dominated polysaccharide fraction from Cucumaria frondosa as follows: for preventive approach,Cucumaria frondosa polysaccharide fraction was good at regulating fasting blood glucose,inflammation and insulin secretion in T2DM rats,while Thelenota ananas polysaccharide fraction was good at improving the symptoms of polyphagia,hepatomegaly and dyslipidemia.There were also differences in the targets for the same polysaccharide fraction at different doses to treat T2DM and its complications.For therapeutic approach,Cucumaria frondosa polysaccharide fraction was better than the Thelenota ananas polysaccharide fraction in the treatment of T2DM and its complications.Cucumaria frondosa polysaccharide fraction was good at improving the symptoms of polyphagia,dyslipidemia,kidney function and hepatic glycogen synthesis in T2DM rats.Thelenota ananas polysaccharide fraction did not exhibit specific therapeutic advantages.The same sea cucumber polysaccharide fraction at different doses had different ways in the treatment of T2DM and its complications.