Sulfation pattern of fucose branches affects the anti-hyperlipidemic activities of fucosylated chondroitin sulfate

Abstract

Fucosylated chondroitin sulfates (fCSs) are glycosaminoglycans extracted from sea cucumbers, consisting of chondroitin sulfate E (CSE) backbones and sulfated fucose branches. The biological properties of fCSs could be affected by the sulfation pattern of their fucose branches. In the present study, two fCSs were isolated from sea cucumbers Isostichopus badionotus (fCS-Ib) and Pearsonothuria graeffei (fCS-Pg). Their monosaccharide compositions of glucuronic acid (GlcA), N-acetylgalactosamine (GalNAc), fucose (Fuc) and sulfate were at similar molar ratio with 1.0/0.7/0.9/3.1 for fCS-Ib and 1.0/0.8/1.5/2.6 for fCS-Pg. The two fCSs have different sulfation patterns on their fucose branches, fCS-Pg with 3,4-O-disulfation while fCS-Ib with 2,4-O-disulfation. Their antihyperlipidemic effects were compared using a high-fat high-fructose diet (HFFD)-fed C57BL/6J mice model. Both fCS-Ib and fCS-Pg had significant effects on lipid profile improvement, liver protection, blood glucose diminution and hepatic glycogen synthesis. Specifically, fCS-Pg with 3,4-O-disulfation fucose branches was more effective in reduction of blood cholesterol (TC), low density lipoprotein (LDL) and atherogenic index (AI). Our results indicate that both fCSs, especially fCS-Pg, could be used as a potential anti-hyperlipidemic drug.

Pharmacological Potential of Sea Cucumbers

“…Certain structural patterns provide potency to the lipid lowering activity of marine glycosaminoglycan. For instance, glycosaminoglycan with 3,4- O -disulfation fucose branches exert more pronounced lowering of blood lipid level than glycosaminoglycan with 2,4- O -disulfation [ 149 ]. These data suggest that FuCS from various sea cucumber species maybe successfully used in the prevention and treatment of obesity, atherosclerosis and their complications.…”

Structural characterization and hypolipidemic activities of purified stigma maydis polysaccharides

“…Nowadays, statins and fibrates are the well‐known hypolipidemic drugs that are used to prevent cardiovascular diseases. However, these currently used hypolipidemic drugs often trigger several adverse effects such as hyperuricemia, peripheral neuropathy, memory loss, muscle damage, and skin rashes (Wu et al, ), especially in a long‐term treatment. Therefore, it is imperative to develop a safe and effective alternative for the treatment of hypolipidemic.…”

Current Research Landscape of Marine-Derived Anti-Atherosclerotic Substances

“…In previous studies, chondroitin sulfate A decreases the lipid levels of serum and aortic in monkeys fed with a high-fat diet [103]. In addition, fucosylated CS extracted from sea cucumbers improves lipid profile, in which fucosylated CS with 3,4-O-disulfate fucose branches are much more effective in improving blood lipid and atherosclerosis index and could be potential in hypolipidemic treatment [104].…”