Structure And Bioactivity Analysis Of Fucosylated Chondrointin Sulfate From Pearsonothuria Graeffei And Its Oligosaccharides

In this paper we used sea cucumber Pearsonothuria graeffei as the raw material, obtaining a novel fucosylated chondroitin sulfate (fCS-Pg). A novel method for degradating the sea cucumber fucosylated chondroitin sulfate (SC-fCS) was developed to make up for existing problems in current degradation methods. The oligosaccharides degraded via the new method not only possessed significant anticoagulant activity, but also had less side effects. The structure of fCS-Pg was also confirmed through detailed analysis. Besides, the anti-hyperlipidemic activities of fucosylated chondroitin sulfate from sea cucumber Isostichopus badionotus (fCS-Ib) and fCS-Pg were compared and their anti-hyperlipidemic mechanism was studied. The details are as follows:1. A method for depolymerization of a novel fCS-Pg using60Co γ ray irradiation in water solution was developed in the current study. Fragments with varying molecular weights were obtained by60Co y ray irradiation at different dosages and sample concentrations. The chemical compositions and structures of these fragments were further investigated using high-performance liquid chromatography (HPLC), infrared spectroscopy (IR) and nuclear magnetic resonance spectroscopy (NMR). The results indicated that60Coy ray irradiation induced depolymerization via selective breakage of glucuronic acid (GlcA) units in the fCS-Pg backbone, without significant influence on sulfated fucose branches under mild conditions. The optimal conditions to degrade fCS-Pg were2-10%solution concentration and irradiation dosages of10-50kGy. fCS-Pg was identified to be a CSE backbone with Fuc3,4S and Fuc2,4S.2. The anticoagulant activities in vitro of fCS-Pg oligasaccharides degraded under different irradiation conditions were evaluated. The results suggested that fCS-Pg oligasaccharides displayed significantly decreased anticoagulant activities compared to the native fCS-Pg and anticoagulant activities were reduced with decreasing molecular weights. Based on the collective findings, we propose that these fragments are potentially applicable as antithrombotic agents with reduced bleeding risk relative to native fCS-Pg.3. The anti-hyperlipidemic effects of fCS-Ib and fCS-Pg were compared using a preventative hyperlipidemic animal model. The results indicated the two SC-fCSs could significantly lower the serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) levels, and increase the high density lipoprotein cholesterol (HDL-C) level. They could also reduce liver weights, glutamic pyruvic transaminase (GPT) and glutamic oxaloacetic transaminase (GOT) activities compared to the hyperlipidemia group. What’s more, they could improve impaired glucose tolerance and the anomal hepatic glycogen. The difference between them was that fCS-Ib showed better effect on improving the serum TG and hepative glycogen level while fCS-Pg had better effect on protecting livers. Our results indicated fCS-Ib and fCS-Pg could be potential anti-hyperlipidemic drug with protecting effect on the liver damage and the fCS-Ib showed better anti-hyperlipidemic and anti-hyperglycemic activities.