Preparation And Biological Activities Of κ-Carrageenan Oligosaccharides And Their Derivatives

In recent years, the chemical modification of marine polysaccharides, which lead to preparation of derivatives with high biological activities and/or low toxicity, has attracted more and more attention. Carrageenan is a collective term for a group of sulfated polysaccharides extracted from marine red algae and its biological activities were widely studied. However, there are very few reports in the literature on the biological activities of sulfated oligosaccharide. In this study, carrageenan polysaccharide was degraded by mild acidic hydrolysis and the oligosaccharides and their oversulfated, acetylated and phosphorylated derivatives were prepared and their structures were elucidated and their antioxidant and antitumor activities were investigated. In order to study the relationship between chemical characteristic and biological activity, kappa-carrageenan oligosaccharides were prepared through mild hydrochloric acid hydrolysis of polysaccharides. Oligosaccharide fractions were isolated by gel permeation chromatography and the structure of fraction 1 (F1) was studied by using negative-ion electrospray ionization-mass spectrometry (ESI-MS), and 1H and 13C-NMR spectrometry. The in vitro antitumor effects in three human neoplastic cell lines (KB, BGC, and Hela) of polysaccharides and F1 were investigated. The bioassay results showed that F1 exhibited relatively higher antitumor activity against the three cancer cells than polysaccharides. Crude oligosaccharides prepared through mild hydrochloric acid hydrolysis of polysaccharides were used as starting polymers for the partial synthesis of their oversulfated, acetylated and phosphorylated derivatives. The structure and the substitution pattern of oligosaccharides and their derivatives were studied by using FT-IR and 13C NMR spectroscopy. Antioxidant activity of κ-carrageenan oligosaccharides and their chemical modification derivatives was investigated employing various established in vitro systems, such as superoxide, hydroxyl and DPPH radicals scavenging, reducing power, iron ion chelation and total antioxidant activity using β-carotene-linoleic acid system. The oversulfated (SD), lowly (LAD) and highly acetylated derivatives (HAD) in scavenging superoxide radicals and in reducing power assay, the phosphorylated (PD) and lowly acetylated derivatives in scavenging hydroxyl radicals, the phosphorylated derivative in scavenging DPPH radical and in metal chelating assay, and oversulfated and phosphorylated derivatives total antioxidant activity assay exhibited stronger free radical scavenging and higher antioxidant activity than carrageenan oligosaccharides. The results indicated that the chemical modification of carrageenan oligosaccharides can enhance their antioxidant activity. Following that, the intracellular antioxidant ability and protective effects of carrageenan oligosaccharides and their derivatives on hydrogen peroxide and long-wave ultraviolet radiation induced oxidative damage were investigated by using the MTT tetrazolium assay in mouse thymic lymphocyte. All the carrageenan oligosaccharides and their derivatives showed the significant antioxidant activity compared to the control. Inhibitory effects of carrageenan oligosaccharides and their derivatives against transplanted S180 and H22 tumor in mice were also evaluated. Carrageenan oligosaccharides and their derivatives can significantly inhibit the growth of S180 and H22 in mice. At the same time, they can increase the index of spleen especially thymus in transplanted S180 and H22 tumor mice, which indicated their immunomodulation activity.