Research progress on extraction, chemical modification, hypoglycemic activity and mechanism of fucoidan
Fucoidans (FU) are mainly derived from marine brown algae such as fucoidan, seaweed, horsetail algae, and marine invertebrates such as sea cucumber and sea urchin. They are complex sulfated polysaccharides, also known as fucoidan sulfates. The monosaccharide composition of FU is mainly fucose, with small amounts of galactose, xylose, rhamnose, mannose, arabinose, glucuronic acid, and a large number of sulfate groups. It is a polyanionic homotype heteropolysaccharide. There are two types of FUs skeleton: type I chain or type II chain (see Figure 1). Type I chain contains repeated (1 → 3) – α – L-pyranose fucose, while type II chain contains alternating (1 → 3) and (1 → 4) – linked α – L-pyranose fucose, with monosaccharides connected by α -1,2, α -1,3, or α -1,4-glycosidic bonds.
FU has a wide range of health benefits and therapeutic effects, including anti-tumor, anti oxidative, anti fatigue, immune regulation, antibacterial, anti liver injury, lipid-lowering, antithrombotic, anti-inflammatory, anti angiogenic, anticoagulant, hypoglycemic, anti allergic, anti radiation, and promoting wound healing; In addition, FU also has the potential role of anti novel coronavirus, which has attracted more and more attention. The chemical composition and structure of FU vary significantly due to differences in geographical location, species, season, and extraction techniques. Its molecular weight and sulfate content have a significant impact on its functional activity, and chemical modification can further improve its functional activity. Therefore, this article focuses on summarizing the extraction methods, chemical modification, and hypoglycemic activity and mechanism of FU, exploring future research directions in the extraction and chemical modification of FU, and delving into the structure-activity relationship between FU structure and hypoglycemic and other biological activities, which is also a future research focus. This article can provide new ideas for the preparation of FU, which is helpful for the effective utilization of natural and modified FU, and provide reference for the development of FU hypoglycemic functional foods and health products.

The traditional extraction method for FU has a generally low yield, and the yield is also affected by different extraction methods and conditions. Therefore, further research is needed on extraction methods with higher yields. According to current literature reports, the subcritical water extraction method has the highest yield, with a FU yield of 13.56%. The extraction method has a significant impact on the structure of FU, therefore, in the actual extraction process, different extraction methods can be adopted according to the needs. For example, to preserve the complete FU structure, a mild extraction method is required to prevent the FU molecular chain from being cleaved.

Carboxymethylation can increase the solubility and electronegativity of polysaccharides, enhance their biological activity, and even generate new biological activities. In recent years, there has been an increasing amount of research on the carboxymethylation of polysaccharides. Carboxymethylated polysaccharides have outstanding biological activities in anti-tumor, antioxidant, and immune regulation. There have been many studies on the methylation/carboxymethylation, graft copolymerization, and esterification of alginates. However, there have been no reports on the methylation/carboxymethylation and graft copolymerization of FU, and its esterification reaction has not been widely studied. Therefore, methods such as carboxymethylation modification and esterification are new research directions for FU modification in the future.

Sulfated polysaccharides can interact with proteins at pH values above their isoelectric point, exhibiting good affinity for proteins. The negatively charged FU binds to the partially positively charged protein (antithrombin) through electrostatic interactions. The electrostatic interactions between FU and some positively charged amino acids on alpha amylase can change its conformation. Therefore, the electrostatic interactions between the negatively charged sulfate groups of FU and alpha amylase may participate in the regulation of alpha amylase activity, thereby changing its catalytic ability. The sulfate groups in fucoidan are inevitably related to their inhibition of alpha amylase activity. However, the exact site of this electrostatic interaction and the mechanism by which the sulfate group in FU inhibits alpha amylase activity are still unclear. The existing physical and chemical methods cannot fully describe a certain polysaccharide structure and the relationship between polysaccharide structure and hypoglycemic activity. The function of FU is closely related to its structure, and currently there is a lack of research on the molecular structure of FU. The position of most monosaccharides in the polysaccharide main chain of FU is not yet clear. Currently, most research on FU focuses on the analysis of the functional group content related to its structure, and there is relatively little research on the higher-level structure and spatial conformation of FU. In the future, further attention and exploration are needed in these areas, so the focus of future research will be on the grading and isolation of FU bioactive components to determine their structure and relationship with hypoglycemic and other various biological activities.