Hizikia fusiforme has a long history of consumption and medicinal use in China. It has been found that natural plants containing polyphenol–polysaccharide complexes have better activity compared with polyphenols and polysaccharides. Therefore, in this study on enzymatic hydrolysis and fractional alcohol precipitation, two kinds of polyphenol–polysaccharide complexes (PPC), PPC1 and PPC2, were initially obtained from Hizikia fusiforme, while the dephenolization of PPC1 and PPC2 produced PPC3 and PPC4. Through in vitro assays, PPC2 and PPC4 were found to have higher antioxidant activity, and thus were selected for testing the PPCs’ anti-aging activity in a subsequent in vivo experiment with D-gal-induced aging in mice. The results indicated that PPCs could regulate the expressions of antioxidant enzymes and products of oxidation, elevate the expressions of genes and proteins related to the Nrf2 pathway in the mouse brain, enrich the gut microbiota species and increase the Bacteroidota–Firmicute (B/F) ratio. Above all, the Hizikia fusiforme polyphenol–polysaccharide complex has potential in the development of natural anti-aging drugs.

Oligosaccharides possess characteristics such as low molecular weight, good solubility, and high bioavailability, which make them better absorbed than fucoidan. This study hypothesizes that fucoidan oligosaccharides can be absorbed by intestinal epithelial cells and quickly enter the bloodstream, with a rapid absorption rate. In this study, fucoidan oligosaccharides were obtained through acid degradation and Bio Gel column separation. By analyzing the chemical composition and molecular weight, oligosaccharides with smaller molecular weights and simpler monosaccharide compositions were selected for further research. A cell model and pharmacokinetic studies in mice were established to analyze the absorption patterns of the oligosaccharides. The results showed that after acid degradation and column separation, high-molecular-weight oligosaccharides SPF1 with a molecular weight range of 1.63 × 10⁴ to 2.14 × 10⁵ Da and the low-molecular-weight oligosaccharides SPF2 with a molecular weight range of 244.22 to 1545.36 Da were obtained. In cell transport and uptake experiments, the transport of SPF1 and SPF2 was positively correlated with time and negatively correlated with concentration. The transport rates of SPF1 and SPF2 ranged from 20% to 70%, with P_app values greater than 1 × 10⁻⁵ cm/s. In the pharmacokinetics study, the blood concentration of the oligosaccharides in mice was simulated and analyzed using DAS 2.0, which indicated that the fucoidan oligosaccharides exhibited good absorption characteristics in vivo and in vitro. Therefore, fucoidan oligosaccharides with smaller molecular weights are more easily absorbed, which provides a theoretical basis for the application of fucoidan oligosaccharides.

Fucoidanase is an unstable enzyme with high specificity that requires a large about of time to screen it from microorganisms. In this study, enzymatic hydrolysis was used to produce low-molecular-weight fucoidan from microorganisms via the degradation of high-molecular-weight fucoidan without damage to the sulfate esterification structure of oligosaccharide. The microbial strain HN-25 was isolated from sea mud and was made to undergo mutagenicity under ultraviolet light. Fucoidanase was extracted via ultrasonication and its enzymatic activity was improved via optimization of the ultrasonic conditions. The enzymatic properties and degradation efficiency of fucoidanase were characterized. The microbial strain HN-25 is a Gram-negative aerobic and rod-shaped-cell bacterium, and therefore was identified as Cobetia amphilecti via 16s rDNA. The results proved that fucoidanase is a hydrolytic enzyme with a molecular weight of 35 kDa and with high activity and stability at 30 °C and pH 8.0. The activity of fucoidanase was significantly enhanced by sodium and calcium ions and inhibited by a copper ion and ethylenediaminetetraacetate (EDTA). There was a significant decrease in the molecular weight of fucoidan after enzymatic hydrolysis. The low-molecular-weight fuicodan was divided into four fractions, mainly concentrated at F3 (20~10 kDa) and F4 (≤6 kDa). These consequences suggest that fucoidanase obtained from Cobetia amphilecti is stable and efficient and could be a good tool in the production of bioactive compounds.

Ascophyllum nodosum, a brown algae abundantly found along the North Atlantic coast, is recognized for its high polysaccharide content. In this study, we investigated the anti-hyperlipidemic effect of fucoidans derived from A. nodosum, aiming to provide information for their potential application in anti-hyperlipidemic therapies and to explore comprehensive utilization of this Iceland brown seaweed. The crude fucoidan prepared from A. nodosum was separated using a diethylethanolamine column, resulting in two fucoidan fractions, AFC-1 and AFC-2. Both fractions were predominantly composed of fucose and xylose. AFC-1 exhibited a higher sulfate content of 27.8% compared to AFC-2 with 17.0%. AFC-2 was primarily sulfated at the hydroxy group of C2, whereas AFC-1 was sulfated at both the hydroxy groups of C2 and C4. To evaluate the anti-hyperlipidemic effect, a hyperlipidemia mouse model was established by feeding mice a high-fat diet. The effects of AFC-1, AFC-2, and the crude extract were investigated, with the drug atorvastatin used as a positive comparison. Among the different fucoidan fractions and doses, the high dose of AFC-2 administration demonstrated the most significant anti-hyperlipidemic effect across various aspects, including physiological parameters, blood glucose levels, lipid profile, histological analysis, and the activities of oxidative stress-related enzymes and lipoprotein-metabolism-related enzymes (p < 0.05 for the final body weight and p < 0.01 for the rest indicators, compared with the model group), and its effect is comparable to the atorvastatin administration. Furthermore, fucoidan administration resulted in a lower degree of loss in gut flora diversity compared to atorvastatin administration. These findings highlight the significant biomedical potential of fucoidans derived from A. nodosum as a promising therapeutic solution for hypolipidemia.