The therapeutic potential of natural bioactive compounds such as polysaccharides, especially glycosaminoglycans, is now well documented, and this activity combined with natural biodiversity will allow the development of a new generation of therapeutics. Advances in our understanding of the biosynthesis, structure and function of complex glycans from mammalian origin have shown the crucial role of this class of molecules to modulate disease processes and the importance of a deeper knowledge of structure-activity relationships. Marine environment offers a tremendous biodiversity and original polysaccharides have been discovered presenting a great chemical diversity that is largely species specific. The study of the biological properties of the polysaccharides from marine eukaryotes and marine prokaryotes revealed that the polysaccharides from the marine environment could provide a valid alternative to traditional polysaccharides such as glycosaminoglycans. Marine polysaccharides present a real potential for natural product drug discovery and for the delivery of new marine derived products for therapeutic applications.
Water-soluble sulfated polysaccharides isolated from two red algae Sphaerococcus coronopifolius (Gigartinales, Sphaerococcaceae) and Boergeseniella thuyoides (Ceramiales, Rhodomelaceae) collected on the coast of Morocco inhibited in vitro replication of the Human Immunodeficiency Virus (HIV) at 12.5 µg/mL. In addition, polysaccharides were capable of inhibiting the in vitro replication of Herpes simplex virus type 1 (HSV-1) on Vero cells values of EC50 of 4.1 and 17.2 µg/mL, respectively. The adsorption step of HSV-1 to the host cell seems to be the specific target for polysaccharide action. While for HIV-1, these results suggest a direct inhibitory effect on HIV-1 replication by controlling the appearance of the new generations of virus and potential virucidal effect. The polysaccharides from S. coronopifolius (PSC) and B. thuyoides (PBT) were composed of galactose, 3,6-anhydrogalactose, uronics acids, sulfate in ratios of 33.1, 11.0, 7.7 and 24.0% (w/w) and 25.4, 16.0, 3.2, 7.6% (w/w), respectively.
The therapeutic potential of low-molecular-weight (LMW) fucoidan, a sulfated polysaccharide extracted from brown seaweed devoid of direct antithrombin effect, was investigated in vitro and in a model of critical hindlimb ischemia in rat. In vitro results showed that LMW fucoidan enhanced fibroblast growth factor (FGF)-2-induced [3H]thymidine incorporation in cultured rat smooth muscle cells. Intravenous injection in rats of LMW fucoidan significantly increased the stromal-derived factor (SDF)-1 level from 1.2 ± 0.1 to 6.5 ± 0.35 ng/ml in plasma. The therapeutic effect of LMW fucoidan (5 mg/kg/day), FGF-2 (1 μg/kg/day), and LMW fucoidan combined with FGF-2 was assessed 14 days after induction of ischemia by 1) clinical evaluation of claudication, 2) tissue blood flow analysis, 3) histoenzymology of muscle metabolic activity, and 4) quantification of capillary density. Both LMW fucoidan and FGF-2 similarly improved residual muscle blood flow (62.5 ± 6.5 and 64.5 ± 4.5%, respectively) compared with the control group (42 ± 3.5%, p < 0.0001). The combination of FGF-2 and LMW fucoidan showed further significant improvement in tissue blood flow (90.5 ± 3%, p < 0.0001). These results were confirmed by phosphorylase activity, showing muscle regeneration in rats treated with the combination of FGF-2 and LMW fucoidan. Capillary density count increased from 9.6 ± 0.7 capillaries/muscle section in untreated ischemic controls to 14.3 ± 0.9 with LMW fucoidan, 14.5 ± 0.9 with FGF-2, and 19.1 ± 0.9 in combination (p < 0.001). Thus, LMW fucoidan potentiates FGF-2 activity, mobilizes SDF-1, and facilitates angiogenesis in a rat model. This natural compound could be of interest as an alternative for conventional treatment in critical ischemia.