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Marine macroalgae are efficient producers of sulfated polysaccharides. The algal sulfated polysaccharides possess diverse bioactivities and peculiar chemical structures, and represent a great potential source to be explored. In the present study, a heparinoid-active sulfated polysaccharide was isolated from the green alga Cladophora oligoclada. Results of chemical and spectroscopic analyses indicated that the sulfated polysaccharide was composed of →6)-β-d-Galp-(1→, β-d-Galp-(1→, →6)-α-d-Glcp-(1→ and →3)-β-d-Galp-(1→ units with sulfate esters at C-2/C-4 of →6)-β-d-Galp-(1→, C-6 of →3)-β-d-Galp-(1→ and C-3 of →6)-α-d-Glcp-(1→ units. The branches consisting of β-d-Galp-(1→ and →6)-β-d-Galp-(1→ units were located in C-3 of →6)-β-d-Galp-(1→ units. The sulfated polysaccharide exhibited potent anticoagulant activity in vitro and in vivo as evaluated by activated partial thromboplastin time (APTT), thrombin time, and the fibrinogen level. For the APTT, the signal for clotting time was more than 200 s at 100 μg/mL in vitro and at 15 mg/kg in vivo. The obvious thrombolytic activity of the sulfated polysaccharide in vitro was also found. The mechanism analysis of anticoagulant action demonstrated that the sulfated polysaccharide significantly inhibited the activities of all intrinsic coagulation factors, which were less than 1.0% at 50 μg/mL, but selectively inhibited common coagulation factors. Furthermore, the sulfated polysaccharide strongly stimulated the inhibition of thrombin by potentiating antithrombin-III (AT-III) or heparin cofactor-II, and it also largely promoted the inhibition of factor Xa mediated by AT-III. These results revealed that the sulfated polysaccharide from C. oligoclada had potential to become an anticoagulant agent for prevention and therapy of thrombotic diseases.

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Algae accumulate large amounts of polysaccharides in their cell walls or intercellular regions. Polysaccharides from algae possess high potential as promising candidates for marine drug development. In this study, a sulfated polysaccharide, UCP, from the green alga Ulva conglobata Kjellman was obtained by water extraction, anion-exchange, and size-exclusion chromatography purification, and its structure was characterized by a combination of chemical and spectroscopic methods. UCP mainly consisted of →4)-α/β-l-Rhap-(1→, →4)-β-d-Xylp-(1→ and →4)-β-d-GlcAp-(1→ residues. Sulfate ester groups were substituted mainly at C-3 of →4)-l-Rhap-(1→ and C-2 of →4)-β-d-Xylp-(1→. Partial glycosylation was at C-2 of →4)-α-l-Rhap-(1→ residues. UCP possessed a potent immunomodulatory effect in vitro, evaluated by the assays of lymphocyte proliferation and macrophage phagocytosis. The immunomodulatory activity of UCP in vivo was further investigated using immunosuppressive mice induced by cyclophosphamide. The results showed that UCP markedly increased the spleen and thymus indexes and ameliorated the cyclophosphamide-induced damage to the spleen and thymus. UCP could increase the levels of white blood cells, lymphocytes, and platelets, and improve the hematopoietic inhibition caused by cyclophosphamide. Moreover, UCP significantly promoted the secretions of the immunoglobulin (Ig)G, IgE, and IgM. The data demonstrated that UCP is a novel sulfated polysaccharide and may be a promising immunomodulatory agent.

Purpose: To investigate the antitumor effects of ambrosin sesquiterpene lactone on drug-resistant MDA-MB-231 breast cancer cells. Methods: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used for cell viability studies. Apoptotic effects were determined using 4′,6-diamidino2-phenylindole (DAPI) staining assay, while Annexin V/PI was used for the quantification of apoptosis. Levels of reactive oxygen species (ROS) were determined by flow cytometry using DCFH-DA fluorescence staining while the effects of ambrosin on apoptosis and Wnt/beta-catenin signaling pathway-allied proteins were evaluated by Western blotting assay. Results: Ambrosin significantly suppressed the viability of MDA-MB-231 cells in a dose- and time-dependent manner (p < 0.05). Results from Annexin V/PI staining revealed that ambrosin induced production of apoptotic crops and blebbing of plasma membrane in MDA-MB-231 cells. Furthermore, annexin V/PI assay results showed increases in percentage of cells in different stages of apoptosis. Thus, ambrosin promoted caspase-dependent-apoptosis in MDA-MB-231 cells. Moreover, ambrosin enhanced the formation of ROS in MDA-MB-231 cells, as was evident from increased DCF- fluorescence (p < 0.05). The results also showed dose-dependent inhibition of Wnt/beta-Catenin signaling pathway by ambrosin. Conclusion: Ambrosin exerts a chemo-preventive effect on breast cancer cells via induction of programmed cell death, enhanced ROS production, caspase activation and suppression of Wnt/beta- catenin signaling. These findings have potential benefits for breast cancer research and drug discovery.