Many studies have already highlighted that the polysaccharides released to the culture medium by some marine microalgae present antiviral bioactivity against different kinds of viruses, either mammalian or otherwise (Table 3). Radonic et al. [36] and Chen et al. [56] have reviewed the antiviral effects of several sPS on different host cell-lines. Calcium-Spirulan, an intracellular polysaccharide produced by A. platensis, inhibited the replication of several viruses in vitro by inhibiting the penetration of the virus into the different host cells used [40,43]. Radonic and co-workers [36] also showed that the polysaccharide released into medium by A. platensis and P. purpureum exhibited antiviral activity in vitro and in vivo against two strains of Vaccinia virus and an Ectromelia virus.

The antiviral activity is probably the most studied quality exhibited by sulphated polysaccharides of marine microalgae, especially that produced by Porphyridium. The mechanisms for this activity are not yet completely understood. As happens with heparin, the anionic nature of the sPS makes it a good candidate to protect against viruses. Several mechanisms have been proposed. Hayashi and colleagues [40] noted that sPS inhibited infection by different viruses by inhibiting the penetration of viral particles into host cells, but other mechanisms can also be the involved, such as the inhibition of attachment/adsorption, or even replication during the early phases of the virus cycle [41,87], without any toxicity to the host cells [37].

While photoautotrophs, microalgae/cyanobacteria are highly exposed to oxidative and radical stresses, therefore accumulating effective anti-oxidative scavenger complexes to protect their own cells from free radicals [7]. Oxidation of lipids by reactive oxygen species (ROS), like hydroxyl radicals, hydrogen peroxide, and superoxide anion, can affect the safety of pharmaceuticals and also decrease the nutritional quality of foods.

Sulphate polysaccharides released by marine microalgae may not only function as dietary fibre [54], but have also demonstrated the ability to prevent the accumulation and the activity of free radicals and reactive chemical species, therefore, acting as protecting systems against these oxidative and radical stress agents (Table 4). According to Tannin-Spitz et al. [57], the sPS from Porphyridium exhibited antioxidant activity against the autooxidation of linoleic acid, and inhibited oxidative damage to 3T3 cells that might be caused by FeSO₄. They demonstrated that bioactivity was dose-dependent, correlating positively with sulphate content of the sPS, and referred to the possibility of the glycoprotein to contribute to the antioxidant properties. It was even suggested that the antioxidant activity of this polymer relied on its ability to act as a free radical scavenger [57]. Sun et al. [58] prepared different molecular-weight polysaccharide-derived products of P. cruentum, using a hermetical microwave technique, and found that the lower molecular-weight fragments (6.55–256 kDa) showed higher antioxidant activity, better protecting mouse cells and tissues from oxidative damage by inhibiting lipid peroxidation induced by FeSO₄ and ascorbic acid. Free radical scavenging of some of the EPS fragments was significantly higher at the same, or even lower, concentration than that reported previously for vitamin C [88]. But strangely, they found no scavenging activity and no inhibition of oxidative damage in cells and tissues for the crude high molecular sPS from Porphyridium cruentum [58].

Sulphated exopolysaccharide from Rhodella reticulata also showed to have antioxidant activity, the effects being dose-dependent [56]. Unlike what happens with the sPS from Porphyridium [58], crude sPS from Rhodella exhibited higher antioxidant properties than the polysaccharide-modified samples, these demonstrating lower radicals scavenging activity [56]. These researchers found that all the different samples of sPS from R. reticulata had a stronger ability against superoxide anion radical scavenging than α-tocopherol, the crude polysaccharide being twice as strong as α-tocopherol.

Polysaccharides from marine microalgae, like Porphyridium, Phaeodactylum, and Chlorella stigmatophora, were found to show pharmacological activities, such as anti-inflammatory activity and as immunomodulatory agents (Table 4). Direct stimulatory effect of Phaeodactylum tricornutum on the immune cells was evidenced by the positive phagocytic activity assayed either in vitro or in vivo, and the activity of the extract of sPS from C. stigmatophora showed immunosuppressant effects [28]. As reported for the polysaccharide from Ulva rigida, a green seaweed [89], the sPS p-KG03 from the marine dinoflagellate G. impudicum also activates the production of nitric oxide and immunostimulates the production of cytokines in macrophages [90]. However, on the other hand, inhibition of leukocyte migration seems to be related to the anti-inflammatory activity of the polysaccharides [62]. As leukocyte movement to the site of injury contributes to additional cytokine release and production of nitric oxide, therapeutics has to be effective against this over-inflammation. Matsui and co-workers [62] found that sPS from Porphyridium is a good candidate for this role as it inhibited the movement and adhesion of polymorphonuclear leukocytes in vitro, and inhibited the development of erythema in vivo as well.

When studying the effects of EPS-derived products, Sun [55] showed that EPS presented immunostimulating activity in mice with S180 tumours, by increasing both spleen and thymus index, and also spleen lymphocyte index. Smaller fragments of sPS have also demonstrated the capacity to improve the production of NO in mouse macrophages. In his Ph.D. Thesis, Sun [55] referred to the fact that sulphate content has a positive correlation with the immunomodulatory system. Further, Namikoshi [91] noted that sPS can stimulate the immune system by triggering cells and humour stimulation. This shows the capacity of marine unicellular algae sPS to directly stimulate the immune system.

One potentially promising activity of polysaccharides is the ability to prevent tumour cell growth. The homopolysaccharide of G. impudicum, that has immunomodulatory properties, suppressed tumour cell growth, both in vitro and in vivo [91,92], by stimulating the innate immune system (Table 4). Calcium-Spirulan of Arhrospira (Spirulina) was reported to prevent pulmonary metastasis, also preventing the adhesion and proliferation of tumour cells. It is also promising in treating spinal cord injuries and as matrices for stem cell cultures [93].

Geresh et al. [64] demonstrated that the high molecular weight oversulphated EPS from Porphyridium inhibited neoplastic mammalian cell growth, and Shopen-Katz et al. [66] had previously reported that biomass of this microalga could prevent the proliferation of colon cancer in rats. On the other hand, Sun [55] noted that non-modified or high molecular-weight fragments of sPS from P. cruentum showed no inhibition of tumour cell growth. Some smaller EPS-derivatives showed significant activity on Sarcoma 180 tumour cell proliferation in rats though. However, Geresh and co-workers [64] also found that the non-modified sPS had no significant inhibition at the same concentration as EPS-derivatives. Furthermore, in a recent study, Gardeva et al. [65] reported the strong anti-tumour activity exhibited by the polysaccharide of P. cruentum. They found that this sulphated polymer strongly inhibited Graffi myeloid tumour proliferation in vitro and in vivo, that the activity was dose-dependent, and that survival time of hamsters was enhanced in 10–16 days. Gardeva and co-workers [65] suggested that the anti-tumour activity could be related to its immunostimulating properties, and observed that EPS from Porphyridium could be a good candidate as an anticancer agent.

Recently, Jiao et al. [94] reported in their review what was being done with sulphated polysaccharides produced by macroalgae, including the capacity of sPS to reduce total cholesterol and serum triglycerides (in rats). This is an area that has not been sufficiently explored in regards to microalgae (Table 4). However, when Ginzberg and co-workers fed chickens with biomass of Porphyridium with EPS, they found that cholesterol was reduced either in serum or egg yolk of chickens, modifying fatty acid profile, and improving carotenoid content in egg yolk as well [60]. In addition, rats fed with Porphyridium and R. reticulata biomass, the polysaccharides of which contain dietary fibres, showed a decrease in the serum cholesterol and triglycerides; hepatic cholesterol levels were also improved, the levels of VLDL had also considerably lowered, and no toxic effects were noticed in the animals [53,54,95]. Furthermore, Dvir and co-workers [95] also reported that rodents fed with Rhodella biomass presented lower levels of insulin and glucose. An experiment conducted by Huang and co-workers [61] also showed the capacity of sPS from Porphyridium to significantly lower glucose levels in the blood of diabetic mice, causing no modifications in the pancreatic island cells and no fibrosis, or haemorrhagic necrosis in cells, either.

These experiments suggest the strong potential of sulphated polysaccharides to be used as hypolipidaemic and hypoglycaemic agents. They could also be used as sources of nutraceuticals due to their content in fibres, the ability of bile acid binding and cation exchange, and the properties of faecal bulking as well [53,54]. Sulphated polysaccharides from unicellular algae are also promising substances in reducing coronary heart disease, due to their hypocholesterolaemic effects [53,54].

Mechanisms involved in the role of dietary fibres, in lowering cholesterol, are not yet completely understood, but Oakenful [96] proposed that it could be related to the increase of the viscosity of the intestinal contents, which influences nutrient absorption, micelle formation, and decreasing lipid absorption. In addition, the decrease in serum cholesterol levels and the increase in bile excretion, caused by disruption of enterophatic circulation of bile acids, was suggested as another possible explanation [97,98].

Sulphated polysaccharides from unicellular marine algae revealed the ability to block the adhesion of pathogenic microorganisms, which suggests the hypothesis to be used in anti-adhesive therapeutics. As a matter of fact, several sPS presented greater inhibition of the adherence of both Helicobacter pylori to HeLa S3 cell line and three fish pathogens to spotted sand bass gills, gut, and skin cultured cells [30] (Table 4).

The major role of carbohydrates as recognition sites on the cell surfaces to which microorganisms can attach to, allowing infection, has already been evidenced [99]. Heparan sulphate glycosaminoglycan was identified as one of those receptors in host cells [100]. These researchers suggested that this interaction could be associated to the net charge and molecular stereochemistry of the polymer.

Nevertheless, a therapy based on sulphated polysaccharides may have some risks; therefore, further studies are needed in order to know their cytotoxic and anticoagulant properties.

There are several studies on the anticoagulants isolated from seaweeds (marine macroalgae), which are presented in a recent review by Wijesekara et al. [101], but only a few references on microalgae. On the one hand, it was stated that the anticoagulant activity is associated to the high sulphate content of the polysaccharides. However, this characteristic can be a problem when considering their use for the treatment of virus-induced diseases. On the other hand, Hasui et al. [37] found no anticoagulant activity in the sPS of Cochlodinium polykrikoides, in spite of the 7%–8% sulphate of the polysaccharide. This suggests that the anticoagulant properties of the polysaccharides do not depend only on the percentage of sulphate residues, but rather, mostly on the distribution/position of sulphate groups and probably on the configuration of the polymer chains, as it was stated by Ginzberg et al. [85] and Pereira et al. [102].

This is one of the lesser known applications for the sPS and very little has been published on this issue (Table 4). Nevertheless, Arad et al. [68] have proved the superior biolubricant power of sPS from Porphyridium. Exocellular sulphated polysaccharide of Porphyridium has already shown good lubrication ability due to its rheological characteristics [103]. Arad and co-workers [68] prepared an experiment where the lubricating properties of sPS were compared to the most used hydrogel lubricant, hyaluronic acid. They simulated efforts of joints, both when walking and running, and found a better quality from the EPS from Porphyridium as its rheological characteristics showed to be stable at higher temperatures than most lubricants used, whose viscosity decreases along with a decrease of lubricity. These researchers also found that a 1% solution of polysaccharide presented the best friction properties under high loads, and its viscosity did not suffer any significant change when incubated with hyaluronidase, with standing degradation by this enzyme. This experiment shows the potential of sPS from Porphyridium to be an excellent candidate to substitute hyaluronic acid as a biolubricant. It may also be a promising substance to be part of joint-lubricating solutions, as was stated in the patent proposed by Arad and Atar [63], to mitigate degenerative joint disorders caused by arthritis. The effects of the solutions containing EPS from Porphyridium were tested by injecting them into the joints of rabbits’ knees.

Another little known field of application is as drag-reducers. Only a few studies were conducted in order to determine whether polysaccharides had the potential of drag-reducing, to broaden their functionalities for engineering applications (Table 4). The drag-reducing properties of polysaccharides were tested in some EPS from marine microalgae [71], but Gasljevic et al. [70] recently studied the potential of several marine microalgal polysaccharides as drag-reducers. P. cruentum and R. maculata were the ones whose polysaccharides showed the higher drag-reducing power at lower concentrations, followed by Schizochlamydella (former Chlorella) capsulata. These researchers found that to have the same level of drag-reduction effectiveness, 25% more polysaccharide of R. maculata is required than of P. cruentum, and almost three times as much as the polysaccharide of S. capsulata [70].

As happens with polysaccharides from seaweeds [104,105], EPS from unicellular marine algae could also find some application in the health food industry, and in nutraceuticals and functional foods.

Other areas, as diverse as cosmetics or as ion-exchangers, could also be possible due to the chemical composition and rheological characteristics of the marine microalgal sPS.

Prophylactic therapy in microbial infections might also be a promising activity as exopolysaccharides from marine microalgae have already shown the ability to block microbial cytoadhesion to host cells [30] and to inhibit growth of Salmonella enteritidis [50].

Finally, besides all these applications, adhesion properties of the sPS produced by microalgae seem to play an important role in either the locomotion of some algae [106] or in the aggregation of soil and sand particles [107,108], influencing stability and cohesiveness of sediments.