Seaweed is more than the wrap that keeps rice together in sushi. Seaweed biomass is already used for a wide range of other products in food, including stabilising agents. Biorefineries with seaweed as feedstock are attracting worldwide interest and include low-volume, high value-added products and vice versa. Scientific research on bioactive compounds in seaweed usually takes place on just a few species and compounds. This paper reviews worldwide research on bioactive compounds, mainly of nine genera or species of seaweed, which are also available in European temperate Atlantic waters, i.e. Laminaria sp., Fucus sp., Ascophyllum nodosum, Chondrus crispus, Porphyra sp., Ulva sp., Sargassum sp., Gracilaria sp. and Palmaria palmata. In addition, Undaria pinnatifida is included in this review as this is globally one of the most commonly produced, investigated and available species. Fewer examples of other species abundant worldwide have also been included. This review will supply fundamental information for biorefineries in Atlantic Europe using seaweed as feedstock. Preliminary selection of one or several candidate seaweed species will be possible based on the summary tables and previous research described in this review. This applies either to the choice of high value-added bioactive products to be exploited in an available species or to the choice of seaweed species when a bioactive compound is desired. Data are presented in tables with species, effect and test organism (if present) with examples of uses to enhance comparisons. In addition, scientific experiments performed on seaweed used as animal feed are presented, and EU, US and Japanese legislation on functional foods is reviewed.

Bioactive compounds in seaweed: functional food applications and legislation

Fucoidan refers to a type of polysaccharide which contains substantial percentages of L-fucose and sulfate ester groups, mainly derived from brown seaweed. For the past decade fucoidan has been extensively studied due to its numerous interesting biological activities. Recently the search for new drugs has raised interest in fucoidans. In the past few years, several fucoidans' structures have been solved, and many aspects of their biological activity have been elucidated. This review summarizes the research progress on the structure and bioactivity of fucoidan and the relationships between structure and bioactivity.

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Fucoidan: Structure and Bioactivity

Citrus Flavonoids: molecular structure, biological activity and nutritional properties: a review

Sulfated polysaccharides and their lower molecular weight oligosaccharide derivatives from marine macroalgae have been shown to possess a variety of biological activities. The present paper will review the recent progress in research on the structural chemistry and the bioactivities of these marine algal biomaterials. In particular, it will provide an update on the structural chemistry of the major sulfated polysaccharides synthesized by seaweeds including the galactans (e.g., agarans and carrageenans), ulvans, and fucans. It will then review the recent findings on the anticoagulant/antithrombotic, antiviral, immuno-inflammatory, antilipidemic and antioxidant activities of sulfated polysaccharides and their potential for therapeutic application.

Chemical Structures and Bioactivities of Sulfated Polysaccharides from Marine Algae

Biological activities and potential health benefits of sulfated polysaccharides derived from marine algae

Fucoidan from Sargassum sp. and Fucus vesiculosus reduces cell viability of lung carcinoma and melanoma cells in vitro and activates natural killer cells in mice in vivo

Background We showed that fucoidan, extracted from dietary seaweed, could inhibit tumor growth. However, the mechanism of Mekabu (Sporophyll of Undaria pinnatifida) fucoidan antitumor activity and how it enhances the immune response remains unknown. Materials and methods We examined the effect of Mekabu fucoidan in P-388 tumor-bearing mice and in T cell-mediated NK cell activity in normal mice. Results The survival of mice was prolonged when Mekabu fucoidan was administered for 4 days before tumor cell inoculation, compared with non-treated mice. Fucoidan significantly enhanced the cytolytic activity of NK cells and increased the amount of IFN-gamma produced by T cells up to about 2-fold compared with non-treated mice. Conclusion The anti-tumor effect of Mekabu fucoidan appears to be mediated by IFN-gamma-activated NK cells.

Antitumor activity and immune response of Mekabu fucoidan extracted from Sporophyll of Undaria pinnatifida.

Fucoidan from Mekabu (sporophyll of Undaria pinnatifida), a dietary alga, exerts antitumor activity possibly through enhancing the immune response. The present report describes the effects of dietary Mekabu fucoidan on the tumor growth of mouse A20 leukemia cells and on T cell-mediated immune responses in T cell receptor transgenic (DO-11 - 10 - Tg) mice. The animals were fed with a diet containing 1% Mekabu fucoidan (0.034 +/- 0.003 g/mouse/day) for 10 days and subcutaneously (s. c.) inoculated with A20 leukemia cells. Thereafter, the mice were fed with the diet containing fucoidan for 40 days. Mekabu fucoidan inhibited tumors by 65.4 %. We studied how the killer activities of T cell-mediated and natural killer (NK) cells are augmented in DO-11 - 10 mice fed with Mekabu fucoidan. The cytolytic activities of ovalbumin (OVA), which is specific against OVA-transfected A20 (OVA-A20) B lymphoma cells, and NK cells against YAC-1 were significantly enhanced in the mice fed with fucoidan compared with a basic diet. Thus, these findings suggested that Mekabu fucoidan mediates tumor destruction through Th1 cell and NK cell responses.

The role of NK cells in antitumor activity of dietary fucoidan from Undaria pinnatifida sporophylls (Mekabu)

Leucine-rich repeat kinase 2 (LRRK2), a large protein kinase containing multi-functional domains, has been identified as the causal molecule for autosomal-dominant Parkinson's disease (PD). In the present study, we demonstrated for the first time that (i) LRRK2 interacts with tau in a tubulin-dependent manner; (ii) LRRK2 directly phosphorylates tubulin-associated tau, but not free tau; (iii) LRRK2 phosphorylates tau at Thr181 as one of the target sites; and (iv) The PD-associated LRRK2 mutations, G2019S and I2020T, elevated the degree of tau-phosphorylation. These results provide direct proof that tau is a physiological substrate for LRRK2. Furthermore, we revealed that LRRK2-mediated phosphorylation of tau reduces its tubulin-binding ability. Our results suggest that LRRK2 plays an important role as a physiological regulator for phosphorylation-mediated dissociation of tau from microtubules, which is an integral aspect of microtubule dynamics essential for neurite outgrowth and axonal transport.

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LRRK2 phosphorylates tubulin-associated tau but not the free molecule: LRRK2-mediated regulation of the tau-tubulin association and neurite outgrowth.

Fucose-containing sulfated polysaccharides (FCSPs) extracted from seaweeds, especially brown macro-algae, are known to possess essential bioactive properties, notably growth inhibitory effects on tumor cells. In this work, we conducted a series of in vitro studies to examine the influence of FCSPs products from Sargassum henslowianum C. Agardh (FSAR) and Fucus vesiculosus (FVES), respectively, on proliferation of melanoma B16 cells and to investigate the underlying apoptosis promoting mechanisms. Cell viability analysis showed that both FCSPs products, i.e., FSAR and FVES, decreased the proliferation of the melanoma cells in a dose-response fashion, with FSAR being more potent at lower dosages, and FVES being relatively more anti-proliferative than FSAR at higher dosages. Flow cytometric analysis by Annexin V staining of the melanoma cells exposed to the FCSPs products confirmed that both FSAR and FVES induced apoptosis. The FCSPs-induced apoptosis was evidenced by loss of plasma membrane asymmetry and translocation of the cell membrane phospholipids and was accompanied by the activation of caspase-3. The FCSPs bioactivity is proposed to be attributable to distinct structural features of the FCSPs, particularly the presence of sulfated galactofucans (notably in S. henslowianum) and sulfated fucans (notably in F. vesiculosus). This study thus indicates that unfractionated FCSPs may exert bioactive effects on skin cancer cells via induction of apoptosis through cascades of reactions that involve activation of caspase-3.

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Fucose-Containing Sulfated Polysaccharides from Brown Seaweeds Inhibit Proliferation of Melanoma Cells and Induce Apoptosis by Activation of Caspase-3 in Vitro

Hiroko Maruyama

Papers

Fucoidan from Sargassum sp. and Fucus vesiculosus reduces cell viability of lung carcinoma and melanoma cells in vitro and activates natural killer cells in mice in vivo

Antitumor activity and immune response of Mekabu fucoidan extracted from Sporophyll of Undaria pinnatifida.

The role of NK cells in antitumor activity of dietary fucoidan from Undaria pinnatifida sporophylls (Mekabu)

LRRK2 phosphorylates tubulin-associated tau but not the free molecule: LRRK2-mediated regulation of the tau-tubulin association and neurite outgrowth.

Fucose-Containing Sulfated Polysaccharides from Brown Seaweeds Inhibit Proliferation of Melanoma Cells and Induce Apoptosis by Activation of Caspase-3 in Vitro