The effect of a fraction of phlorethol (CcPh), one of the polyphenolic compounds isolated from the brown alga Costaria costata (Turn.) Saund (Laminariales), on gametes and embryogenesis of the sea urchin Strongylocentrotus intermedius (A. Agassiz, 1864) was studied. Using a model of developing sea urchin embryos, it was shown that phlorethol at concentrations of ≤700 μg/mL did not exert a cytotoxic effect on early developmental stages (from the zygote to the 16-celled stage blastomere). The embryotoxic effect of phlorethol that caused the death of 50

The inhibitor of human α-N-acetylgalactosaminidase (α-NaGalase) was isolated from a water–ethanol extract of the brown algae Costaria costata. Currently, tumor α-NaGalase is considered to be a therapeutic target in the treatment of cancer. According to NMR spectroscopy and mass spectrometric analysis, it is a high-molecular-weight fraction of phlorethols with a degree of polymerization (DP) equaling 11–23 phloroglucinols (CcPh). It was shown that CcPh is a direct inhibitor of α-NaGalases isolated from HuTu 80 and SK-MEL-28 cells (IC50 0.14 ± 0.008 and 0.12 ± 0.004 mg/mL, respectively) and reduces the activity of this enzyme in HuTu 80 and SK-MEL-28 cells up to 50% at concentrations of 15.2 ± 9.5 and 5.7 ± 1.6 μg/mL, respectively. Molecular docking of the putative DP-15 oligophlorethol (P15OPh) and heptaphlorethol (PHPh) with human α-NaGalase (PDB ID 4DO4) showed that this compound forms a complex and interacts directly with the Asp 156 and Asp 217 catalytic residues of the enzyme in question. Thus, brown algae phlorethol CcPh is an effective marine-based natural inhibitor of the α-NaGalase of cancer cells and, therefore, has high therapeutic potential.

The ability of fucoidans to scavenge reactive oxygen species still remains a subject of debate in scientific literature, as shown by an analysis of the results of recent studies on the antioxidant activity (AOA) of fucoidans. On the one hand, in vitro and in vivo experiments provide evidence that fucoidans of brown algae can modulate diseases associated with oxidative stress by regulating the antioxidant defense systems and signaling pathways. On the other hand, the use of cell-free assay systems has revealed a relationship between the antioxidant activity attributed to fucoidans and the polyphenolic compounds extracted along with them. The polyphenolic compounds of brown algae referred to as phlorotannins are also known as potent antioxidants. Since the vast majority of studies use various commercial preparations or extracts containing fucoidan and polyphenolic compounds without measuring the level of the latter in polysaccharide samples, there is still no clear understanding of whether fucoidans or co-extracted polyphenolic compounds are a priority component providing AOA.

Fucoidans are biologically active sulfated polysaccharides of brown algae. They have a great structural diversity and a wide spectrum of biological activity. This review is intended to outline what is currently known about the structures of fucoidans and their radioprotective effect. We classified fucoidans according to their composition and structure, examined the structure of fucoidans of individual representatives of algae, summarized the available data on changes in the yields and compositions of fucoidans during algae development, and focused on information about underexplored radioprotective effect of these polysaccharides. Based on the presented in the review data, it is possible to select algae, which are the sources of fucoidans of desired structures and to determine the best time to harvest them. The use of high purified polysaccharides with established structures increase the value of studies of their biological effects and the determination of the dependence "structure biological effect".

The effects of polyphenolic impurities on the biological activity of fucoidan samples from the brown alga Fucus distichus subsp. evanescens were studied using the model of developing embryos of the sea urchin Strongylocentrotus intermedius. The embryotoxic action of fucophloretol from F. evanescens (IC50 = 96.90 ± 12.20 μmol/L) and cucumarioside A7 (a triterpene glycoside) from Cucumaria frondosa subsp. japonica (IC50 = 0.39 ± 0.01 μmol/L) was assessed. The ability of fucoidans with different levels of polyphenolic impurities to partially or completely reduce the embryotoxic action of cucumarioside A7 from C. japonica has been shown.

The anticancer and radiosensitizing effects of high-molecular-weight phlorethols CcPh (Mw = 2520 Da) isolated from the brown algae of Costaria costata on human colorectal carcinoma HCT 116 and HT-29 cells were investigated. Phlorethols CcPh possessed cytotoxic activity against HT-29 (IC50 = 92 μg/mL) and HCT 116 (IC50 = 94 μg/mL) cells. CcPh at non-toxic concentrations inhibited the colony formation in colon cancer cells and significantly enhanced their sensitivity to low non-toxic X-ray irradiation. The combinatory effect of radiation and CcPh was synergistic (Combination index < 0.7). Algal phlorethols might be prospective candidates as radiosensitizers to improve the scheme of radiotherapy.

Fucoidans are a group of homo-and hetero-polysaccharides, which necessarily contains residues of sulfated α-L-fucose. Fucoidans are found only in brown algae. These polysaccharides exhibit a wide spectrum of biological activity and have a great therapeutic potential. Enzymes capable of catalyzing the degradation of fucoidans are absent in the mammalian enzyme system. The question arises: is the transformation of fucoidan in mammals, particularly in human possible? Studies in vivo (in situ) and in vitro have demonstrated that high molecular weight fucoidans are absorbed across rat intestinal epithelial cells, accumulated by liver macrophages, and characterized by low levels in blood and urine. Using the example of the Okinawa Prefecture (Japan) residents, it was shown that Cladosiphon okamuranus alga is digested and the fucoidan contained in this alga is absorbed in the human body.

The inhibitors of recombinant fucoidanase FFA2 from the marine bacterium Formosa algae KMM 3553(T) were found among the metabolites of brown algae Fucus evanescens and Costaria costata. NMR spectroscopy and mass spectrometry analysis showed that high molecular weight phlorethols (degree of polymerization (DP) of 12-25 monomers) from C. costata (ICc) and fucophloretol (DP = 3) from F. evanescens (IFe) were inhibitors of fucoidanase. To inhibit one mole of FFA2 fucoidanase about two molecules of the ICc inhibitor or 7 molecules of the IFe inhibitor are needed. It has been suggested that the effectiveness of inhibition increases with the increasing molecular weight of phlorotannins. An irreversible type of inhibition was established.

This review is devoted to the analysis of publications on studies of phlorotannins, which are polyphenolic metabolites of brown algae. Their properties, the pathway of biosynthesis, and the structural diversity and classification of phlorotannins, as well as the methods for their isolation and determination of their metabolic profiles, are examined. The antioxidant, antitumor, and antimicrobial activities of phlorotannins and their role in the regulation of enzyme activity are discussed. These properties of phlorotannins determine the prospects of using phlorotannins in pharmacology.

Fucoidan hydrolase inhibitors were discovered for the first time. Metabolites in the aqueous EtOH extract of Fucus evanescens inhibited specifically the activity of enzymes involved in catabolism of brown-alga polysaccharides, i.e., fucoidanases (recombinant FFA from the marine bacterium Formosa algae KMM 3553T and PPF from the marine mollusk Patinopecten yessoensis) and glycosidases (recombinant α-L-fucosidase FucFa from F. algae and β-D-glucosidase G-II from the marine mollusk Littorina sitkana). The purified fucophlorethol fraction isolated from this extract inhibited recombinant fucoidanase FFA in the concentration range 10–50 μg/mL.

The review summarizes results of studies of effects of sulfated polysaccharides from seaweed on herpesviruses and the course of herpesvirus infections. Importance of this problem is determined by the prevalence of herpesviruses that can persist in the human body and demonstrate a high degree of immune mimicry and resistance to antiviral drugs. A wide range of physiological action of sulfated polysaccharides, receptor agonists of innate and adaptive immune cells, which possess potent antiviral, antioxidant and anti-inflammatory activities, open the possibility of their use for creation of new generation pharmacological substances and drugs with associated activity for the treatment of herpesvirus infections.

Laminaran, fucoidan, and alginate were isolated from the brown alga Coccophora langsdorfii collected in the Japan Sea. The structural characteristics of polysaccharides were investigated by NMR spectroscopy. The laminaran was determined as β-d-glucan, which consisted of 80% of 1,3- and 20% of 1,6-linked residues and was terminated with mannitol. The alginate was a guluronic acid-rich polysaccharide (M/G=0.85). Fucoidan, sulfated α-l-fucan, contained a linear backbone of alternating (1→3)- and (1→4)- linked α-l-fucopyranose residues with sulfate at C2 and C4 of (1→3)-α-l-fucopyranose residues. Anticancer activity of this fucoidan was investigated in comparison with activity of fucoidan having similar linear backbone from the brown alga Fucus evanescens. The fucoidan from C. langsdorfii significantly inhibited colony formation of SK-MEL-5 and SK-MEL-28 melanoma cells (the percentage of inhibition was 28 and 76, respectively) and weakly inhibited colony formation of breast adenocarcinoma cells MDA-MB-231 (the percentage of inhibition was about 5). Similar results were obtained for fucoidan from F. evanescens; the percentage of inhibition of colony formation of SK-MEL-5 and SK-MEL-28 melanoma cells was 54 and 56, respectively. The inhibition of colony formation of breast adenocarcinoma cells MDA-MB-231 was weak. We suppose that other sulfated and partially acetylated fucoidans consisting of (1→3)- and (1→4)-linked α-l-fucopyranose residues may suppress progression of melanoma cell colony formation similar to fucoidans of C. langsdorfii and F. evanescens.

Brown alga Fucus evanescens, widespread in the Far Eastern seas of Russia, is valuable source of sulfated polysaccharides – fucoidans with beneficial biological activities. The most homogenous fraction of fucoidan from F. evanescens was shown to be molecule containing linear main chain of alternating 2-sulfated 1,3- and 1,4-linked α-L-fucose residues. Few sulfate groups were found in position 4 of some 1,3-linked fucose residues. Acetyl groups occupied free C-3 of 1,4-linked residues and/or the C-4 of 1,3-linked fucose residues. Enzymatic hydrolysis, mild acid hydrolysis and autohydrolysis of native fucoidan were used for elucidation of the fine structural characteristics of fucoidan from F. evanescens. The aim of this review to summarize published data on biological activities of fucoidan from F. evanescens: antiviral, anticoagulant, thrombolytic, hepatoprotective, immunomodulatory, anticancer, and their practical application.