Potential antiallergic compounds derived from marine macroalgae

1. Phlorotannins

Brown algae have been recognized as a rich source of phlorotannins, which are formed by the polymerization of phloroglucinol (1,3,5-trihy-droxybenzene) monomer units and biosynthesized through the acetate-malonate pathway. Notably, phlorotannins exhibited versatile beneficial bioactivities such as antioxidant, anticancer, antidiabetic, antihuman immunodeficiency virus, matrix metalloproteinase enzyme inhibition, and antihypertensive (Vo and Kim, 2010). In relation to antiallergic properties, many phlorotannins from brown algae were considered as potential natural inhibitors of allergic reactions. Phlorotannins of fucodiphloroethol G, eckol, dieckol, 6,6'-bieckol, and phlorofucofuroeckol A (PFF-A) purified from E. cava were evidenced to be efficient against A23187- or FceRI-mediated histamine release from KU812 and RBL-2H3 cells. The inhibitory mechanism was known due to the blockade of these compounds on binding activity between IgE and FceRI (Le et al., 2009; Li et al., 2008). Similarly, phlorotannins of dioxinodehydroeckol (DHE) and PFF-A obtained from Ecklonia stolonifera showed a suppressive effect on cell surface expression of FceRI, and total cellular protein and mRNA levels of the FceRI a chain in KU812 cells (Shim et al., 2009a). Further, both of these compounds exerted inhibitory effects against the elevation of intracellular calcium level and histamine release from anti-FceRI a chain antibody (CRA-1)-stimulated cells. On the other hand, several phlorotannins of eckol, dieckol, 6,6'-bieckol, 6,8'-bieckol, 8,8'-bieckol, PFF-A, and PFF-B from Eisenia bicyclis and E. arborea have been recognized as strong inhibitors of hyaluronidase, phospholipase A2, cyclooxygenase, and lipoxygenases (Shibata et al., 2002, 2003; Sugiura et al., 2008b, 2009), which correlated to suppression of eicosanoid synthesis and release (leu-kotriene and prostaglandin) from RBL cells (Sugiura et al., 2009). Among these phlorotannins, PFF-B exposed the strongest activity against hista-mine and p-hexosaminidase release from RBL cells with IC50 value of 7.8 mM (Sugiura et al., 2006a, 2007). Accordingly, these bioactive phlor-oglucinol derivatives may be promising candidates for the design of novel inhibitors of FceRI-mediated allergic reaction and enzymes in allergic inflammation.

2. Polysaccharides

Marine algae are the most important source of polysaccharides and the chemical structure of the polymers varies according to the alga species. In recent years, various polysaccharides isolated from marine algae have been used in the fields of food, cosmetic, and pharmacology due to their beneficial biological activities, such as antivirus, anticoagulant, anticancer, and anti-inflammation (Vo and Kim, 2010). A role of polysaccharides from marine macroalgae as antiallergic agents has been suggested. Alginic acid, a naturally occurring hydrophilic colloidal polysaccharide obtained from the several species of brown seaweeds, exhibited inhibitory effects on hyaluronidase activity and histamine release from mast cells (Asada et al., 1997). Further, the antiallergic activities of alginic acid have also been found due to its suppressive effects on the activity and expression of histidine decarboxylase, the production of IL-1 p and TNF-a, protein level of nuclear factor (NF)-kB/Rel A in the nucleus, luciferase activity, and DNA-binding activity in PMA plus A23187-stimulated HMC-1 cells (Jeong et al., 2006). Noticeably, alginic acid oligosaccharide (ALGO), a lyase lysate of alginic acid, was able to reduce IgE production in the serum of mice immunized with beta-lactoglobulin (Uno et al., 2006; Yoshida et al., 2004). Moreover, antigen-induced Th2 development was blocked by ALGO treatment via enhancing the production of IFN-g and IL-12 and downregulating IL-4 production in splenocytes of mice (Yoshida et al, 2004).

In addition, porphyran, a sulphated polysaccharide isolated from red seaweeds, has been recognized to be effective against different allergic responses. According to Ishihara et al. (2005), porphyran of red algae Porphyra tenera and Porphyra yezoensis were capable to inhibit the contact hypersensitivity reaction induced by 2,4,6-trinitrochlorobenzene through decreasing the serum levels of IgE and IFN-g in Balb/c mice. Meanwhile, fucoidan from Undaria pinnatifida reduced the concentrations of both IL-4 and IL-13 in bronchoalveolar lavage fluid and inhibited the increase of antigen-specific IgE in OVA-induced mouse airway hypersensitivity (Maruyama et al., 2005). In the recent study, Yanase et al. (2009) have reported that the peritoneal injection of fucoidan inhibited the increase of plasma IgE via suppressing a number of IgE-expressing and IgE-secreting B cells from OVA-sensitized mice (Yanase et al., 2009). On the other hand, the inhibitory effect of fucoidan on IgE production was proved due to preventing Ce germline transcription and NF-kB p52 translocation in B cells (Oomizu et al., 2006). However, the effect of fucoidan was not observed if B cells were prestimulated with IL-4 and anti-CD40 antibody before the administration of fucoidan. These observations suggested that fucoidan may not prevent a further increase of IgE in patients who have already developed allergic diseases and high levels of serum IgE. Conversely, Iwamoto et al. (2010) have determined that fucoi-dan effectively reduced IgE production in both peripheral blood mono-nuclear cells from atopic dermatitis patients and healthy donors (Iwamoto et al., 2010). These findings indicated that fucoidan suppresses IgE induction by inhibiting immunoglobulin class switching to IgE in human B cells, even after the onset of atopic dermatitis.

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