Marine Algal Fucoidans As Potential Mmpis

Marine algae are reported to produce different polysaccharides including alginates, laminarans, and fucoidans. They usually contain large proportions of l-fucose and sulfate, together with minor amounts of other sugars such as xylose, galactose, mannose, and glucuronic acid. These algal polysaccharides have been attributed with many biological activities such as anticoagulant, antithrombotic, antitumoral, and antiviral activities. Especially fucoidans from marine algae have been reported to exhibit outstanding biological activities that aid for human health. Fucoidans (Fig. 10.2) are sulfated polysaccharides that are exclusively found in seaweeds in their cell wall. This polysaccharide ingredient is composed of polymer of a1 ! 3-linked 1-fucose with sulfate groups on some of the fucose residues at the four positions (Patankar et al., 1993). Recently, fucoidan is being studied extensively due to potential antitumor, antiviral, anticomplement, and anti-inflammatory activities (Chizhov et al., 1999). Brown algae-derived fucoidan has been reported to show strong inhibition ability on UVB-induced MMP-1 expression in vitro. In an investigation by Moon et al., human skin fibroblast (HS68) cells were pretreated by various concentrations of fucoidan and then subjected to UVB irradiation (100 mJ/cm2). As it is known that UVB irradiation induces the production of MMPs by activating cellular signaling transduction pathways, which are responsible for the degradation or synthesis inhibition of collagenous extracellular matrix in connective tissues, causing skin pho-toaging. Their results have suggested that fucoidan from algae has successfully inhibited the expression of MMP-1 by the suppression of extracellular signal-regulated kinase (ERK). Moreover, in fucoidan-trea-ted cells, the expression of MMP-1 mRNA has been significantly reduced (Moon et al., 2008). As brown edible algae are considered as dietary food stuff, the consumption of brown algae that are rich in fucoidan could be beneficial in reducing the risk of MMP-related diseases.

Similarly, another research group reported the MMP inhibitory effect of a 16-kDa fucoidan fraction from seaweeds on the parameters involved

FIGURE 10.2 Chemical structure of fucoidan unit.

in connective tissue breakdown. It was observed that this 16 kDa fucoidan was able to successfully inhibit the gelatinase A secretion and stromelysin 1 induction by interleukin-1 p on dermal fibroblasts in vitro. In addition, ex vivo studies using the tissue sections of human skin have revealed that this polysaccharide was able to minimize human leukocyte elastase activity resulting in the protection of human skin elastic fiber network against the enzymatic proteolysis due to this serine proteinase (Senni et al., 2006). These findings clearly suggest the potential role of seaweed fucoidans in reducing the risk of some inflammatory pathologies that involve extracellular matrix degradation by MMPs. Usually, high molecular weight (HMW) fucoidans are known to bind to the growth factors, such as fibroblast growth factor (FGFs), and protect them from proteolysis (Belford et al., 1993). The therapeutic ability of fucoidans thought to be associated with the fact that they can release the glycosaminoglycan-bound stromal-derived factor-1 (SDF-1) from its tissue storage sites. SDF-1 mobilizes medullary progenitors which could participate in angio-genesis with vascular endothelial growth factor (VEGF) and FGF (Salvucci et al., 2002; Sellke et al., 1996). A fraction of low molecular weight (LMW) fucoidan (7 ± 2 kDa) obtained by radical depolymerization of HMW extracts from brown seaweed have been reported to promote therapeutic revascularization in a rat model of critical hindlimb ischemia (Luyt et al., 2003). Normally, MMP-9 plays an important role in both animal models of cerebral ischemia and human stroke. The expression of MMP-9 is elevated after cerebral ischemia which is involved in accelerating matrix degradation, disrupting the blood-brain barrier, increasing the infarct size, and relating to hemorrhagic transformation (Dong et al., 2009). The therapeutic ability of seaweed fucoidans would be a best option in managing the MMP-associated cerebral ischemia.

Fucoidans isolated from Costaria costata have been reported to possess the MMP inhibition activities. In vitro study using the immortalized human keratinocyte (HaCaT) cell line pretreated with C. costata-derived fucoidans has shown a significant decrease in the UVB-induced MMP-1 expression. Moreover, fucoidan has significantly reduced the expression MMP-1 mRNA and inhibited UVB-induced MMP-1 promoter activity by 37.3%, 53.3%, and 58.5% at 0.01,0.1, and 1 mg/mL, respectively, compared to UVB irradiation alone (Moon et al., 2009). Fucoidan extracts from seaweed Cladosiphon novae-caledoniae Kylin (Mozuku) have reduced the cellular invasiveness in human fibrosarcoma HT1080 cells by suppressing the activity of MMP-2 and MMP-9. Further, it has been reported that these fucoidan extracts suppressed the expression and secretion of an angio-genesis factor, VEGF, thereby reporting the inhibitory effects on invasion and angiogenesis of tumor cells (Ye et al., 2005). Another research group has reported that fucoidan exerts its antiproliferative action. In vitro studies on the cultured AGS human gastric adenocarcinoma cells treated

FIGURE 10.3 Generalized representation of the inhibitory effects of seaweed phlor-otannins and fucoidans on MMP activity.

with fucoidans suggest that fucoidan effectively inhibits the growth of AGS cells by inducing autophagy, as well as apoptosis. They have also reported that the downregulation of antiapoptotic Bcl-2 and Bcl-xL expression, loss of mitochondrial membrane potential, activation of cas-pases, and concomitant degradation of poly-(ADP-ribose) polymerase protein are involved in the fucoidan-induced apoptosis (Park et al., 2011). Thus, fucoidans can be of great potential in controlling the expressions of MMPs that regulate the cell proliferation and metastasis and hence can be better dietary supplements in managing cancers (Fig. 10.3).

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