Fucoidans have shown potential inflammatory modulating activity, particularly as selectin blockers. Fucoidans have also been studied for their potential in addressing systemic and local inflammation in the digestive tract when orally ingested, and on the skin when applied topically. The reported mechanisms of action are suggestive of the inhibition of inflammatory enzymes and increased integrity of cellular junctions.
Fucoidan extracts have been shown to be successful inhibitors in models of inflammatory disease. Research using dietary fucoidan from Undaria pinnatifida has shown a decrease in inflammation in diverse settings, including a UV irradiated mouse model (Maruyama, 2015). Dietary fucoidan from Fucus vesiculous, produced by Marinova, was also shown to decrease inflammation in a colitis model (Lean, 2015). Fucoidan extracts have been shown to lessen liver damage caused by inflammation in an animal model (Lim, 2015). In another animal model, fucoidan extracts were shown to inhibit the development of osteoarthritis (Lee, 2015), a disease that involves the painful degradation of joint function. Rheumatoid arthritis is an inflammatory disease and osteoarthritis also has an inflammatory component. Human clinical studies utilising fucoidans produced by Marinova have also explored a potential future role for these extracts in alleviating symptoms (Myers, 2010; Myers, 2011) and in reducing in the chronic inflammation marker, IL6 (Myers, 2011).
The selectin blockade activity of fucoidan extracts has been widely reported and reviewed (Fitton, 2011). L-Selectins are cell surface receptors on white blood cells, which perform a braking function for the cells. This braking function allows the receptors to roll on endothelial surfaces and ultimately enter tissue spaces, reducing inflammation. In a range of models, fucoidans have been shown to inhibit selectins and thus leukocyte adhesion, thereby increasing the potential to reduce systemic inflammation (Fitton, 2011). P-selectins are expressed on platelets, which are essential for the process of clotting. Cancer cells use both L-selectins and P-selectins as a way to metastasize to other tissue sites, sticking to the endothelial lining of blood vessels. In an animal model, a fucoidan extract was shown to inhibit this process (Gassman, 2010). Fucoidan extracts have also been developed as a radiolabeled P-selectin marker for the imaging of platelet-rich thrombi (Rouzet, 2011).
Some fucoidans have been shown to inhibit the cyclooxygenase (COX) and lipoxygenase (LOX) enzymes, which are key targets for anti-inflammatory drug development (Dewi, 2016). COX has two well-known isoforms: COX-1 and COX-2. COX-2 predominates at sites of inflammation, while COX-1 is expressed primarily in the gastrointestinal tract, where at normal levels, it is essential for normal gut function. LOX inhibition is desirable, as it is associated with the progression of cancer, psoriasis and atherosclerosis. Research conducted by Marinova indicated that high purity fucoidan extracts were able to inhibit LOX-15, COX-1 and COX-2 enzymes very effectively at low concentrations (IC50 <100 mcg/ml) in an in vitro model.
Inflammation of the gut
The potential inhibition of gut inflammation by fucoidan extracts has also been extensively studied. In a colitis model, using dietary fucoidan extracts produced by Marinova, clinical signs of inflammation, bowel histology and cytokine analysis were suggestive of a strong inhibitory effect of oral fucoidan towards colitis (Lean, 2015). In animal models, fucoidans have also been shown to inhibit aspirin-induced inflammation of the stomach (Choi, 2010), and increase the integrity of tight junctions (Shang, 2016). Increasing the integrity of tight junctions within the gastrointestinal tract may elicit favourable changes in bowel microbiome, which, in turn, has been associated with decreased inflammation.
In topical formulations, high purity fucoidan produced by Marinova has been shown to impart a range of inflammatory modulating properties. In a clinical setting, it has been shown to significantly inhibit erythema and water loss from skin when applied before or after exposure to UVA and UVB. Using in vitro skin models, Marinova's high purity fucoidan extracts have also been shown to induce immune response genes. In other in vitro models, they have been shown to inhibit the activity of matrix degrading enzymes such as elastase, collagenase and hyaluronidase, and induce the expression of the ‘anti-ageing’ protein sirtuin (SIRT1) (Fitton, 2015).
It has also been demonstrated that fucoidans may limit the inflammation caused by allergy. Importantly, topically applied fucoidan extracts have been shown to be as effective as cortisone in combatting allergic dermatitis (AD), the most common form of eczema (Yang, 2012). An in vitro study demonstrated that high purity fucoidan extracts produced by Marinova significantly inhibited the adhesion of Staphylococcus aureus – a bacterium typically abundant on the skin of AD patients and known to aggravate this common inflammatory skin condition (Park, 2021). Importantly, the fucoidan did not affect the adhesion of Staphylococcus epidermidis – a common bacterium found on healthy skin.