H&PC Today - Household and Personal Care Today, vol. 11(3) May/June 2016

combination of fucose mono-, di- and trimers. The second interest of this technology is to saturate the fucose molecules in sulfated groups. The fi gure below shows the lowest possible molecular weight and the highest degree of sulfation.

Consequences on biological activityThe biological activity of fucoidan derivatives is in inverse proportion to the molecular weight of these molecules. The shorter the saccharide chain, the greater the biological activity of the fucoidan derivative. The biological activity is also in direct correlation to the fucoidan derivative’s degree of sulfation. In effect it is these sulfated derivatives which, by attaching themselves to biological receptors, lead

to cosmetic activity (5).

Skin absorption: By using hydrolysis technology it is possible to obtain highly ionised water-soluble oligofucoidans with an extremely low molecular weight. These 3 criteria define the skin absorption capacity of a cosmetic agent. This is why Fucoreversetm is so easily and so rapidly absorbed across the skin’s barrier (5).

FUCOREVERSETM – PROTECT AND REPAIR THE EXTRACELLULAR MATRIX (ECM)

The passing of the years has negative effects on the skin and its properties, worsening them. There are biochemical, histological and physiological alterations that include ECM functional impairment, collagen and elastin degradation, and slower metabolism rate. The degenerative changes that come with age can cause facial skin to lose its vibrancy. A major factor in this process is the degradation of the extracellular matrix of the dermal connective tissue.

The extracellular matrix in the dermis is composed of a molecular network (collagen, elastin and glycosaminoglycans) between the fi broblasts which ensures the skin’s structure and tone. When the deterioration and the repair of this network are imbalanced, wrinkles appear and the skin loses its fi rmness. Fucoidans protect this network by blocking the enzymes responsible for the deterioration of the extracellular matrix as well as the pro-infl ammatory cytokines which damage the collagen (6, 7). Fucoreversetm also acts as a repairing agent by stimulating the metabolism of the fi broblasts and collagen synthesis. With these 2 synergistic actions, Fucoreversetm helps to reverse the signs of ageing by bringing back the skin’s structure and fi rmness.

This kelp has developed a defense system enabling it to resist the extreme conditions of the Iroise Sea (storms, ocean currents and very high tides). The fucoidan structure in the cell walls of these algae plays a protective and restorative role in rebuilding the tissues after a storm. (2).

Marine glycotechnology involves hydrolysing these fucoid ans polymers to obtain precise fractions of biologically active oligosaccharides.

THE UNIQUE COMPOSITION OF FUCOREVERSETM

What are Fucoidans?Fucoidans are polymers composed of sulfated fucose. They are insoluble high molecular weight molecules: 50 to 1000 kDalton. They are known to demonstrate a wide range of biological activities including stimulation of the cellular metabolism and immunomodulation.

Fucoidans are a class of non-gelling, sulphated polysaccharides found only in brown macro algae. Their sugar backbone composition, structure and sulphation patterns differ according to their origin and the extraction techniques used. The common feature is a high content of the backbone sugar « fucose ». Fucoidans have diverse bioactivity including heparin-like anticoagulant activity, inhibition of selectins and scavenger receptors, inhibition of viral entry to cells and immunomodulation. Fucoidans also inhibit UVB-induced MMP expression in vitro, and are a good inhibitors of the dermal remodelling enzymes called matrix metalloproteinases (3). Interestingly, topical fucoidan was as effective as the gold standard topical steroid cream when applied to anatopic dermatitis model in mice (4).

Fucoreversetm glycotechnology:The fucoidans can be hydrolysed until an extremely low molecular weight is obtained. Fucoreversetm is a

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KEYWORDS: Keywords....

Abstract A macroalgae-derived extract has been developed for use in cosmetic formulations. Wild-grown luminaria from Iroise sea were sourced to extract and hydrolyse fucoidan compounds. These oligo-

fucoidans are then purified in order to keep only the very low molecular weight fractions saturated in sulphur which are the most biologically active. The oligo-fucoidans are known for their potential to regulate inflammation as well as their capacity to stimulate cell metabolism and collagen synthesis, act as biological messengers. Its invivo efficacy on wrinkles reduction and on skin roughness was evaluated on a panel of 42 female volunteers that applied a cream containing 1,5% of Fucoreversetm on the face, twice a day for 30 days. The reduction of wrinkles depth was measure at the beginning and after 30 days of treatment. The skin presented an average wrinkles reduction of 9,1% after 30 days compared with placebo, so the ant wrinkle efficacy of the marine ingredient was proved.

Marine glycobiology to reverse the signs of ageing

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INTRODUCTION

The marine environment is a rich source of biological and chemical diversity. Interestingly, algae developed adaptive responses to environmental stress (UV, temperature, bacteria, pressure, turbulence…) and thus they are able to produce saccharides or other active molecules. Laminaria seaweeds are one of the most frequent seaweed surviving in the extreme conditions of the Iroise sea, mainly due to their ability to produce and secrete some fucoidans compounds in their cellular walls. Fucoreversetm is a hydrolysed fucoidan extracted from these luminaria. In vitro and in vivo tests show anti-ageing properties.

FROM THE IROISE SEA (BRITTANY COAST, FRANCE) TO THE MARINE GLYCOBIOLOGY

Cellular communication: the role of glycobiologyFor many years the cosmetic industry has focused its attention on peptides and their capacity to attach themselves to cellular receptors, thereby propagating biological messages. Peptides, however, are not the only molecules to have these properties. Certain specifi c oligosaccharides such as fucose also play a similar role, thus demonstrating alternative biological modes of action which we call “glycobiology”. One of the major promises made by glycosciences is the

identifi cation of communication phenomena via the specifi c sugars of the cellular membranes and via the sugars of the extracellular matrix, to adapt the specifi c action of the active ingredients to certain applications. The potential cosmetic applications which could result are attracting an increasing number of researchers who see in the “biological intelligence” of these oligosaccharides a revolution in our knowledge about the skin’s metabolism. All these sugar chemical messengers are naturally present in the body and are manufactured using 8 essential sugars of which fucose is an important one.

Oligosaccharides chains are essential compounds for human skin as they have a key role in processes like cellular protein maintenance, stress recovery and cell to cell communication, and as constituents of cell walls and signifi cant integral membrane proteins, where they infl uence cellular interaction. Such molecules mediate the vital adhesion between cells that allows functional tissues as well as cell-substrate unions serving as receptors for adhesion ligands, as it occurs with fi broblasts and fi bronectin (1).

Algae from the Iroise Sea (Brittany coast): an unrivalled source of essential sugarsFucose is the major constituent of a high molecular weight polymer called fucoidan. The specifi city of the fucoidans present in the cellular membranes of Laminaria from the Iroise Sea is their high sulfated fucose content.

CHARLES-HENRI MORICELESSONIA, Croas Ar Neizic, 29800 Saint-Thonan, France

Industry perspective

H&PC Today - Household and Personal Care Today, vol. 11(3) May/June 2016

Charles-Henri Morice

Figure 2. Iroise Sea.Figure1. Laminaria seaweeds.

Figure 3. Chemical structure: Polymer of Fucoidan. Figure 4. Chemical structure: Fucoreversetm

FOCUS ON ANTIAGEING: actives, formulation delivery, testing

H&PC Today - Household and Personal Care Today, vol. 11(3) May/June 2016

CONCLUSION

Thanks to its unique composition, Fucoreversetm acts by protecting and repairing the ECM, thereby reversing the signs of ageing. Wrinkle depth is significantly reduced in comparison to a placebo group.

REFERENCES

1. A Varki. Biological roles of oligosaccharides: all of the theories are correct. Glycobiology, 3, 97-130. 1993.

2. Robuchon M, Le Gall L, Mauger S, Valero M. Contrasting genetic diversity patterns in two sister kelp species co-distributed along the coast of Brittany, France. Mol Ecol 2014 Jun; 23(11): 2669-85.

3. Moon HJ, Lee SH, Ku MJ et al. Fucoidan inhibits UVB-induced MMP-1 promoter expression and down regulation of type 1 procollagen synthesis in human skin fibroblasts. Eur J Dermatol 2009; 19 (2): 129-34.

4. Yang JH. Topical application of fucoidan improves atopic dermatitis symptoms in NC/Nga mice. Phytother Res 2012; 26 (12):1898:903.

5. Robert, C., Robert, A.M. Effect of L-fucose and fucose-rich oligo-and polysaccharides (FROP-s) on skin aging: penetration, skin tissue production and fibrillogenesis. Skin Res Technol. 2005 Feb; 11 (1):47-52.

6. Senni K, Gueniche F, Foucault-Bertaud et al. Fucoidan a sulfated polysaccharide from brown algae is a potent modulator of connective tissue proteolysis. Arch Biochem Biophys 2006; 445 (1): 56-64.

7. N. Isnard, I.Fodil-Bourahla, A.m. Robert, L. Robert. Pharmacology of skin aging. Stimulation of glycosaminoglycan biosynthesis by L-fucose and fucose-rich polysaccharides, effect of in vitro aging of fibroblasts. Biomedicine & Pharmacotherapy 58 (2004) 202-204.

It is considered whether the product works on the wrinkles depth. In order to reach this goal, a clinical-intrumental study is carried out on 42 volunteers showing wrinkles on the crow’s foot area, divided in two groups according the randomization lists: the groupA reveived the active product whereas the group B received placebo. Product efficacy is evaluated after 28 days of product use by means of non-invasive skin bioengineering technique to evaluate skin profilometry. The active product used contain 1.5% of fucoreversetm.

Skin surface is quantitatively assessed by LIFEVIZ Micro. It is a non-contact in vivo skin measurement device based on structured light projection. In conjunction with a comprehensive 3-D measurement and evaluation software, the sensor allows to evaluate the wrinkle depth.

Results: Efficacy of Fucoreversetm on the crow’s foot area after 28 days.After using 1.5% Fucoreversetm twice daily for 28 days, statistics show that Fucoreversetm significantly decreases the depth of crow’s foot wrinkles by 9.1 % on average, versus placebo P<0.05 Student test.

Efficacy of Fucoreversetm on anti-irritant properties The study showed a significant decrease in irritations and redness as shown in the above photo. The subjects who used the product containing Fucoreversetm had good skin tolerance whereas those who used the placebo cosmetic base had moderate tolerance with a few cases of skin irritation. These results show the use of Fucoreversetm to calm sensitive skin.

11H&PC Today - Household and Personal Care Today, vol. 11(3) May/June 2016

Fucoreversetm stimulates type 1 collagen synthesis compared with the negative controlProtocol: The determination of collagen synthesis is carried out by quantitative dye-binding method. The chromogen agent used in the assay is Sirius Red. The collagen concentration is calculated by means of date interpolation on a standard curve obtained with know and increasing collagen concentrations.

Results: The data are reported as the percentage increase of collagen synthesis after cells exposure to the test item respect untreated cells. The treatment with fucoreversetm has positively modulated collagen synthesis in the considered experimental system. All recorded variations are significant vs negative control (CTR-). Fucoreversetm has a significant stimulatory effect on collagen synthesis compared to the non-treated control group: + 23.7 % in the 0.15% dose; + 31.1 % in the 1.5% dose.

CLINICAL STUDY

Protocol: The aim of the study is to evaluate the safety of use, the cosmetic acceptability and the efficacy of fucoreversetm.

IN VITRO TESTS

The effect of Fucoreversetm on the fibroblasts proliferation and synthesis of collagen has been evaluated on human dermal fibroblasts. Fucoreversetm was tested at 2 concentrations: 0.15% and 1.5%. Untreated cells were used as negative control (CTR-).

Fucoreversetm stimulates fibroblast proliferation Protocol: Culture medium containing tested product was added to the wells containing cells in the G0 phase of cell cycle. At the end of incubation period, the cell viability was evaluated and the increasing proliferating rate compared to untreated control cell culture.

Results: The data are reported as the percentage increase of cell proliferation after cells exposure to the test item respect untreated cells. The treatment with fucoreversetm has positively modulated cell proliferation in the considered experimental system. All recorded variations are significant vs negative control (CTR-). A significant increase in the proliferation of fibroblasts compared to the non-treated group of: +35.5% in the 0.15% dose; 51.1% in the 1.5% dose.

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Figure 5. Fibroblast proliferation relative to untreated cells.

Figure 6. Collagen synthesis relative to untreated cells.

Figure 7. Crow’s feet wrinkles depth after treatment with Fucoreversetm at 1.5%, versus placebo.

Figure 8. Macrophotography effect of 1.5% Fucoreversetm on crow’s feet wrinkles.