Bioactive compounds from plants, algae, fungi and other microorganisms have gained much attention in cosmetic product development. Active substances can be found in microorganisms that are exposed to extreme outdoor conditions and therefore have developed special adaptation techniques.

One such example is the microalgae Haematococcus pluvialis (H. pluvialis), which is commonly found in small transient freshwater basins and is able to survive under extreme conditions by producing astaxanthin, a reddish pigment that belongs to a family of carotenoids.

Another example of an active ingredient with great appeal to the cosmetic industry is beta-1,3/1,6-glucan from baker’s yeast (Saccharomyces cerevisiae). It is a naturally occurring polysaccharide in the cell wall of yeast and has shown promise in supporting the body’s natural defenses.

Here we will discuss research studies on these two active ingredients in response to oxidative stress followed by sun exposure and immune responses originating in the skin.

Protective Roles of the Skin
Organs in the human body vary according to their structure, size and function. Some of them are vital and others are not. Although skin may not be thought of as a vital organ, it is an indispensable protective cover of the body against mechanical injury and infections from pathogens.¹ In addition, the skin protects internal tissues and organs against ultraviolet (UV) light from the sun.² The skin also contains immune cells that support the renewal of skin tissue and actively fight infection.³

Despite the important protective role of skin, its function will inevitably decrease due to less efficient renewal processes and weaker immunity with age, and because of exposure to environmental factors. This results in a less firm, elastic and dense skin, impairing its ability to protect the body.⁴ There is little to be done to postpone chronological aging and its effect on skin, as skin is subjected to aging processes in the same pattern as all internal organs. However, skin is also heavily influenced by exogenous factors and environmental assaults, such as smog and other pollutants, tobacco smoke, alcohol consumption, stress, sleep deprivation and poor nutrition.

Although small amounts of UV light are beneficial for people and essential for the production of vitamin D in the skin, exposure to high levels of UV light increases pigmentation and reduces skin elasticity, causing premature aging. Excess UV light also misbalances the immune responses within the skin, reducing the body’s ability to protect itself.⁵

Being the outside of the body, the skin is one of the most susceptible organs to damage caused by UV light. Protective skin care is regarded as a major strategy for maintaining skin integrity and its function. In addition to sunscreens, products with active ingredients used either orally or topically, may prevent and/or repair the harmful effects of the sun.

Astaxanthin & Skin Health
Under normal conditions, skin is exposed to low levels of reactive oxygen species (ROS) that are formed as a natural byproduct of normal metabolism. Additionally, ROS can be produced in response to previously mentioned exogenous and environmental factors affecting skin, including UV radiation. Oxidative stress occurs as a result of high metabolic demands and exposure to pro-oxidant agents that increase the total level of cellular ROS, resulting in the damage of proteins, lipids and DNA.

Because of its protective barrier, the load of ROS is higher in the skin compared to other organs. Additionally, normal chronological aging leads to a thinning of skin layers, making the skin more susceptible to UV light and further increasing ROS. For protection against the harmful effects of ROS that are continuously generated, the human body is equipped with enzymatic and non-enzymatic antioxidants.⁶ Diet is a very important source of non-enzymatic antioxidants, such as vitamins A, C and E, beta-carotene, lutein, lycopene and astaxanthin.

Natural astaxanthin is produced by the microalgae H. pluvialis to protect the cells from unfavorable environmental conditions, such as intense UV light. Astaxanthin is a potent antioxidant and has shown diverse health benefits as well as good safety and tolerability.^7-9 Effects of astaxanthin on the skin have been investigated both as dietary supplements and by topical application.

When taken as a dietary supplement, astaxanthin is absorbed along with dietary lipids through passive diffusion into intestinal cells. Through the multiple digestive actions, astaxanthin, as other carotenoids, is incorporated into lipoproteins and secreted back into circulation for delivery to the tissues.¹⁰

There are only a few human studies addressing the dermatological benefit of astaxanthin so far. Nevertheless, pilot studies have demonstrated that astaxanthin can reduce hyperpigmentation, wrinkle formation and improve skin elasticity and moisture content.^11,12 The beneficial effect of astaxanthin on the collagen layer and reduction of visible signs of UV-induced aging was observed already after 4 to 8 weeks. These observations are in accordance with numerous animal studies and studies with cell cultures in vitro.^13-18

When applied topically, astaxanthin has been reported to reduce collagen breakdown, decrease wrinkle formation, prevent UV-induced skin thickening and inhibit melanin production.^19,20 However, topical application of astaxanthin to the skin is challenging because of the poor water solubility of the antioxidant. Topical application of a liposomal formulation containing astaxanthin appears to be a promising solution to this problem.²⁰ There is still little known about how topical application of astaxanthin effects skin immunity. Nevertheless, when applied topically, astaxanthin has been shown to inhibit inflammatory skin conditions in animal models.²¹

Beta-Glucans & Skin Health
Immune cells are particularly sensitive to oxidative changes caused by ROS.²² A star-shaped immune cell in the skin called the Langerhans cell has long cellular extensions, or “arms” called dendrites, stretching to the surface of skin.²³ These cells possess immunomodulatory functions and maintain integrity in normal skin by activating resident skin immune cells.²⁴ Increased exposure to UV light has shown a reduction in the number of the Langerhans cells, decreasing the immune responses and inducing premature skin aging.²⁵

Through evolution, immune cells have developed specialized receptors on their surface that can bind microbe- or pathogen-associated specific molecular structures. Subsequently, this activates immune responses and supports the body’s natural defenses by identifying some conserved non-self-molecules. Naturally occurring cell-wall polysaccharides, beta-glucans, are examples of such conserved non-self-molecules collectively referred to as microbe- or pathogen-associated molecular patterns (MAMPs or PAMPs).^26-28 Beta-glucans, in particular beta-1,3/1,6-glucans from baker’s yeast S. cerevisiae, bind to the specialized receptors of dendrites on Langerhans cells and efficiently activate them.²⁹ The beta-glucans are most likely not absorbed when applied directly on skin. Nevertheless, beta-glucans alert potential immune responses by binding the receptor recognizing MAMPs or PAMPs.³⁰

Topical application of beta-glucan after exposure to UV has been shown to prevent the degradation of Langerhans cells in the skin and to improve the skin’s natural defenses.^31,32 In addition, beta-glucan supports skin repair by increasing the healing rate, stimulating epithelization and increasing the density of immune cells in the damaged area.³³ The effect of beta-glucans on repair processes is likely due to the stimulation of immune cells, such as macrophages, and increasing collagen biosynthesis.^34-38 Topical application of beta-glucans has been shown to reduce wrinkle depth and result in more younger-looking skin.^39,40 Furthermore, topical application of beta-glucans and oral intake of astaxanthin has been shown to work in synergy to increase firmness and elasticity of skin, underlining the strong link between nutrition and skin health.

Conclusions
The awareness of active ingredients from microorganisms and their benefits for human health and wellness have grown tremendously due to expanding knowledge of the mechanisms and effects that such ingredients may represent. Targeting oxidative stress by reducing ROS and improving skin immunity are promising strategies for skin health and offer exciting opportunities for the skin care industry. Astaxanthin is a potent antioxidant that supports healthy skin function by minimizing negative effects of ROS and modulating immune responses. Beta-glucans, on the other hand, contribute to the body’s natural defenses by supporting the physical barrier and cellular immunity. Taken together, these directions are innovative and promising. 

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About the Authors: Lina Cekaite received her PhD in Molecular Medicine from University of Oslo and performed post-doctoral training at University Hospital, Oslo, Norway. She has recently joined NutraQ as a science manager and is working with the astaxanthin product portfolio. Hanne Groegaard holds a Master of Science in Biotechnology from Norwegian University of Science and Technology, Trondheim, Norway. She is currently employed as a science manager at NutraQ and works specifically in the area of new product development of topical beta-glucan. For more information: www.nutraq.com; www.algalif.com

References

1. Kanitakis, J., Eur J Dermatol, 2002.
2. Lucas R, et al., Environmental Burden of Disease Series, No. 13, 2006.
3. Kupper, T.S., et al., Nat Rev Immunol, 2004.
4. Yu, B., et al., Nat Mater, 2016.
5. WHO. 2016 [Available from: http://www.who.int/uv/faq/uvhealtfac/en/.
6. Bhattacharyya, A., et al., Physiol Rev, 2014.
7. Hussein, G., et al., J Nat Prod, 2006.
8. FDA, T.R.A.I., 2000.
9. Guerin, M., et al., Trends Biotechnol, 2003.
10. Bjerkeng, B., et al., Comp Biochem Physiol B Biochem Mol Biol, 2000.
11. Yoon, H.S., et al., J Med Food, 2014.
12. Tominaga, K., et al., Acta Biochim Pol, 2012.
13. Yoshihisa, Y., et al., Exp Dermatol, 2014.
14. O’Connor, I., et al., J Dermatol Sci, 1998.
15. Nakajima, H., et al., Arch Dermatol Res, 2012.
16. Suganuma, K., et al., J Dermatol Sci, 2010.
17. Imokawa, G., et al., Int J Mol Sci, 2014.
18. Camera, E., et al., Exp Dermatol, 2009.
19. Seiki, T., et al., Fragrance Journal, 2001.
20. Hama, S., et al., J Pharm Sci, 2012.
21. Kim, H., et al., Mol Med Rep, 2015.
22. Knight, J.A., Ann Clin Lab Sci, 2000.
23. Silberberg, I., Acta Derm Venereol, 1973.
24. Trautinger, F., Clin Exp Dermatol, 2001.
25. Thiers, B.H., et al., Journal of Investigative Dermatology, 1984.
26. Engstad, R.E., et al., Dev Comp Immunol, 1994.
27. Goodridge, H.S., et al., Nature, 2011.
28. Li, C., et al., Cardiovasc Res, 2004.
29. Adams, E.L., et al., J Pharmacol Exp Ther, 2008.
30. Peiser, M., et al., J Leukoc Biol, 2008.
31. Zulli, F., et al., Euro Cosmetics, 1995.
32. Zulli, F., et al., Int J Cosmet Sci, 1998.
33. Wolk, M., et al., Med Biol, 1985.
34. Browder, W., et al., Surgery, 1988.
35. Portera, C.A., et al., Am Surg, 1997.
36. Medeiros, S.D., et al., Int J Mol Sci, 2012.
37. Zykova, S.N., et al., J Diabetes Investig, 2014.
38. Skjæveland, I., et al., SÅR, 2013.
39. Cognis, Report, 1999.
40. Dermscan, L., Report, 2011.