Carotenoids from microalgae to block oxidative stress

Reactive oxygen species (ROS) are normal products of aerobic metabolism involved in cellular biochemical processes, including: signal transduction, gene expression and transcription and the activation of cell signaling cascades.¹ ROS are reactive chemical species having a single unpaired electron in an outer orbit. The increase of external ROS exposure, the decrease of antioxidant levels and the high ROS endogenous production induce excess levels of ROS, a disruption of redox signaling and control - known as oxidative stress.² This state leads to lipid peroxidation, protein oxidation and nitration, and DNA fragmentation that ultimately affect cell membrane structures, enzyme functions and gene expression.

Oxidative stress have widely been implicated in the pathogenesis of many chronic diseases such as cardiovascular pathologies, neurodegenerative pathologies,³ cancer and age related diseases.^4,5 New therapeutic molecules capable of blocking the oxidative stress are of crucial importance. Because of their anti-inflammatory and antioxidant properties carotenoids have been proposed for the prevention of chronic diseases.^6,7 Epidemiological studies suggest that carotenoids prevent the oxidation of free radical-dependent of LDL, cholesterol, proteins or DNA, by capturing free radicals and by reducing stress induced by ROS.⁸

Carotenoids are fat-soluble pigments. Over 750 structurally defined compounds are present in nature, plants and microorganisms. They are directly accumulated from food or partially modified by metabolic reactions in animals. Carotenoids are divided into two major classes based on their structural elements; carotenes, constituted by carbon and hydrogen (e.g. β-carotene, α-carotene and lycopene), and xanthophylls, constituted by carbon, hydrogen, and additionally oxygen (e.g. lutein, b-cryptoxanthin, zeaxanthin, astaxanthin and fucoxanthin).⁹ The presence of conjugated double bonds allows carotenoids to accept electrons from reactive species, and then neutralize free radicals.¹⁰ Besides, some carotenoids have been shown not only to have a direct action but also the ability to modulate gene expression of endogenous antioxidant pathways.

Some of strains of microalgae have extensively been studied for their carotenoid production, including: astaxanthin from Haematococcus pluvialis, β-carotene from Dunaliella salina and Spirulina, zeaxanthin from Synechocystis sp., lutein from Chlorella protothecoides, etc. Specific advantages in the use of microalgae include simple and fast cultivation, processing and harvesting cycle. However, the existence of a rigid cell walls in some algal species limits the efficiency in recovery of bioactive compounds. This is, therefore, a significant bottleneck in the overall bioprocess materials.⁸

One of the well-known carotenoid is astaxanthin, a natural molecule that shows strong antioxidant activity.¹¹ Astaxanthin protective action involves an antioxidant mechanism based on the activation of its hydroxyl groups, which results in the formation of an ortho-dihydroxy-conjugate polyene system acting as a chain-breaking antioxidant. This molecule has shown promising results in animals and also in human experiments by the decrease of blood pressure and the increase of HDL rate. A number of studies show that natural astaxanthin extracted from H. pluvialis is more active than synthetic one and could present therapeutic properties for the treatment of atherosclerosis and cardiovascular disease.^11,12 Moreover, growing evidences suggest that astaxanthin has potential health-promoting effect in the prevention and treatment of other diseases such metabolic syndrome,¹³ skin disease,¹⁴ neurodegenerative pathologies.¹⁵

Lutein is another prominent carotenoid found in several algae species, i.e. in Scenedesmus almeriensis, Chlorella, Chlorella vulgaris, Scenedesmus obliquus, Dunaliella salina and Mougeotia sp.¹⁶ Lutein has similar physicochemical properties to astaxanthin, and it has been used for applications related to human health such as age-related macular degeneration and cardiovascular diseases. It has been stated that in a typical diet the lutein intake is lower than the daily need, and it is recommended to use a supplement containing lutein.^17-19

A combination of two or more lipophilic antioxidants could also allow synergistic effects, like the elimination of reactive nitrogen species and inhibition of lipid peroxidation.⁶ Natural extracts of carotenoids are a mixture of molecules with higher activities when compared to synthetics ones. Combination of phycocyanin and β-carotene contributed to antioxidant, immunomodulatory, and anti-inflammatory properties of Spirulina,²⁰ while, the ERK1/2, JNK, p38, and IκB signaling pathways are mediators in its beneficial properties.²¹

Several studies have confirmed the antioxidant and anti-inflammatory properties might attribute to carotenoids. In addition, treatment with carotenoids showed a reduction in markers of oxidative stress and inflammation without adverse effects.¹² Nevertheless, the optimal administration and delivery systems needed to improve carotenoid bioavailability are still under investigation. Since most of the researches carried out have been based on animals and in vitro models, the efficiency of microalgae carotenoids in human remains to be established. Future clinical surveys should focus on large patients cohorts. Besides, it is still needed to improve the understanding of their biological mechanisms of action to determine their efficacy in the potential prevention and treatment of chronic diseases.

Ethical approval

There is none to be declared.

Competing interests

The authors declare no competing interests.

References

1. Hancock JT, Desikan R, Neill SJ. Role of reactive oxygen species in cell signalling pathways. Biochem Soc Trans 2001;29:345–50.
2. Jones DP. Redefining Oxidative Stress. Antioxid Redox Signal 2006; 8:1865-79.
3. Lin MT, Beal MF. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 2006;443:787-95. doi: 10.1038/nature05292. [Crossref]
4. Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative stress, inflammation, and cancer: How are they linked? Free Radic Biol Med 2011;49:1603-16. doi: 10.1016/j.freeradbiomed.2010.09.006. [Crossref]
5. Khansari N, Shakiba Y, Mahmoudi M. Chronic inflammation and oxidative stress as a major cause of age-related diseases and cancer. Recent Pat. Inflamm. Allergy Drug Discov 2009;3:73–80.
6. Stahl W, Sies H. Antioxidant activity of carotenoids. Mol Aspects Med 2003;24:345-51.
7. Rao AV, Rao LG. Carotenoids and human health. Pharmacol Res 2007;55:207–16.
8. Gong M, Bassi A. Carotenoids from microalgae: a review of recent developments. Biotechnol Adv 2016;34:1396-412. doi: 10.1016/j.biotechadv.2016.10.005. [Crossref]
9. Delgado-vargas F. Natural pigments: carotenoids, anthocyanins, and betalains--characteristics, biosynthesis, processing, and stability. Crit Rev Food Sci Nutr 2000;40:173-289. doi: 10.1080/10408690091189257. [Crossref]
10. Di Pietro N, Di Tomo P, Pandolfi A. Carotenoids in Cardiovascular disease prevention. JSM Atheroscler 2016;1:1–13.
11. Régnier P, Bastias J, Rodriguez-Ruiz V, Caballero-Casero N, Caballo C, Sicilia D, et al. Astaxanthin from Haematococcus pluvialis prevents oxidative stress on human endothelial cells without toxicity. Mar Drugs 2015;13:2857-74. doi:10.3390/md13052857. [Crossref]
12. Fassett RG, Coombes JS. Astaxanthin: a potential therapeutic agent in cardiovascular disease. Mar Drugs 2011;9:447-65.
13. Hussein G, Nakagawa T, Goto H, Shimada Y, Matsumoto K, Sankawa U, et al. Astaxanthin ameliorates features of metabolic syndrome in SHR/NDmcr-cp. Life Sci 2007;80:522-9.
14. Masaki H. Role of antioxidants in the skin: anti-aging effects. J Dermatol Sci 2010;58:85–90.
15. Wolf AM, Asoh S, Hiranuma H, Ohsawa I, Iio K, Satou A, Iet al. Astaxanthin protects mitochondrial redox state and functional integrity against oxidative stress. J Nutr Biochem 2010;21:381-9.
16. Mäki-Arvela P, Hachemi I, Murzin DY. Comparative study of the extraction methods for recovery of carotenoids from algae: Extraction kinetics and effect of different extraction parameters. J Chem Technol Biotechnol 2014;89:1607-26. doi:10.1002/jctb.4461. [Crossref]
17. Naguib YMA. Antioxidant activities of astaxanthin and related carotenoids. J Agric Food Chem 2000;48:1150-4.
18. Santocono M, Zurria M, Berrettini M, Fedeli D, Falcioni G. Lutein, zeaxanthin and astaxanthin protect against DNA damage in SK-N-SH human neuroblastoma cells induced by reactive nitrogen species. J Photochem Photobiol B Biol 2007;88:1-10.
19. McNulty H, Jacob RF, Mason RP. Biologic Activity of carotenoids related to distinct membrane physicochemical interactions. Am J Cardiol 2008;101:20D-29D. doi:10.1016/j.amjcard.2008.02.004. [Crossref]
20. Chen HW, Yang TS, Chen MJ, Chang YC, Wang EIC, Ho CL, et al. Purification and immunomodulating activity of C-phycocyanin from Spirulina platensis cultured using power plant flue gas. Process Biochem 2014;49:1337-44.
21. Wu Q, Liu L, Miron A, Klímová B, Wan D, Kuca K. The antioxidant, immunomodulatory, and anti-inflammatory activities of Spirulina: an overview. Arch Toxicol. 2016;90:1817-40. doi:10.1007/s00204-016-1744-5. [Crossref]