Extract from “Plastids of Marine Phytoplankton Produce Bioactive Pigments and Lipids”
22.214.171.124. Anti-Oxidant, Anti-Inflammatory and Anti-Mutagenic Activities
Number of works report anti-oxidant properties of microalgae and cyanobacteria [107,110,143]. Most microalgal and cyanobacterial pigments exert strong anti-oxidant activities in vitro and in vivo in animal models (Table 2). It was postulated that circulating anti-oxidants also have a role in the prevention of cardiovascular disease: C-reactive protein and oxidized low-density lipoprotein-cholesterol concentrations, are inversely related to plasmatic concentrations of vitamin C, carotenoids and phenols [144,145,146].
Therefore, dietary anti-oxidants may be protective against the development of inflammatory disease. However, additional intervention trials are required with carotenoids to precise their absorption, metabolism and potential as natural anti-oxidant, anti-inflammatory and anti-mutagenic compounds in vivo. Carotenoids have also a role in regulating gene expression and in inducing cell-to-cell communications .
Astaxanthin (Asta) is a nonprovitamin A found in Haematococcus pluvialis, up to 2–20 g kg−1 on a dry weight basis . It is a powerful anti-oxidant, more effective than vitamins C and E or other carotenoids [149,150]. In particular, it has been reported that the anti-oxidant properties of Asta are about 10 times greater than those of β-carotene, lutein, zeaxanthin, canthaxanthin and over 500 greater than that of α-tocopherol. Thus the term “super vitamin E” has been proposed for Asta [100,103]. Asta has also a great potential to prevent cancer, diabetes and cardiovascular diseases [100,101]. The presence of the hydroxyl and keto endings on each ionone ring explains Asta unique features, such as the ability to be esterified , a higher anti-oxidant activity and a more polar configuration than other carotenoids [38,102,128]. Because of its anti-oxidant and membrane preservation properties, Asta has a considerable potential in the prevention and treatment of various chronic inflammatory disorders, such as cancers, rheumatoid arthritis, metabolic syndrome, diabetes, diabetic nephropathy, and gastrointestinal liver and neurodegenerative diseases, and could provide benefits not only for the cardiovascular system, but also in other inflammatory diseases. Therefore, its daily consumption is a practical and beneficial strategy in human health management . Despite of these studies the molecular mechanism related to the biological activities of Asta is not yet fully understood. In a recent study, Sayo et al.  investigated whether the actions of nonprovitamin A carotenoids including Asta are mediated via retinoid signaling in cultured human keratinocytes. They found that β-carotene, β-cryptoxanthin, lutein, zeaxanthin, and Asta, upregulated HAS3 gene expression and stimulated hyaluronan synthesis. The results suggest that nonprovitamin A can be substituted for retinoids and should be considered as a potential means of improving skin health. The several examples of benefits brought by Asta on health have however to be verified using human trials. To our knowledge, such trials have been started. For instance, Djordjevic et al.  tested the effect of Asta supplementation on muscle enzymes, oxidative stress markers and antioxidant response in elite young soccer players in Serbia. The results suggest that soccer is associated with excessive production of ROS and oxidative stress, which are prevented in Asta-supplemented in young soccer players.
Fucoxanthin (Fuco) is a brown pigment belonging to the class of xanthophylls, with anti-oxidant properties  under anoxic conditions, whereas other carotenoids have practically no quenching abilities, donating electrons as a part of its free-radical quenching function . Fuco protects cells and provides other health benefits : it improves cardiovascular health, blood pressure, and liver functions; it reduces inflammation, cholesterol and triglyceride levels [119,121,124]. Moreover, Fuco has anti-inflammatory effects via inhibitory effects of nitric oxide production [122,123].
Future clinical studies should determine the effectiveness of Asta and Fuco, not only on the vascular structure, but also on cartilage and joint health in at-risk patients or in those with established osteoarthritis .
β-Carotene isan important carotenoid because it displays a pro-vitamin A activity. Because animal cells cannot synthesize this molecule, it is considered as an essential compound in the human body .
Lutein and β-cryptoxanthin may down-regulate factors involved in inflammation associated with osteoarthritis and rheumatoid arthritis . Lutein is currently considered as effective agent for the prevention of a variety of human diseases. Synechoxanthin, isolated in 2008 from the cyanobacteriumSynechococcus sp. strain PCC 7002, has exceptional strong antioxidant properties .
Epidemiologic studies demonstrate an inverse relationship between cancer incidence and dietary carotene intake or blood carotenoid levels, provided the carotene intake is not too high [140,152]. For instance, Moreau et al.  works focalized to carotenoids extracts of the marine diatom Odontella aurita that showed an anti-proliferative effect on cultures of bronchopulmonary and epithelial cells when extracts were added to cell medium. Carotenoids such as astaxanthin or lycopene are active inducers of communication between cells at the cell-gap junctions [100,102,153]. DNA has receptors for specific carotenoids in controlling connexin gene transcription (connexin being a protein that mediates inter-cellular permeability and communication). The immune system cells need intercellular communication to function effectively, so they can be affected by the DNA regulating mechanism of carotenoids. For example, high doses of β-carotene increase the CD4 to CD8 lymphocyte ratio . MDR reversion is often observed. Microalgae pigments may have interest to restore drug sensitivity or reverse MDR in cancer cells, as some of them inhibit or down-regulate drug efflux pumps. As examples, neoxanthin increases rhodamine accumulation in MDR colon cancer cells , inhibits the P346 glycoprotein efflux pump and reverses MDR in doxorubicin-resistant MCF-7 cells and hmdr1-transfected L1210, at 4 and 40 μg mL−1, respectively . Violaxanthin and violeoxanthin are effective MDR modulators in colon, at 4 and 40 μg mL−1, respectively [111,112,134].
Some experiments performed on mices demonstrated that carotenoids (α- and β-carotene) can reduce sharply the immunoglobulin E production. For instance, the reduction of food allergy was observed on animals sensitized to ovalbumine . Another work reported a similar effect of β-carotene combined with vitamin E on splenocytes . Fuco, especially, but also Asta, zeaxanthin and β-carotene have anti-allergic propreties; they can block the aggregation of high affinity receptor for immunoglobin E via inhibiting their translocation to lipid rafts . Fuco anti-allergic activity was recently evidenced using a rodent mast cells model [117,118].
Fuco and its metabolite fucoxanthinol  limit the risk of obesity [124,125]. Actually, these two marine carotenoids inhibit lipase activity in the gastrointestinal lumen and suppress triglyceride absorption . During normal metabolism, the body produces heat : fuco affects many enzymes involved in fat metabolism determining an increase in the release of energy from fat , thus an increase of thermogenesis.
Treatment with neoxanthin significantly reduces lipid accumulation. Examination of structures and functions suggests that carotenoids containing an allene bond and an additional hydroxyl sustituent on the side group may show suppressive effects on adipocyte differentiation .
126.96.36.199. Protection against Light
To cope with the deleterious effects of excess illumination, photosynthetic organisms have developed photoprotective mechanisms that dissipate the absorbed excess energy as heat from the antenna system. Certain bloom-forming microalgae are “sun-adapted” and have the capacity to synthesize sunscreen pigments . In many microalgae, the cell is made more resistant to UV light by the accumulation in the cell wall of sporopollenin , a carotene-polymer absorbing UV light. Lutein is one of the major xanthophylls found in green microalgae. It selectively accumulates in the macula of the human retina, protects the eyes from oxidative stress, and acts as a filter of the blue light involved in macular degeneration and age-related cataract [131,132,133]. Asta protects against UV light; it is true for microalgae, animals and human beings [38,105]. Fuco inhibits tyrosinase activity, melanogenesis in melanoma and UVB-induced skin pigmentation by topical or oral application .
In cyanobacteria, strong blue-green (or white) light activates a soluble carotenoid protein, the OCP which, by interacting with the phycobilisome, increases energy dissipation in the form of heat, thereby decreasing the amount of energy arriving at the RCs. Consequently, OCP plays a key role in the photoprotective mechanism in cyanobacteria [136,137,138,139] and it is the first photoactive protein identified containing a carotenoid as the photoresponsive chromophore . The fluorescence decrease associated with this energy dissipation in the antenna was called qEcya to differentiate this mechanism from that existing in plants. The qEcya mechanism is not the only one that protects cyanobacteria cells from high irradiance. Mutants lacking zeaxanthin are very sensitive to strong light, even more than mutants lacking the qEcya mechanism, indicating an important role of this carotenoid in photoprotection .
Another protein, called the Fluorescence Recovery Protein (FRP) encoded by the slr1964 gene inSynechocystis PCC 6803, plays a key role in dislodging the red OCP from the phycobilisome and in the conversion of the free red OCP to the orange, inactive, form. As a result, under low light conditions, the FRP mediates the recovery of the full antenna capacity by accelerating the deactivation of the OCP . The amplitude of photoprotection depends on both OCP concentration and FRP concentration but also on the OCP/FRP ratio. Therefore, the synthesis of FRP and OCP is probably strictly regulated to accomodate both concentration and OCP/FRP ratio to the right level of photoprotection.