There is currently much interest in biological active compounds derived from natural resources, especially compounds that can efficiently act on molecular targets, which are involved in various diseases. Astaxanthin (3,3′-dihydroxy-β, β′-carotene-4,4′-dione) is a xanthophyll carotenoid, contained in Haematococcus pluvialis, Chlorella zofingiensis, Chlorococcum, and Phaffia rhodozyma. It accumulates up to 3.8% on the dry weight basis in H. pluvialis. Our recent published data on astaxanthin extraction, analysis, stability studies, and its biological activities results were added to this review paper. Based on our results and current literature, astaxanthin showed potential biological activity in in vitro and in vivo models. These studies emphasize the influence of astaxanthin and its beneficial effects on the metabolism in animals and humans. Bioavailability of astaxanthin in animals was enhanced after feeding Haematococcus biomass as a source of astaxanthin. Astaxanthin, used as a nutritional supplement, antioxidant and anticancer agent, prevents diabetes, cardiovascular diseases, and neurodegenerative disorders, and also stimulates immunization. Astaxanthin products are used for commercial applications in the dosage forms as tablets, capsules, syrups, oils, soft gels, creams, biomass and granulated powders. Astaxanthin patent applications are available in food, feed and nutraceutical applications. The current review provides up-to-date information on astaxanthin sources, extraction, analysis, stability, biological activities, health benefits and special attention paid to its commercial applications.
References
[1]
Higuera-Ciapara, I.; Felix-Valenzuela, L.; Goycoolea, F.M. Astaxanthin: A review of its chemistry and applications. Crit. Rev. Food Sci. Nutr. 2006, 46, 185–196, doi:10.1080/10408690590957188.
[2]
Pashkow, F.J.; Watumull, D.G.; Campbell, C.L. Astaxanthin: A novel potential treatment for oxidative stress and inflammation in cardiovascular disease. Am. J. Cardiol. 2008, 101, 58D–68D.
[3]
Roche, F. Astaxanthin: Human food safety summary. In Astaxanthin As a Pigmenter in Salmon Feed, Color Additive Petition 7C02 1 1, United States Food and Drug Administration; Hoffman-La Roche Ltd.: Basel, Switzerland, 1987; p. 43.
[4]
Sarada, R.; Tripathi, U.; Ravishankar, G.A. Influence of stress on astaxanthin production in Haematococcus pluvialis grown under different culture conditions. Process Biochem. 2002, 37, 623–627, doi:10.1016/S0032-9592(01)00246-1.
[5]
Ranga Rao, A. Production of astaxanthin from cultured green alga Haematococcus pluvialis and its biological activities. Ph.D. Thesis, University of Mysore, Mysore, India, 15 May 2011.
[6]
Sarada, R.; Ranga Rao, A.; Sandesh, B.K.; Dayananda, C.; Anila, N.; Chauhan, V.S.; Ravishankar, G.A. Influence of different culture conditions on yield of biomass and value added products in microalgae. Dyn. Biochem. Proc. Biotechnol. Mol. Biol. 2012, 6, 77–85.
[7]
Kidd, P. Astaxanthin, cell membrane nutrient with diverse clinical benefits and anti-aging potential. Altern. Med. Rev. 2011, 16, 355–364.
[8]
Guerin, M.; Huntley, M.E.; Olaizola, M. Haematococcus astaxanthin: Applications for human health and nutrition. Trends Biotechnol. 2003, 21, 210–216, doi:10.1016/S0167-7799(03)00078-7.
[9]
Yang, Y.; Kim, B.; Lee, J.Y. Astaxanthin structure, metabolism, and health benefits. J. Hum. Nutr. Food Sci. 2013, 1, 1003:1–1003:11.
[10]
Hussein, G.; Sankawa, U.; Goto, H.; Matsumoto, K.; Watanabe, H. Astaxanthin, a carotenoid with potential in human health and nutrition. J. Nat. Prod. 2006, 69, 443–449, doi:10.1021/np050354+.
[11]
Yuan, J.P.; Peng, J.; Yin, K.; Wang, J.H. Potential health promoting effects of astaxanthin: A high-value carotenoid mostly from microalgae. Mol. Nutr. Food Res. 2011, 55, 150–165, doi:10.1002/mnfr.201000414.
[12]
Yamashita, E. Astaxanthin as a medical food. Funct. Foods Health Dis. 2013, 3, 254–258.
[13]
Dhankhar, J.; Kadian, S.S.; Sharma, A. Astaxanthin: A potential carotenoid. Int. J. Pharm. Sci. Res. 2012, 3, 1246–1259.
[14]
Ranga Rao, A.; Sindhuja, H.N.; Dharmesh, S.M.; Sankar, K.U.; Sarada, R.; Ravishankar, G.A. Effective inhibition of skin cancer, tyrosinase, and antioxidative properties by astaxanthin and astaxanthin esters from the green alga Haematococcus pluvialis. J. Agric. Food Chem. 2013, 61, 3842–3851.
[15]
Ranga Rao, A.; Baskaran, V.; Sarada, R.; Ravishankar, G.A. In vivo bioavailability and antioxidant activity of carotenoids from micro algal biomass—A repeated dose study. Food Res. Int. 2013, 54, 711–717, doi:10.1016/j.foodres.2013.07.067.
Ranga Rao, A.; Raghunath Reddy, R.L.; Baskaran, V.; Sarada, R.; Ravishankar, G.A. Characterization of microalgal carotenoids by mass spectrometry and their bioavailability and antioxidant properties elucidated in rat model. J. Agric. Food Chem. 2010, 58, 8553–8559, doi:10.1021/jf101187k.
[18]
Ranga Rao, A.; Sarada, R.; Baskaran, V.; Ravishankar, G.A. Identification of carotenoids from green alga Haematococcus pluvialis by HPLC and LC-MS (APCI) and their antioxidant properties. J. Microbiol. Biotechnol. 2009, 19, 1333–1341.
[19]
Lorenz, R.T. A Technical Review of Haematococcus Algae. NatuRose？ Technical Bulletin #060; Cyanotech Corporation: Kailua-Kona, HI, USA, 1999; pp. 1–12.
[20]
EFSA (European Food Safety Authority). Opinion of the scientific panel on additives and products or substances used in animal feed on the request from the European commission on the safety of use of colouring agents in animal human nutrition. EFSA J. 2005, 291, 1–40.
[21]
Iwamoto, T.; Hosoda, K.; Hirano, R.; Kurata, H.; Matsumoto, A.; Miki, W.; Kamiyama, M.; Itakura, H.; Yamamoto, S.; Kondo, K. Inhibition of low-density lipoprotein oxidation by astaxanthin. J. Atheroscler. Thromb. 2000, 7, 216–222.
[22]
Aflalo, C.; Meshulam, Y.; Zarka, A.; Boussiba, S. On the relative efficiency of two- vs. one-stage production of astaxanthin by the green alga Haematococcus pluvialis. Biotechnol. Bioeng. 2007, 98, 300–305, doi:10.1002/bit.21391.
[23]
Torzillo, G.; Goksan, T.; Faraloni, C.; Kopecky, J.; Masojídek, J. Interplay between photochemical activities and pigment composition in an outdoor culture of Haematococcus pluvialis during the shift from the green to red stage. J. Appl. Phycol. 2003, 15, 127–136.
[24]
Olaizola, M. Commercial production of astaxanthin from Haematococcus pluvialis using 25,000-liter outdoor photobioreactors. J. Appl. Phycol. 2000, 12, 499–506, doi:10.1023/A:1008159127672.
[25]
Wang, J.; Han, D.; Sommerfeld, M.R.; Lu, C.; Hu, Q. Effect of initial biomass density on growth and astaxanthin production of Haematococcus pluvialis in an outdoor photobioreactor. J. Appl. Phycol. 2013, 25, 253–260, doi:10.1007/s10811-012-9859-4.
[26]
Zhang, D.H.; Lee, Y.K. Enhanced accumulation of secondary carotenoids in a mutant of the green alga, Chlorococcum sp. J. Appl. Phycol. 1997, 9, 459–463, doi:10.1023/A:1007902103419.
[27]
Zhang, D.H.; Ng, M.L.; Phang, S.M. Composition and accumulation of secondary carotenoids in Chlorococcum sp. J. Appl. Phycol. 1997, 9, 147–155, doi:10.1023/A:1007926528388.
[28]
Wang, Y.; Peng, J. Growth associated biosynthesis of astaxanthin in heterotrophic Chlorella zofingiensis (Chlorophyta). World J. Microbiol. Biotechnol. 2008, 24, 1915–1922, doi:10.1007/s11274-008-9692-8.
[29]
Orosa, M.; Torres, E.; Fidalgo, P.; Abalde, J. Production and analysis of secondary carotenoids in green algae. J. Appl. Phycol. 2000, 12, 553–556, doi:10.1023/A:1008173807143.
[30]
Banerjee, K.; Ghosh, R.; Homechaudhuri, S.; Mitra, A. Biochemical composition of marine macroalgae from gangetic delta at the apex of Bay of Bengal. Afr. J. Basic Appl. Sci. 2009, 1, 96–104.
[31]
Yokoyama, A.; Adachi, K.; Shizuri, Y. New carotenoid glucosides, astaxanthin glucoside and adonimxanthin glucoside, isolated from the astaxanthin producing marine bacterium, Agrobacterium aurantiacum. J. Nat. Prod. 1995, 58, 1929–1933.
[32]
EFSA (European Food Safety Authority). Safety and efficacy of panaferd-AX(red carotenoid rich bacterium Paracoccus carotinifaciens as feed additive for salmon and trout. EFSA J. 2007, 546, 1–30.
[33]
Kim, J.H.; Kang, S.W.; Kim, S.W.; Chang, H.I. High-level production of astaxanthin by Xanthophyllomyces dendrorhous mutant JH1 using statistical experimental designs. Biosci. Biotechnol. Biochem. 2005, 69, 1743–1748, doi:10.1271/bbb.69.1743.
[34]
De la Fuente, J.L.; Rodríguez-Sáiz, M.; Schleissner, C.; Díez, B.; Peiro, E.; Barredo, J.L. High-titer production of astaxanthin by the semi-industrial fermentation of Xanthophyllomyces dendrorhous. J. Biotechnol. 2010, 148, 144–146, doi:10.1016/j.jbiotec.2010.05.004.
[35]
Yamaoka, Y. Microorganism and production of carotenoid compounds. U.S. Patent 7,374,908 B2, 20 May 2008.
[36]
Meyers, S.P.; Bligh, D. Characterization of astaxanthin pigments from heat processed crawfish waste. J. Agric. Food Chem. 1981, 3, 505–508, doi:10.1021/jf00105a017.
[37]
Foss, P.; Renstr？m, B.; Liaaen-Jensen, S. Natural occurrence of enantiomeric and meso astaxanthin. 7-crustaceans including zooplankton. Comp. Biochem. Physiol. B 1987, 86B, 313–314.
[38]
Sarada, R.; Vidhyavathi, R.; Usha, D.; Ravishankar, G.A. An efficient method for extraction of astaxanthin from green alga Haematococcus pluvialis. J. Agric. Food Chem. 2006, 54, 7585–7588.
[39]
Kobayashi, M.; Kurimura, Y.; Sakamoto, Y.; Tsuji, Y. Selective extraction of astaxanthin and chlorophyll from the green alga Haematococcus pluvialis. Biotechnol. Tech. 1997, 11, 657–660, doi:10.1023/A:1018455209445.
[40]
Mendes-Pinto, M.M.; Raposo, M.F.J.; Bowen, J.; Young, A.J.; Morais, R. Evaluation of different cell disruption processes on encysted cells of Haematococcus pluvialis: Effects on astaxanthin recovery and implications for bio-availability. J. Appl. Phycol. 2001, 13, 19–24, doi:10.1023/A:1008183429747.
[41]
Kang, C.D.; Sim, S.J. Direct extraction of astaxanthin from Haematococcus culture using vegetable oils. Biotechnol. Lett. 2008, 30, 441–444, doi:10.1007/s10529-007-9578-0.
[42]
Ni, H.; Chen, Q.H.; He, G.Q.; Wu, G.B.; Yang, Y.F. Optimization of acidic extraction of astaxanthin from Phaffia rhodozyma. J. Zhejiang Univ. Sci. B 2008, 9, 51–59.
[43]
Ruen-ngam, D.; Shotipruk, A.; Pavasant, P. Comparison of extraction methods for recovery of astaxanthin from Haematococcus pluvialis. Sep. Sci. Technol. 2010, 46, 64–70, doi:10.1080/01496395.2010.493546.
[44]
Storebakken, T.; S？rensen, M.; Bjerkeng, B.; Harris, J.; Monahan, P.; Hiu, S. Stability of astaxanthin from the red yeast, Xanthophyllomyces dendrorhous, during feed processing: Effects of enzymatic cell wall disruption and extrusion temperature. Aquaculture 2004, 231, 489–500, doi:10.1016/j.aquaculture.2003.10.034.
[45]
Machmudah, S.; Shotipruk, A.; Goto, M.; Sasaki, M.; Hirose, T. Extraction of astaxanthin from Haematococcus pluvialis using supercritical CO2 and ethanol as entrainer. Ind. Eng. Chem. Res. 2006, 45, 3652–3657, doi:10.1021/ie051357k.
[46]
Nobre, B.; Marcelo, F.; Passos, R.; Beiro, L.; Palavra, A.; Gouveia, L.; Mendes, R. Supercritical carbon dioxide extraction of astaxanthin and other carotenoids from the microalga Haematococcus pluvialis. Eur. Food Res. Technol. 2006, 223, 787–790, doi:10.1007/s00217-006-0270-8.
[47]
Wang, L.; Yang, B.; Yan, B.; Yao, X. Supercritical fluid extraction of astaxanthin from Haematococcus pluvialis and its antioxidant potential in sunflower oil. Innov. Food Sci. Emerg. Technol. 2012, 13, 120–127, doi:10.1016/j.ifset.2011.09.004.
[48]
Ranga Rao, A.; Sarada, R.; Ravishankar, G.A. Stabilization of astaxanthin in edible oils and its use as an antioxidant. J. Sci. Food Agric. 2007, 87, 957–965, doi:10.1002/jsfa.2766.
[49]
Anarjan, N.; Tan, C.P. Chemical stability of astaxanthin nanodispersions in orange juice and skimmed milk as model food systems. Food Chem. 2013, 139, 527–531, doi:10.1016/j.foodchem.2013.01.012.
[50]
Raposo, M.F.J.; Morais, A.M.M.B.; Morais, R.S.C. Effects of spray drying and storage on astaxanthin content of Haematococcus pluvialis biomass. World J. Microbiol. Biotechnol. 2012, 28, 1253–1257, doi:10.1007/s11274-011-0929-6.
[51]
Villalobos-Castillejos, F.; Cerezal-Mezquita, P.; Hemandez-De Jesus, M.L.; Barragan-Huerta, B.E. Production and stability of water-dispersible astaxanthin oleoresin from Phaffia rhodozyma. Int. J. Food Sci. Technol. 2013, 48, 1243–1251, doi:10.1111/ijfs.12083.
[52]
Yuan, C.; Du, L.; Jin, Z.; Xu, X. Storage stability and antioxidant activity of complex of astaxanthin with hydroxypropyl-β-cyclodextrin. Carbohydr. Polym. 2013, 91, 385–389, doi:10.1016/j.carbpol.2012.08.059.
[53]
Higuera-Ciapara, I.; Felix-Valenzuela, L.; Goycoolea, F.M.; Arguelles-Monal, W. Microencapsulation of astaxanthin in a chitosan matrix. Carbohydr. Polym. 2004, 56, 41–45, doi:10.1016/j.carbpol.2003.11.012.
[54]
Tachaprutinun, A.; Udomsup, T.; Luadthong, C.; Wanichwecharungruang, S. Preventing the thermal degradation of astaxanthin through nanoencapsulation. Int. J. Pharm. 2009, 374, 119–124, doi:10.1016/j.ijpharm.2009.03.001.
[55]
Ribeiro, H.S.; Rico, L.G.; Badolato, G.G.; Schubert, H. Production of O/W emulsions containing astaxanthin by repeated premix membrane emulsification. J. Food Sci. 2005, 70, E117–E123.
[56]
Chen, X.; Chen, R.; Guo, Z.; Li, C.; Li, P. The preparation and stability of the inclusion complex of astaxanthin with β-cyclodextrin. Food Chem. 2007, 101, 1580–1584, doi:10.1016/j.foodchem.2006.04.020.
[57]
Barros, M.P.; Marin, D.P.; Bolin, A.P.; de Cássia Santos Macedo, R.; Campoio, T.R.; Fineto, C., Jr.; Guerra, B.A.; Polotow, T.G.; Vardaris, C.; Mattei, R.; et al. Combined astaxanthin and fish oil supplementation improves glutathione-based redox balance in rat plasma and neutrophils. Chem. Biol. Interact. 2012, 197, 58–67, doi:10.1016/j.cbi.2012.03.005.
[58]
Otton, R.; Marin, D.P.; Bolin, A.P.; de Cássia Santos Macedo, R.; Campoio, T.R.; Fineto, C.J.; Guerra, B.A.; Leite, J.R.; Barros, M.P.; Mattei, R. Combined fish oil and astaxanthin supplementation modulates rat lymphocyte function. Eur. J. Nutr. 2012, 51, 707–718, doi:10.1007/s00394-011-0250-z.
[59]
Page, G.I.; Davies, S.J. Astaxanthin and canthaxanthin do not induce liver or kidney xenobiotic-metabolizing enzymes in rainbow trout (Oncorhynchus mykiss Walbaum). Comp. Biochem. Physiol. C Toxicol. Pharmacol. 2002, 133C, 443–451, doi:10.1016/S1532-0456(02)00168-0.
[60]
Osterlie, M.; Bjerkeng, B.; Liaaen-Jensen, S. Plasma appearance and distribution of astaxanthin E/Z isomers in plasma lipoproteins of after single dose administration of astaxanthin. J. Nutr. Biochem. 2000, 11, 482–492, doi:10.1016/S0955-2863(00)00104-2.
[61]
Okada, Y.; Ishikura, M.; Maoka, T. Bioavailability of astaxanthin in Haematococcus algal extract: the effects of timing of diet and smoking habits. Biosci. Biotechnol. Biochem. 2009, 73, 1928–1932, doi:10.1271/bbb.90078.
[62]
Olson, J.A. Carotenoids: absorption, transport, and metabolism of carotenoids in humans. Pure Appl. Chem. 2004, 66, 1011–1016, doi:10.1351/pac199466051011.
[63]
Naguib, Y.M.A. Antioxidant activities of astaxanthin and related carotenoids. J. Agric. Food Chem. 2000, 48, 1150–1154, doi:10.1021/jf991106k.
[64]
Liu, X.; Osawa, T. Cis astaxanthin and especially 9-cis astaxanthin exhibits a higher antioxidant activity in vitro compared to the all trans isomer. Biochem. Biophys. Res. Commun. 2007, 357, 187–193, doi:10.1016/j.bbrc.2007.03.120.
[65]
Miki, W. Biological functions and activities of animal carotenoids. Pure Appl. Chem. 1991, 63, 141–146, doi:10.1351/pac199163010141.
[66]
Martin, H.D.; Jager, C.; Ruck, C.; Schmidt, M. Anti and pro-oxidant properties of carotenoids. J. Prakt. Chem. 1999, 341, 302–308, doi:10.1002/(SICI)1521-3897(199904)341:3<302::AID-PRAC302>3.0.CO;2-6.
[67]
Augusti, P.R.; Quatrin, A.; Somacal, S.; Conterato, G.M.; Sobieskim, R.; Ruviaro, A.R.; Maurer, L.H.; Duarte, M.M.; Roehrs, M.; Emanuelli, T. Astaxanthin prevents changes in the activities of thioredoxin reductase and paraoxonase in hypercholesterolemic rabbits. J. Clin. Biochem. Nutr. 2012, 51, 42–49, doi:10.3164/jcbn.11-74.
[68]
Kamath, B.S.; Srikanta, B.M.; Dharmesh, S.M.; Sarada, R.; Ravishankar, G.A. Ulcer preventive and antioxidative properties of astaxanthin from Haematococcus pluvialis. Eur. J. Pharmacol. 2008, 590, 387–395, doi:10.1016/j.ejphar.2008.06.042.
[69]
Goto, S.; Kogure, K.; Abe, K.; Kimata, Y.; Yamashita, E.; Terada, H. Efficient radical trapping at the surface and inside the phospholipid membrane is responsible for highly potent antiperoxidative activity of the carotenoid astaxanthin. Biochim. Biophys. Acta 2001, 1512, 251–258.
[70]
Liu, B.H.; Lee, Y.K. Effect of total secondary carotenoids extracts from Chlorococcum sp. on Helicobacter pylori infected BALB/c mice. Int. Immunopharmacol. 2003, 3, 979–986, doi:10.1016/S1567-5769(03)00096-1.
[71]
Bennedsen, M.; Wang, X.; Willen, R.; Wadstrom, T.; Andersen, L.P. Treatment of H. pylori infected mice with antioxidant astaxanthin reduces gastric inflammation, bacterial load and modulates cytokine release by splenocytes. Immunol. Lett. 1999, 70, 185–189.
[72]
Park, J.S.; Chyun, J.H.; Kim, Y.K.; Line, L.L.; Chew, B.P. Astaxanthin decreased oxidative stress and inflammation and enhanced immune response in humans. Nutr. Metab. 2010, 7, 1–10.
[73]
Haines, D.D.; Varga, B.; Bak, I.; Juhasz, B.; Mahmoud, F.F; Kalantari, H.; Gesztelyi, R.; Lekli, I.; Czompa, A.; Tosaki, A. Summative interaction between astaxanthin, Ginkgo biloba extract (EGb761) and vitamin C in suppression of respiratory inflammation: A comparison with ibuprofen. Phytother. Res. 2011, 25, 128–136, doi:10.1002/ptr.3160.
[74]
Ohgami, K.; Shiratori, K.; Kotake, S.; Nishida, T.; Mizuki, N.; Yazawa, K.; Ohno, S. Effects of astaxanthin on lipopolysaccharide-induced inflammation in vitro and in vivo. Invest. Ophthalmol. Vis. Sci. 2003, 44, 2694–2701, doi:10.1167/iovs.02-0822.
[75]
Suzuki, Y.; Ohgami, K.; Shiratori, K.; Jin, X.H.; Llieva, I.; Koyama, Y.; Yazawa, K.; Yoshidia, K.; Kase, S.; Ohno, S. Suppressive effects of astaxanthin against rat endotoxin induced uveitis by inhibiting the NF-kB signaling pathway. Exp. Eye Res. 2006, 82, 275–281, doi:10.1016/j.exer.2005.06.023.
[76]
Hama, S.; Takahashi, K.; Inai, Y.; Shiota, K.; Sakamoto, R.; Yamada, A.; Tsuchiya, H.; Kanamura, K.; Yamashita, E.; Kogure, K. Protective effects of topical application of a poorly soluble antioxidant astaxanthin liposomal formulation on ultraviolet-induced skin damage. J. Pharm. Sci. 2012, 101, 2909–2916, doi:10.1002/jps.23216.
[77]
Santos, S.D.; Cahú, T.B.; Firmino, G.O.; de Castro, C.C.; Carvalho, L.B.J.; Bezerra, R.S.; Filho, J.L. Shrimp waste extract and astaxanthin: Rat alveolar macrophage, oxidative stress and inflammation. J. Food Sci. 2012, 77, 141–146.
[78]
Uchiyama, K.; Naito, Y.; Hasegawa, G.; Nakamura, N.; Takahashi, J.; Yoshikawa, T. Astaxanthin protects β-cells against glucose toxicity in diabetic db/db mice. Redox Rep. 2002, 7, 290–293, doi:10.1179/135100002125000811.
[79]
Otton, R.; Marin, D.P.; Bolin, A.P.; Santos, R.C.; Polotow, T.G.; Sampaio, S.C.; De Barros, M.P. Astaxanthin ameliorates the redox imbalance in lymphocytes of experimental diabetic rats. Chem. Biol. Interact. 2010, 186, 306–315, doi:10.1016/j.cbi.2010.05.011.
[80]
Nakano, M.; Onodera, A.; Saito, E.; Tanabe, M.; Yajima, K.; Takahashi, J.; Nguyen, V.C. Effect of astaxanthin in combination with α-tocopherol or ascorbic acid against oxidative damage in diabetic ODS rats. J. Nutr. Sci. Vitaminol. 2008, 54, 329–334, doi:10.3177/jnsv.54.329.
[81]
Nishigaki, I.; Rajendran, P.; Venugopal, R.; Ekambaram, G.; Sakthisekaran, D.; Nishigaki, Y. Cytoprotective role of astaxanthin against glycated protein/iron chelate-induced toxicity in human umbilical vein endothelial cells. Phytother. Res. 2010, 24, 54–59, doi:10.1002/ptr.2867.
[82]
Hussein, G.; Nakagawa, T.; Goto, H.; Shimada, Y.; Matsumoto, K.; Sankawa, U.; Watanabe, H. Astaxanthin ameliorates features of metabolic syndrome in SHR/NDmcr-cp. Life Sci. 2007, 80, 522–529, doi:10.1016/j.lfs.2006.09.041.
[83]
Bhuvaneswari, S.; Arunkumar, E.; Viswanathan, P.; Anuradha, C.V. Astaxanthin restricts weight gain, promotes insulin sensitivity and curtails fatty liver disease in mice fed an obesity-promoting diet. Process Biochem. 2010, 45, 1406–1414, doi:10.1016/j.procbio.2010.05.016.
[84]
Bhuvaneswari, S.; Yogalakshmi, B.; Sreeja, S.; Anuradha, C.V. Astaxanthin reduces hepatic endoplasmic reticulum stress and nuclear factor-κB-mediated inflammation in high fructose and high fat diet-fed mice. Cell Stress Chaperones 2013. in press.
[85]
Naito, Y.; Uchiyama, K.; Aoi, W.; Hasegawa, G.; Nakamura, N.; Yoshida, N.; Maoka, T.; Takahashi, J.; Yoshikawa, T. Prevention of diabetic nephropathy by treatment with astaxanthin in diabetic db/db mice. BioFactors 2004, 20, 49–59, doi:10.1002/biof.5520200105.
[86]
Kim, Y.J.; Kim, Y.A.; Yokozawa, T. Protection against oxidative stress, inflammation, and apoptosis of high glucose- exposed proximal tubular epithelial cells by astaxanthin. J. Agric. Food Chem. 2009, 57, 8793–8797, doi:10.1021/jf9019745.
Khan, S.K.; Malinski, T.; Mason, R.P.; Kubant, R.; Jacob, R.F.; Fujioka, K.; Denstaedt, S.J.; King, T.J.; Jackson, H.L.; Hieber, A.D.; et al. Novel astaxanthin prodrug (CDX-085) attenuates thrombosis in a mouse model. Thromb. Res. 2010, 126, 299–305, doi:10.1016/j.thromres.2010.07.003.
[94]
Nakao, R.; Nelson, O.L.; Park, J.S.; Mathison, B.D.; Thompson, P.A.; Chew, B.P. Effect of astaxanthin supplementation on inflammation and cardiac function in BALB/c mice. Anticancer Res. 2010, 30, 2721–2725.
[95]
Ryu, S.K.; King, T.J.; Fujioka, K.; Pattison, J.; Pashkow, F.J.; Tsimikas, S. Effect of an oral astaxanthin prodrug (CDX-085) on lipoprotein levels and progression of atherosclerosis in LDLR and ApoE mice. Atherosclerosis 2012, 222, 99–105, doi:10.1016/j.atherosclerosis.2012.02.002.
[96]
Wolf, G. Retinoids and carotenoids as inhibitors of carcinogenesis and inducers of cell-cell communication. Nutr. Rev. 1992, 50, 270–274, doi:10.1111/j.1753-4887.1992.tb01345.x.
[97]
Hanusch, M.; Stahl, W.; Schulz, W.A.; Sies, H. Induction of gap junctional communication by 4-oxoretinoic acid generated from its precursor canthaxanthin. Arch. Biochem. Biophys. 1995, 317, 423–428, doi:10.1006/abbi.1995.1184.
[98]
Hix, L.M.; Lockwood, S.F.; Bertram, J.S. Upregulation of connexin 43 protein expression and increased gap junctional communication by water soluble disodium disuccinate astaxanthin derivatives. Cancer Lett. 2006, 211, 25–37.
[99]
Daubrawa, F.; Sies, H.; Stahl, W. Astaxanthin diminishes gap junctional intercellular communication in primary human fibroblasts. J. Nutr. 2005, 135, 2507–2511.
[100]
Zhang, L.X.; Cooney, R.V.; Bertram, J.S. Carotenoids enhance gap junctional communication and inhibit lipid peroxidation in C3H/10T1/2 cells: relationship to their cancer chemopreventive action. Carcinogenesis 1991, 12, 2109–2114, doi:10.1093/carcin/12.11.2109.
[101]
Zhang, L.X.; Cooney, R.V.; Bertram, J.S. Carotenoids up-regulate connexin-43 gene expression independent of their provitamin A or antioxidant properties. Cancer Res. 1992, 52, 5707–5712.
[102]
Chew, B.P.; Park, J.S. Carotenoid action on the immune response. J. Nutr. 2004, 134, 257S–261S.
[103]
Chew, B.P.; Park, J.S.; Wong, M.W.; Wong, T.S. A comparison of the anticancer activities of dietary β-carotene, canthaxanthin and astaxanthin in mice in vivo. Anticancer Res. 1999, 19, 1849–1853.
[104]
Palozza, P.; Torelli, C.; Boninsegna, A.; Simone, R.; Catalano, A.; Mele, M.C.; Picci, N. Growth-inhibitory effects of the astaxanthin-rich alga Haematococcus pluvialis in human colon cancer cells. Cancer Lett. 2009, 283, 108–117, doi:10.1016/j.canlet.2009.03.031.
[105]
Tanaka, T.; Makita, H.; Ohnishi, M.; Mori, H.; Satoh, K.; Hara, A. Chemoprevention of rat oral carcinogenesis by naturally occurring xanthophyll’s, astaxanthin and canthaxanthin. Cancer Res. 1995, 55, 4059–4064.
[106]
Tanaka, T.; Morishita, Y.; Suzui, M.; Kojima, T.; Okumura, A.; Mori, H. Chemoprevention of mouse urinary bladder carcinogenesis by the naturally occurring carotenoid astaxanthin. Carcinogenesis 1994, 15, 15–19, doi:10.1093/carcin/15.1.15.
[107]
Jyonouchi, H.; Sun, S.; Iijima, K.; Gross, M.D. Antitumor activity of astaxanthin and its mode of action. Nutr. Cancer 2000, 36, 59–65, doi:10.1207/S15327914NC3601_9.
[108]
Prabhu, P.N.; Ashokkumar, P.; Sudhandiran, G. Antioxidative and anti-proliferative effects of astaxanthin during the initiation stages of 1,2-dimethyl hydrazineinduced experimental colon carcinogenesis. Fund. Clin. Pharmacol. 2009, 23, 225–234, doi:10.1111/j.1472-8206.2009.00669.x.
[109]
Nakao, R.; Nelson, O.L.; Park, J.S.; Mathison, B.D.; Thompson, P.A.; Chew, B.P. Effect of dietary astaxanthin at different stages of mammary tumor initiation in BALB/c mice. Anticancer Res. 2010, 30, 2171–2175.
[110]
Maoka, T.; Tokuda, H.; Suzuki, N.; Kato, H.; Etoh, H. Anti-oxidative, anti-tumor-promoting, and anti-carcinogenesis activities of nitroastaxanthin and nitrolutein, the reaction products of astaxanthin and lutein with peroxynitrite. Mar. Drugs 2012, 10, 1391–1399, doi:10.3390/md10061391.
[111]
Jyonouchi, H.; Hill, R.; Tomita, Y.; Good, R. Studies of immunomodulating actions of carotenoids. I. Effects of β-carotene and astaxanthin on murine lymphocyte functions and cell surface marker expression in in vitro culture system. Nutr. Cancer 1991, 16, 93–105, doi:10.1080/01635589109514148.
[112]
Jyonouchi, H.; Zhang, L.; Gross, M.; Tomita, Y. Immunomodulating actions of carotenoids: Enhancement of in vivo and in vitro antibody production to T-dependent antigens. Nutr. Cancer 1994, 21, 47–58, doi:10.1080/01635589409514303.
[113]
Jyonouchi, H.; Sun, S.; Gross, M. Effect of carotenoids on in vitro immunoglobulin production by human peripheral blood mononuclear cells: astaxanthin, a carotenoid without vitamin A activity, enhances in vitro immunoglobulin production in response to a T-dependent stimulant and antigen. Nutr. Cancer 1995, 23, 171–183, doi:10.1080/01635589509514373.
[114]
Park, J.S.; Mathison, B.D.; Hayek, M.G.; Massimino, S.; Reinhart, G.A.; Chew, B.P. Astaxanthin stimulates cell-mediated and humoral immune responses in cats. Vet. Immunol. Immunopathol. 2011, 144, 455–461, doi:10.1016/j.vetimm.2011.08.019.
[115]
Choi, H.D.; Kang, H.E.; Yang, S.H.; Lee, M.G.; Shin, W.G. Pharmacokinetics and first-pass metabolism of astaxanthin in rats. Br. J. Nutr. 2011, 105, 220–227, doi:10.1017/S0007114510003454.
[116]
Sila, A.; Ayed-Ajmi, Y.; Sayari, N.; Nasri, M.; Martinez-Alvarez, O.; Bougatef, A. Antioxidant and anti-proliferative activities of astaxanthin extracted from the shell waste of deep-water pink shrimp (Parapenaeus longirostris). Nat. Prod. J. 2013, 3, 82–89.
[117]
Kim, J.H.; Chang, M.J.; Choi, H.D.; Youn, Y.K.; Kim, J.T.; Oh, J.M.; Shin, W.G. Protective effects of Haematococcus astaxanthin on oxidative stress in healthy smokers. J. Med. Food 2011, 14, 1469–1475, doi:10.1089/jmf.2011.1626.
[118]
Nakagawa, K.; Kiko, T.; Miyazawa, T.; Carpentero Burdeos, G.; Kimura, F.; Satoh, A.; Miyazawa, T. Antioxidant effect of astaxanthin on phospholipid peroxidation in human erythrocytes. Br. J. Nutr. 2011, 105, 1563–1571, doi:10.1017/S0007114510005398.
[119]
Yang, Y.; Seo, J.M.; Nguyen, A.; Pham, T.X.; Park, H.J.; Park, Y.; Kim, B.; Bruno, R.S.; Lee, J. Astaxanthin-rich extract from the green alga Haematococcus pluvialis lowers plasma lipid concentrations and enhances antioxidant defense in apolipoprotein E knockout mice. J. Nutr. 2011, 141, 1611–1617, doi:10.3945/jn.111.142109.
[120]
Ishiki, M.; Nishida, Y.; Ishibashi, H.; Wada, T.; Fujisaka, S.; Takikawa, A.; Urakaze, M.; Sasaoka, T.; Usui, I.; Tobe, K. Impact of divergent effects of astaxanthin on insulin signaling in l6 cells. Endocrinology 2013, 154, 2600–2612, doi:10.1210/en.2012-2198.
[121]
Huangfu, J.; Liu, J.; Sun, Z.; Wang, M.; Jiang, Y.; Chen, Z.Y.; Chen, F. Anti-ageing effects of astaxanthin-rich alga Haematococcus pluvialis on fruit flies under oxidative stress. J. Agric. Food Chem. 2013, 6, 7800–7804.
[122]
Chew, W.; Mathison, B.D.; Kimble, L.L.; Mixter, P.F.; Chew, B.P. Astaxanthin decreases inflammatory biomarkers associated with cardiovascular disease in human umbilical vein endothelial cells. Am. J. Adv. Food Sci. Technol. 2013, 1, 1–17.
[123]
Park, J.S.; Mathison, B.D.; Hayek, M.G.; Zhang, J.; Reinhart, G.A.; Chew, B.P. Astaxanthin modulates age-associated mitochondrial dysfunction in healthy dogs. J. Animal Sci. 2013, 91, 268–275, doi:10.2527/jas.2012-5341.
[124]
Gal, A.F.; Andrei, S.; Cernea, C.; Taulescu, M.; Catoi, C. Effects of astaxanthin supplementation on chemically induced tumorigenesis in Wistar rats. Acta Vet. Scand. 2012, 54, 1–6, doi:10.1186/1751-0147-54-1.
[125]
Wibrand, K.; Berge, K.; Messaoudi, M.; Duffaud, A.; Panja, D.; Bramham, C.R.; Burri, L. Enhanced cognitive function and antidepressant-like effects after krill oil supplementation in rats. Lipids Health Dis. 2013, 12, 1–13, doi:10.1186/1476-511X-12-1.
[126]
Turkez, H.; Geyikoglu, F.; Yousef, M.I. Beneficial effect of astaxanthin on 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced liver injury in rats. Toxicol. Ind. Health 2012, 29, 591–599, doi:10.1177/0748233711434959.
[127]
Chan, K.C.; Pen, P.J.; Yin, M.C. Anti-coagulatory and anti-inflammatory effects of astaxanthin in diabetic rats. J. Food Sci. 2012, 77, H76–H80, doi:10.1111/j.1750-3841.2011.02558.x.
[128]
Dong, L.Y.; Jin, J.; Lu, G.; Kang, X.L. Astaxanthin attenuates the apoptosis of retinal ganglion cells in db/db mice by inhibition of oxidative stress. Mar. Drugs 2013, 11, 960–974, doi:10.3390/md11030960.
[129]
Iizuka, M.; Ayaori, M.; Uto-Kondo, H.; Yakushiji, E.; Takiguchi, S.; Nakaya, K.; Hisada, T.; Sasaki, M.; Komatsu, T.; Yogo, M.; et al. Astaxanthin enhances ATP-binding cassette transporter A1/G1 expressions and cholesterol efflux from macrophages. J. Nutr. Sci. Vitaminol. (Tokyo) 2012, 58, 96–104, doi:10.3177/jnsv.58.96.
[130]
Yoshida, H.; Yanai, H.; Ito, K.; Tomono, Y.; Koikeda, T.; Tsukahara, H.; Tada, N. Administration of natural astaxanthin increases serum HDL-cholesterol and adiponectin in subjects with mild hyperlipidemia. Atherosclerosis 2010, 209, 520–523, doi:10.1016/j.atherosclerosis.2009.10.012.
[131]
Chang, C.H.; Chen, C.Y.; Chiou, J.Y.; Peng, R.Y.; Peng, C.H. Astaxanthin secured apoptic death of PC12 cells induced by β-amyloid peptide 25–35: Its molecular action targets. J. Med. Food 2010, 13, 548–556, doi:10.1089/jmf.2009.1291.
[132]
Lu, Y.P.; Liu, S.Y.; Sun, H.; Wu, X.M.; Li, J.J.; Zhu, L. Neuroprotective effect of astaxanthin on H2O2-induced neurotoxicity in vitro and on focal cerebral ischemia in vivo. Brain Res. 2010, 1360, 40–48.
Hussein, G.; Nakamura, M.; Zhao, Q.; Iguchi, T.; Goto, H.; Sankawa, U.; Watanabe, H. Antihypertensive and neuroprotective effects of astaxanthin in experimental animals. Biol. Pharm. Bull. 2005, 28, 47–52, doi:10.1248/bpb.28.47.
[135]
Kim, J.H.; Kim, Y.S.; Song, G.G.; Park, J.J.; Chang, H.I. Protective effect of astaxanthin on naproxen-induced gastric antral ulceration in rats. Eur. J. Pharmacol. 2005, 514, 53–59, doi:10.1016/j.ejphar.2005.03.034.
[136]
Petri, D.; Lundebye, A.K. Tissue distribution of astaxanthin in rats following exposure to graded levels in the feed. Comp. Biochem. Physiol. C Toxicol. Pharmacol. 2007, 145, 202–209, doi:10.1016/j.cbpc.2006.12.008.
[137]
Murata, K.; Oyagi, A.; Takahira, D.; Tsuruma, K.; Shimazawa, M.; Ishibashi, T.; Hara, H. Protective effects of astaxanthin from paracoccus carotinifaciens on murine gastric ulcer models. Phytother. Res. 2012, 26, 1126–1132, doi:10.1002/ptr.3681.
[138]
Odeberg, M.J.; Lignell, A.; Pettersson, A.; Hoglund, P. Oral bioavailability of the antioxidant astaxanthin in humans is enhanced by incorporation of lipid based formulations. Eur. J. Pharm. Sci. 2003, 19, 299–304, doi:10.1016/S0928-0987(03)00135-0.
[139]
Serebruany, V.; Malinin, A.; Goodin, T.; Pashkow, F. The in vitro effects of xancor, a synthetic astaxanthine derivative, on hemostatic biomarkers in aspirin-naive and aspirin-treated subjects with multiple risk factors for vascular disease. Am. J. Ther. 2010, 17, 125–132, doi:10.1097/MJT.0b013e31819cdbbd.
[140]
Spiller, G.A.; Dewell, A. Safety of an astaxanthin rich Haemaotoccu pluvialis algal extract: A randomized clinical trial. J. Med. Food 2003, 6, 51–56, doi:10.1089/109662003765184741.
[141]
Miyawaki, H.; Takahashi, J.; Tsukahara, H.; Takehara, I. Effects of astaxanthin on human blood rheology. J. Clin. Biochem. Nutr. 2008, 43, 69–74, doi:10.3164/jcbn.2008048.
[142]
Karppi, J.; Rissanen, T.H.; Nyyssonen, K.; Kaikkonen, J.; Olsson, A.G.; Voutilainen, S.; Salonen, J.T. Effects of astaxanthin supplementation on lipid peroxidation. Int. J. Vitam. Nutr. Res. 2007, 77, 3–11, doi:10.1024/0300-9831.77.1.3.
[143]
Parisi, V.; Tedeschi, M.; Gallinaro, G.; Varano, M.; Saviano, S.; Piermarocchi, S. Carotenoids and antioxidants in age-related maculopathy italian study: multifocal electroretinogram modifications after one year. Ophthalmology 2008, 115, 324–333, doi:10.1016/j.ophtha.2007.05.029.
[144]
Katagiri, M.; Satoh, A.; Tsuji, S.; Shirasawa, T. Effects of astaxanthin rich Haematococcus pluvialis extact on cognitive function: Arandomised double blind, placebo-controlled study. J. Clin. Biochem. Nutr. 2012, 51, 102–107, doi:10.3164/jcbn.D-11-00017.
[145]
Tominaga, K.; Hongo, N.; Karato, M.; Yamashita, E. Cosmetic benefits of astaxanthin on humans subjects. Acta Biochim. Pol. 2012, 59, 43–47.
[146]
Hashimoto, H.; Arai, K.; Hayashi, S.; Okamoto, H.; Takahashi, J.; Chikuda, M.; Obara, Y. Effects of astaxanthin on antioxidation in human aqueous humor. J. Clin. Biochem. Nutr. 2013, 53, 1–7, doi:10.3164/jcbn.13-6.
[147]
Chew, B.P.; Park, J.S. Natural astaxanthin extract reduces DNA oxidation. Patent US20060217445, 28 September 2006.
[148]
Tsuji, S.; Shirasawa, T.; Shimizu, T. Neurocyte protective agent. Patent US20070293568, 23 December 2007.
[149]
Leigh, S.; Steven Leight, M.L.; Hogevest, P.V. Crystal forms of astaxanthin. Patent US20080234521, 25 September 2007.
[150]
Lockwood, S.F.; Preston, M. Use of carotenoids and or carotenoid derivatives analogs for reduction/inhibition of certain negative effects of COX inhibitors. Patent US20080293679, 27 November 2008.
[151]
Takahashi, J.; Yamashita, E.; Fukamauchi, M.; Tanka, I. Composition for body fat reduction. Patent US20090047304, 8 June 2009.
[152]
Sharoni, Y.; Levy, J.; Sela, Y.; Nir, Z. Carotenoid oxidation products as chemo preventive and chemotherapeutic agents. Patent US20090069417, 12 March 2009.
[153]
Senin, P.; Setnikar, I.; Rovati, A. Formulation for oral administration with beneficial effects on the cardiovascular system. U.S. Patent 20090136469, 28 May 2009.
[154]
David, A.E.; Melchior, R. Algal and algal extract dietary supplement composition. Patent US20090142431, 4 June 2009.
[155]
Satoh, A.; Tsuji, S. Method for improving cognitive performance. Patent US20090297492, 3 December 2009.
[156]
Qvyjt, F. Encapsulates. Patent US20100158984, 24 June 2010.
[157]
Tominaga, K.; Karato, M.; Hongo, N.; Yamashita, E. Method of preventing discoloration of carotenoid pigment and container used therefor. Patent US20100204523, 12 August 2010.
[158]
Kopsel, C. Pulverulent carotenoid preparation for colouring drinks. Patent US20100267838, 21 October 2010.
[159]
Clayton, D.; Rutter, R. Inflammatory disease treatment. Patent US20100291053, 18 November 2010.
[160]
Higashi, N.; Takahashi, J. Agent for alleviating vascular failure. Patent US20120004297, 5 Jannuary 2012.
[161]
Koppe, W.M.; Moeller, N.P.; Baardsen, G.K.L. Feed additive for improved pigment retention. Patent US20120114823, 10 May 2012.
[162]
Jouni, Z.; Makhoul, Z. Carotenoid containing compositions and methods. Patent US20120238522, 20 September 2012.
[163]
Monahan, P.; Hiu, S. Agent for improving carcass performance in finishing hogs. Patent US20120253078, 4 October 2012.
[164]
Minatelli, J.A.; Thomas, S.; Rajendran, L.; Moerck, E. Composition and method to alleviate joint pain. Patent US20130004582, 3 January 2013.
[165]
Ooi, Y.; Kitamura, A.; Yamashita, E. Baked food produced from astaxanthin containing dough. Patent US 20130108764, 2 May 2013.
