Microalgal carotenoids: Beneficial effects and potential in human health

Food and Function

Volumn 5, Issue 3, 2014, Pages 413-425

  Zhang, Jie ^a   Sun, Zheng ^b,c   Sun, Peipei ^a,d   Chen, Tianpeng ^a   Chen, Feng ^a  

^a PEKING UNIVERSITY   (China)

^b SHANGHAI OCEAN UNIVERSITY   (China)

^c CITY UNIVERSITY OF HONG KONG   (Hong Kong)

^d SOUTH CHINA UNIVERSITY OF TECHNOLOGY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

ALGAE; MICROORGANISMS;

ANTI-INFLAMMATORY EFFECTS; ASTAXANTHIN; BENEFICIAL EFFECTS; HEALTH BENEFITS; HUMAN HEALTH; KETOCAROTENOIDS; MICRO-ALGAE; NATURAL SOURCES;

PIGMENTS;

ANTIINFLAMMATORY AGENT; ANTIOXIDANT; CAROTENOID;

CHEMISTRY; HEALTH FOOD; HUMAN; MICROALGA; REVIEW;

ANTI-INFLAMMATORY AGENTS; ANTIOXIDANTS; CAROTENOIDS; HEALTH FOOD; HUMANS; MICROALGAE;

EID: 84896841068     PISSN: 20426496     EISSN: 2042650X     Source Type: Journal    
DOI: 10.1039/c3fo60607d     Document Type: Review

References (152)

1. BCC Research, FODO25D-The global market for carotenoids, Wellesley, MA, 2011, http://www.bccresearch.com/report/carotenoids-global-market-fod025d.html, accessed 30 January 2013, accessed 10 March 2013
2. F. Chen and Y. Jiang, Biotechnology of microalgae, China Light industry Press, Beijing, 1999
3. E. Jacob-Lopes C. H. G. Scoparo T. T. Franco Rates of CO2 removal by Aphanothece microscopica Nägeli in tubular photobioreactors Chem. Eng. Process. 2008 47 1365 1373
4. T. L. Chacón-Lee G. E. González-Mariño Microalgae for "healthy" foods-possibilities and challenges Compr. Rev. Food Sci. Food Saf. 2010 9 655 675
5. M. Plaza S. Santoyo L. Jaime G. García-Blairsy Reina M. Herrero F. J. Señoráns E. Ibáñez Screening for bioactive compounds from algae J. Pharm. Biomed. Anal. 2010 51 450 455
6. M. F. J. Raposo R. M. S. C. Morais A. M. M. B. Morais Health applications of bioactive compounds from marine microalgae Life Sci. 2013 93 479 486
7. J. Peng J. P. Yuan C. F. Wu J. H. Wang Fucoxanthin, a marine carotenoid present in brown seaweeds and diatoms: metabolism and bioactivities relevant to human health Mar. Drugs 2011 9 1806 1828
8. X. M. Shi F. Chen J. P. Yuan H. Chen Heterotrophic production of lutein by selected Chlorella strains J. Appl. Phycol. 1997 9 445 450
9. F. Chen High cell density culture of microalgae in heterotrophic growth Trends Biotechnol. 1996 14 421 426
10. P. F. Ip F. Chen Production of astaxanthin by the green microalga Chlorella zofingiensis in the dark Process Biochem. 2005 40 733 738
11. H. B. Li K. W. Fan F. Chen Isolation and purification of canthaxanthin from the microalga Chlorella zofingiensis by high-speed counter-current chromatography J. Sep. Sci. 2006 29 699 703
12. M. Rise E. Cohen M. Vishkautsan M. Cojocaru H. E. Gottlieb S. M. Arad Accumulation of Secondary Carotenoids in Chlorella zofingiensis J. Plant Physiol. 1994 144 287 292
13. M. Orosa E. Torres P. Fidalgo J. Abalde Production and analysis of secondary carotenoids in green algae J. Appl. Phycol. 2000 12 553 556
14. S. Takaichi Carotenoids in algae: distributions, biosyntheses and functions Mar. Drugs 2011 9 1101 1118
15. F. X. Cunningham Jr E. Gantt Elucidation of the Pathway to Astaxanthin in the Flowers of Adonis aestivalis Plant Cell 2011 23 3055 3069
16. R. Willstätter H. J. Page Chlorophyll. XXIV. The pigments of the brown algae Eur. J. Org. Chem. 1914 404 237 271
17. F. J. Pashkow D. G. Watumull C. L. Campbell Astaxanthin: a novel potential treatment for oxidative stress and inflammation in cardiovascular disease Am. J. Cardiol. 2008 101 58D 68D
18. J. P. Yuan J. Peng K. Yin J. H. Wang Potential health-promoting effects of astaxanthin: a high-value carotenoid mostly from microalgae Mol. Nutr. Food Res. 2011 55 150 165
19. M. Valko D. Leibfritz J. Moncol M. T. D. Cronin M. Mazur J. Telser Free radicals and antioxidants in normal physiological functions and human disease Int. J. Biochem. Cell Biol. 2007 39 44 84
20. H. D. Martin C. Jäger C. Ruck M. Schmidt R. Walsh J. Paust Anti-and Prooxidant Properties of Carotenoids J. Prakt. Chem. 1999 341 302 308
21. G. W. Burton K. Ingold Beta-carotene: an unusual type of lipid antioxidant Science 1984 224 569 573
22. C. A. Rice-Evans J. Sampson P. M. Bramley D. E. Holloway Why do we expect carotenoids to be antioxidants in vivo? Free Radical Res. 1997 26 381 398
23. S. A. R. Paiva R. M. Russell β-carotene and other carotenoids as antioxidants J. Am. Coll. Nutr. 1999 18 426 433
24. L. H. Skibsted Carotenoids in antioxidant networks. Colorants or radical scavengers J. Agric. Food Chem. 2012 60 2409 2417
25. A. A. Woodall G. Britton M. J. Jackson Antioxidant activity of carotenoids in phosphatidylcholine vesicles: chemical and structural considerations Biochem. Soc. Trans. 1995 23 133S
26. W. G. Roberts M. H. Gordon Determination of the total antioxidant activity of fruits and vegetables by a liposome assay J. Agric. Food Chem. 2003 51 1486 1493
27. E. Rodrigues L. R. B. Mariutti A. Z. Mercadante Scavenging Capacity of Marine Carotenoids against Reactive Oxygen and Nitrogen Species in a Membrane-Mimicking System Mar. Drugs 2012 10 1784 1798
28. W. Miki Biological functions and activities of animal carotenoids Pure Appl. Chem. 1991 63 141 146
29. G. Hussein U. Sankawa H. Goto K. Matsumoto H. Watanabe Astaxanthin, a Carotenoid with Potential in Human Health and Nutrition J. Nat. Prod. 2006 69 443 449
30. A. Ranga Rao R. L. Raghunath Reddy V. Baskaran R. Sarada G. A. Ravishankar 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
31. S. Goto K. Kogure K. Abe Y. Kimata K. Kitahama E. Yamashita H. Terada 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, Biomembr. 2001 1512 251 258
32. H. P. McNulty J. Byun S. F. Lockwood R. F. Jacob R. P. Mason Differential effects of carotenoids on lipid peroxidation due to membrane interactions: X-ray diffraction analysis Biochim. Biophys. Acta, Biomembr. 2007 1768 167 174
33. R. G. Fassett J. S. Coombes Astaxanthin in Cardiovascular Health and Disease Molecules 2012 17 2030 2048
34. R. Medzhitov Origin and physiological roles of inflammation Nature 2008 454 428 435
35. P. Libby Inflammatory mechanisms: the molecular basis of inflammation and disease Nutr. Rev. 2007 65 S140 S146
36. M. H. Pan C. S. Lai S. Dushenkov C. T. Ho Modulation of inflammatory genes by natural dietary bioactive compounds J. Agric. Food Chem. 2009 57 4467 4477
37. M. H. Pan C. S. Lai C. T. Ho Anti-inflammatory activity of natural dietary flavonoids Food Funct. 2010 1 15 31
38. W. Soontornchaiboon S. S. Joo S. M. Kim Anti-inflammatory effects of violaxanthin isolated from microalga Chlorella ellipsoidea in RAW 264.7 macrophages Biol. Pharm. Bull. 2012 35 1137 1144
39. S. J. Lee S. K. Bai K. S. Lee S. Namkoong H. J. Na K. S. Ha J. A. Han S. V. Yim K. Chang Y. G. Kwon S. K. Lee Y. M. Kim Astaxanthin inhibits nitric oxide production and inflammatory gene expression by suppressing I(kappa)B kinase-dependent NF-kappaB activation Mol. Cells 2003 16 97 105
40. S. P. Tabruyn A. W. Griffioen NF-κB: a new player in angiostatic therapy Angiogenesis 2008 11 101 106
41. K. N. Kim S. J. Heo W. J. Yoon S. M. Kang G. Ahn T. H. Yi Y. J. Jeon Fucoxanthin inhibits the inflammatory response by suppressing the activation of NF-kappaB and MAPKs in lipopolysaccharide-induced RAW 264.7 macrophages Eur. J. Pharmacol. 2010 649 369 375
42. A. Salminen M. Lehtonen T. Suuronen K. Kaarniranta J. Huuskonen Terpenoids: natural inhibitors of NF-κB signaling with anti-inflammatory and anticancer potential Cell. Mol. Life Sci. 2008 65 2979 2999
43. K. Izumi-Nagai N. Nagai K. Ohgami S. Satofuka Y. Ozawa K. Tsubota S. Ohno Y. Oike S. Ishida Inhibition of choroidal neovascularization with an anti-inflammatory carotenoid astaxanthin Invest. Ophthalmol. Visual Sci. 2008 49 1679 1685
44. X. R. Xu Z. Y. Zou X. Xiao Y. M. Huang X. Wang X. M. Lin Effects of Lutein Supplement on Serum Inflammatory Cytokines, ApoE and Lipid Profiles in Early Atherosclerosis Population J. Atheroscler. Thromb. 2013 20 170 177
45. J. E. Kim J. O. Leite R. DeOgburn J. A. Smyth R. M. Clark M. L. Fernandez A lutein-enriched diet prevents cholesterol accumulation and decreases oxidized LDL and inflammatory cytokines in the aorta of guinea pigs J. Nutr. 2011 141 1458 1463
46. R. Shanmugasundaram R. K. Selvaraj Lutein supplementation alters inflammatory cytokine production and antioxidant status in F-line turkeys Poult. Sci. 2011 90 971 976
47. R. K. Selvaraj R. Shanmugasundaram K. C. Klasing Effects of dietary lutein and PUFA on PPAR and RXR isomer expression in chickens during an inflammatory response Comp. Biochem. Physiol., Part A: Mol. Integr. Physiol. 2010 157 198 203
48. L. S. Meriwether B. D. Humphrey D. G. Peterson K. C. Klasing E. A. Koutsos Lutein exposure, in ovo or in the diet, reduces parameters of inflammation in the liver and spleen laying-type chicks (Gallus gallus domesticus) J. Anim. Physiol. Anim. Nutr. 2010 94 e115 e122
49. E. H. Lee D. Faulhaber K. M. Hanson W. Ding S. Peters S. Kodali R. D. Granstein Dietary lutein reduces ultraviolet radiation-induced inflammation and immunosuppression J. Invest. Dermatol. 2004 122 510 517
50. M. Sasaki Y. Ozawa T. Kurihara K. Noda Y. Imamura S. Kobayashi S. Ishida K. Tsubota Neuroprotective effect of an antioxidant, lutein, during retinal inflammation Invest. Ophthalmol. Visual Sci. 2009 50 1433 1439
51. S. Y. Li F. K. Fung Z. J. Fu D. Wong H. H. Chan A. C. Lo Anti-inflammatory effects of lutein in retinal ischemic/hypoxic injury: in vivo and in vitro studies Invest. Ophthalmol. Visual Sci. 2012 53 5976 5984
52. S. Gonzalez S. Astner W. An D. Goukassian M. A. Pathak Dietary lutein/zeaxanthin decreases ultraviolet B-induced epidermal hyperproliferation and acute inflammation in hairless mice J. Invest. Dermatol. 2003 121 399 405
53. K. Izumi-Nagai N. Nagai K. Ohgami S. Satofuka Y. Ozawa K. Tsubota K. Umezawa S. Ohno Y. Oike S. Ishida Macular pigment lutein is antiinflammatory in preventing choroidal neovascularization Arterioscler., Thromb., Vasc. Biol. 2007 27 2555 2562
54. X. H. Jin K. Ohgami K. Shiratori Y. Suzuki T. Hirano Y. Koyama K. Yoshida I. Ilieva K. Iseki S. Ohno Inhibitory effects of lutein on endotoxin-induced uveitis in Lewis rats Invest. Ophthalmol. Visual Sci. 2006 47 2562 2568
55. S. K. Bai S. J. Lee H. J. Na K. S. Ha J. A. Han H. Lee Y. G. Kwon C. K. Chung Y. M. Kim Beta-carotene inhibits inflammatory gene expression in lipopolysaccharide-stimulated macrophages by suppressing redox-based NF-kappaB activation Exp. Mol. Med. 2005 37 323 334
56. I. Konishi M. Hosokawa T. Sashima T. Maoka K. Miyashita Suppressive effects of alloxanthin and diatoxanthin from Halocynthia roretzi on LPS-induced expression of pro-inflammatory genes in RAW264.7 cells J. Oleo Sci. 2008 57 181 189
57. S. Boussiba W. Bing J. P. Yuan A. Zarka F. Chen Changes in pigments profile in the green alga Haeamtococcus pluvialis exposed to environmental stresses Biotechnol. Lett. 1999 21 601 604
58. M. Guerin M. E. Huntley M. Olaizola Haematococcus astaxanthin: applications for human health and nutrition Trends Biotechnol. 2003 21 210 216
59. S. Voutilainen T. Nurmi J. Mursu T. H. Rissanen Carotenoids and cardiovascular health Am. J. Clin. Nutr. 2006 83 1265 1271
60. Wikipedia, Cardiovascular disease, http://en.wikipedia.org/wiki/ Cardiovascular-disease, accessed 10 March 2013
61. T. Iwamoto K. Hosoda R. Hirano H. Kurata A. Matsumoto W. Miki M. Kamiyama H. Itakura S. Yamamoto K. Kondo Inhibition of low-density lipoprotein oxidation by astaxanthin J. Atheroscler. Thromb. 2000 7 216 222
62. G. Hussein M. Nakamura Q. Zhao T. Iguchi H. Goto U. Sankawa H. Watanabe Antihypertensive and neuroprotective effects of astaxanthin in experimental animals Biol. Pharm. Bull. 2005 28 47 52
63. Y. Sasaki N. Kobara S. Higashino J. C. Giddings J. Yamamoto Astaxanthin inhibits thrombosis in cerebral vessels of stroke-prone spontaneously hypertensive rats Nutr. Res. 2011 31 784 789
64. J. Monroy-Ruiz M. A. Sevilla R. Carron M. J. Montero Astaxanthin- enriched-diet reduces blood pressure and improves cardiovascular parameters in spontaneously hypertensive rats Pharmacol. Res. 2011 63 44 50
65. R. G. Fassett J. S. Coombes Astaxanthin: a potential therapeutic agent in cardiovascular disease Mar. Drugs 2011 9 447 465
66. H. Yoshida H. Yanai K. Ito Y. Tomono T. Koikeda H. Tsukahara N. Tada Administration of natural astaxanthin increases serum HDL-cholesterol and adiponectin in subjects with mild hyperlipidemia Atherosclerosis 2010 209 520 523
67. H. Miyawaki J. Takahashi H. Tsukahara I. Takehara Effects of astaxanthin on human blood rheology J. Clin. Biochem. Nutr. 2008 43 69 74
68. F. Bray B. Møller Predicting the future burden of cancer Nat. Rev. Cancer 2005 6 63 74
69. V. Zinov'eva A. Spasov Mechanisms of the anticancer effects of plant polyphenols. I. Blockade of initiation of carcinogenesis Biochemistry 2011 5 113 123
70. H. Jyonouchi S. Sun K. Iijima M. D. Gross Antitumor activity of astaxanthin and its mode of action Nutr. Cancer 2000 36 59 65
71. T. Tanaka M. Tanaka T. Kuno Cancer chemoprevention by citrus pulp and juices containing high amounts of beta-cryptoxanthin and hesperidin J. Biomed. Biotechnol. 2012 2012 1 10
72. T. Tanaka T. Kawamori M. Ohnishi H. Makita H. Mori K. Satoh A. Hara Suppression of azoxymethane-induced rat colon carcinogenesis by dietary administration of naturally occurring xanthophylls astaxanthin and canthaxanthin during the postinitiation phase Carcinogenesis 1995 16 2957 2963
73. P. Palozza C. Torelli A. Boninsegna R. Simone A. Catalano M. C. Mele N. Picci Growth-inhibitory effects of the astaxanthin-rich alga Haematococcus pluvialis in human colon cancer cells Cancer Lett. 2009 283 108 117
74. Z. Li Y. M. Wang B. Q. Mo The effects of carotenoids on the proliferation of human breast cancer cell and gene expression of bcl-2 Chin. J. Prev. Med. 2002 36 254 257
75. T. Tanaka Y. Morishita M. Suzui T. Kojima A. Okumura H. Mori Chemoprevention of mouse urinary bladder carcinogenesis by the naturally occurring carotenoid astaxanthin Carcinogenesis 1994 15 15 19
76. M. L. Anderson A preliminary investigation of the enzymatic inhibition of 5α-reductase and growth of prostatic carcinoma cell line LNCap-FGC by natural astaxanthin and saw palmetto lipid extract in vitro J. Herb. Pharmacother. 2005 5 17 26
77. T. Tanaka H. Makita M. Ohnishi H. Mori K. Satoh A. Hara Chemoprevention of rat oral carcinogenesis by naturally occurring xanthophylls, astaxanthin and canthaxanthin Cancer Res. 1995 55 4059 4064
78. F. Daubrawa H. Sies W. Stahl Astaxanthin diminishes gap junctional intercellular communication in primary human fibroblasts J. Nutr. 2005 135 2507 2511
79. J. S. Bertram H. Bortkiewicz Dietary carotenoids inhibit neoplastic transformation and modulate gene expression in mouse and human cells Am. J. Clin. Nutr. 1995 62 1327S 1336S
80. W. Stahl S. Nicolai K. Briviba M. Hanusch G. Broszeit M. Peters H. D. Martin H. Sies Biological activities of natural and synthetic carotenoids: induction of gap junctional communication and singlet oxygen quenching Carcinogenesis 1997 18 89 92
81. L. M. Hix S. F. Lockwood J. S. Bertram Upregulation of connexin 43 protein expression and increased gap junctional communication by water soluble disodium disuccinate astaxanthin derivatives Cancer Lett. 2004 211 25 37
82. J. S. Park J. H. Chyun Y. K. Kim L. L. Line B. P. Chew Astaxanthin decreased oxidative stress and inflammation and enhanced immune response in humans Nutr. Metab. 2010 7 1743 7075
83. H. Kurihara H. Koda S. Asami Y. Kiso T. Tanaka Contribution of the antioxidative property of astaxanthin to its protective effect on the promotion of cancer metastasis in mice treated with restraint stress Life Sci. 2002 70 2509 2520
84. P. N. Prabhu P. Ashokkumar G. Sudhandiran Antioxidative and antiproliferative effects of astaxanthin during the initiation stages of 1,2-dimethyl hydrazine-induced experimental colon carcinogenesis Fundam. Clin. Pharmacol. 2009 23 225 234
85. X. Song M. Wang L. Zhang J. Zhang X. Wang W. Liu X. Gu C. Lv Changes in cell ultrastructure and inhibition of JAK1/STAT3 signaling pathway in CBRH-7919 cells with astaxanthin Toxicol. Mech. Methods 2012 22 679 686
86. J. A. Ansari A. Siraj N. N. Inamdar Pharmacotherapeutic approaches of Parkinson's disease Int. J. Pharmacol. 2010 6 584 590
87. Y. Ikeda S. Tsuji A. Satoh M. Ishikura T. Shirasawa T. Shimizu Protective effects of astaxanthin on 6-hydroxydopamine-induced apoptosis in human neuroblastoma SH-SY5Y cells J. Neurochem. 2008 107 1730 1740
88. X. Liu T. Shibata S. Hisaka T. Osawa Astaxanthin inhibits reactive oxygen species-mediated cellular toxicity in dopaminergic SH-SY5Y cells via mitochondria-targeted protective mechanism Brain Res. 2009 13 18 27
89. D. H. Lee Y. J. Lee K. H. Kwon Neuroprotective Effects of Astaxanthin in Oxygen-Glucose Deprivation in SH-SY5Y Cells and Global Cerebral Ischemia in Rat J. Clin. Biochem. Nutr. 2010 47 121 129
90. K. C. Chan P. J. Pen M. C. Yin Anticoagulatory and antiinflammatory effects of astaxanthin in diabetic rats J. Food Sci. 2012 77 1750 3841
91. Q. Y. Ye B. X. Huang X. D. Zhang Y. G. Zhu X. C. Chen Astaxanthin protects against MPP+-induced oxidative stress in PC12 cells via the HO-1/NOX2 axis BMC Neurosci. 2012 13 156 168
92. J. H. Kim W. Choi J. H. Lee S. J. Jeon Y. H. Choi B. W. Kim H. I. Chang S. W. Nam Astaxanthin inhibits H2O2-mediated apoptotic cell death in mouse neural progenitor cells via modulation of P38 and MEK signaling pathways J. Microbiol. Biotechnol. 2009 19 1355 1363
93. H. Q. Wang X. B. Sun Y. X. Xu H. Zhao Q. Y. Zhu C. Q. Zhu Astaxanthin upregulates heme oxygenase-1 expression through ERK1/2 pathway and its protective effect against beta-amyloid-induced cytotoxicity in SH-SY5Y cells Brain Res. 2010 11 159 167
94. C. H. Chang C. Y. Chen J. Y. Chiou R. Y. Peng C. H. Peng Astaxanthin secured apoptotic death of PC12 cells induced by beta-amyloid peptide 25-35: its molecular action targets J. Med. Food 2010 13 548 556
95. H. Shen C. C. Kuo J. Chou A. Delvolve S. N. Jackson J. Post A. S. Woods B. J. Hoffer Y. Wang B. K. Harvey Astaxanthin reduces ischemic brain injury in adult rats FASEB J. 2009 23 1958 1968
96. Y. P. Lu S. Y. Liu H. Sun X. M. Wu J. J. Li L. Zhu Neuroprotective effect of astaxanthin on H2O2-induced neurotoxicity in vitro and on focal cerebral ischemia in vivo Brain Res. 2010 11 40 48
97. W. Bai X. Wang Z. Wang H. Wang J. Chen The effect of astaxanthin (AST) on Neurotrophin-3 (NT-3) expression in rats after compressive spinal cord injury (SCI)" Afr. J. Pharm. Pharmacol. 2012 6 2559 2564
98. R. Abadie-Guedes R. C. A. Guedes R. S. Bezerra The impairing effect of acute ethanol on spreading depression is antagonized by astaxanthin in rats of 2 young-adult ages Alcohol.: Clin. Exp. Res. 2012 36 1563 1567
99. D. M. Nathan Long-term complications of diabetes mellitus N. Engl. J. Med. 1993 328 1676 1685
100. H. Vlassara M. R. Palace Diabetes and advanced glycation endproducts J. Intern. Med. 2002 251 87 101
101. X. F. Peng J. Y. Ma F. Chen M. F. Wang Naturally occurring inhibitors against the formation of advanced glycation end-products Food Funct. 2011 2 289 301
102. Z. Sun X. F. Peng J. Liu K. W. Fan M. F. Wang F. Chen Inhibitory effects of microalgal extracts on the formation of advanced glycation endproducts (AGEs) Food Chem. 2010 120 261 267
103. Z. Sun J. Liu X. H. Zeng J. Q. Huangfu Y. Jiang M. F. Wang F. Chen Astaxanthin is responsible for antiglycoxidative properties of microalga Chlorella zofingiensis Food Chem. 2011 126 1629 1635
104. Z. Sun J. Liu X. H. Zeng J. Q. Huangfu Y. Jiang M. F. Wang F. Chen Protective actions of microalgae against endogenous and exogenous advanced glycation endproducts (AGEs) in human retinal pigment epithelial cells Food Funct. 2011 2 251 258
105. Y. Naito K. Uchiyama W. Aoi G. Hasegawa N. Nakamura N. Yoshida T. Maoka J. Takahashi T. Yoshikawa Prevention of diabetic nephropathy by treatment with astaxanthin in diabetic db/db mice Biofactors 2004 20 49 59
106. E. Manabe O. Handa Y. Naito K. Mizushima S. Akagiri S. Adachi T. Takagi S. Kokura T. Maoka T. Yoshikawa Astaxanthin protects mesangial cells from hyperglycemia-induced oxidative signaling J. Cell. Biochem. 2008 103 1925 1937
107. D. P. Marin A. P. Bolin R. C. S. Macedo S. C. Sampaio R. Otton ROS production in neutrophils from alloxan-induced diabetic rats treated in vivo with astaxanthin Int. Immunopharmacol. 2011 11 103 109
108. Y. J. Kim Y. A. Kim T. Yokozawa 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
109. K. C. Chan M. C. Mong M. C. Yin Antioxidative and anti-inflammatory neuroprotective effects of astaxanthin and canthaxanthin in nerve growth factor differentiated PC12 cells J. Food Sci. 2009 74 H225 H231
110. Z. W. Zhao W. Cai Y. L. Lin Q. F. Lin Q. Jiang Z. Lin L. L. Chen Ameliorative effect of astaxanthin on endothelial dysfunction in streptozotocin-induced diabetes in male rats Arzneim.-Forsch., Beih. 2011 61 239 246
111. R. Otton D. P. Marin A. P. Bolin R. C. M. Santos T. G. Polotow S. C. Sampaio M. P. de Barros Astaxanthin ameliorates the redox imbalance in lymphocytes of experimental diabetic rats Chem.-Biol. Interact. 2010 186 306 315
112. J. Lee Y. Li C. Li D. Li Natural products and body weight control N. Am. J. Med. Sci. 2011 3 13 19
113. T. Wu Z. P. Yu Q. Tang H. Z. Song Z. C. Gao W. Chen X. D. Zheng Honeysuckle anthocyanin supplementation prevents diet-induced obesity in C57BL/6 mice Food Funct. 2013 4 1654 1661
114. M. Ikeuchi T. Koyama J. Takahashi K. Yazawa Effects of astaxanthin in obese mice fed a high-fat diet Biosci., Biotechnol., Biochem. 2007 71 893 899
115. M. Ikeuchi T. Koyama J. Takahashi K. Yazawa Effects of astaxanthin supplementation on exercise-induced fatigue in mice Biol. Pharm. Bull. 2006 29 2106 2110
116. H. D. Choi J. H. Kim M. J. Chang Y. Kyu-Youn W. G. Shin Effects of astaxanthin on oxidative stress in overweight and obese adults Phytother. Res. 2011 25 1813 1818
117. M. F. McCarty Full-spectrum antioxidant therapy featuring astaxanthin coupled with lipoprivic strategies and salsalate for management of non-alcoholic fatty liver disease Med. Hypotheses 2011 77 550 556
118. E. Arunkumar S. Bhuvaneswari C. V. Anuradha An intervention study in obese mice with astaxanthin, a marine carotenoid-effects on insulin signaling and pro-inflammatory cytokines Food Funct. 2012 3 120 126
119. G. Hussein T. Nakagawa H. Goto Y. Shimada K. Matsumoto U. Sankawa H. Watanabe Astaxanthin ameliorates features of metabolic syndrome in SHR/NDmcr-cp Life Sci. 2007 80 522 529
120. S. Bhuvaneswari C. V. Anuradha Astaxanthin prevents loss of insulin signaling and improves glucose metabolism in liver of insulin resistant mice Can. J. Physiol. Pharmacol. 2012 90 1544 1552
121. M. Ishiki Y. Nishida H. Ishibashi T. Wada S. Fujisaka A. Takikawa M. Urakaze T. Sasaoka I. Usui K. Tobe Impact of divergent effects of astaxanthin on Insulin Signaling in L6 cells Endocrinology 2013 154 2600 2612
122. M. Inoue H. Tanabe A. Matsumoto M. Takagi K. Umegaki S. Amagaya J. Takahashi Astaxanthin functions differently as a selective peroxisome proliferator-activated receptor γ modulator in adipocytes and macrophages Biochem. Pharmacol. 2012 84 692 700
123. C. C. Hu J. T. Lin F. J. Lu F. P. Chou D. J. Yang Determination of carotenoids in Dunaliella salina cultivated in Taiwan and antioxidant capacity of the algal carotenoid extract Food Chem. 2008 109 439 446
124. X. M. Shi X. W. Zhang F. Chen Heterotrophic production of biomass and lutein by Chlorella protothecoides on various nitrogen sources Enzyme Microb. Technol. 2000 27 312 318
125. X. M. Shi Y. Jiang F. Chen High-Yield Production of Lutein by the Green Microalga Chlorella protothecoides in Heterotrophic Fed-Batch Culture Biotechnol. Prog. 2002 18 723 727
126. J. F. Sánchez J. M. Fernández F. G. Acién A. Rueda J. Pérez-Parra E. Molina Influence of culture conditions on the productivity and lutein content of the new strain Scenedesmus almeriensis Process Biochem. 2008 43 398 405
127. G. Graziani S. Schiavo M. A. Nicolai S. Buono V. Fogliano G. Pinto A. Pollio Microalgae as human food: chemical and nutritional characteristics of the thermo-acidophilic microalga Galdieria sulphuraria Food Funct. 2013 4 144 152
128. M. Orosa J. F. Valero C. Herrero J. Abalde Comparison of the accumulation of astaxanthin in Haematococcus pluvialis and other green microalgae under N-starvation and high light conditions Biotechnol. Lett. 2001 23 1079 1085
129. A. Domínguez-Bocanegra I. Guerrero Legarreta F. Martinez Jeronimo A. Tomasini Campocosio Influence of environmental and nutritional factors in the production of astaxanthin from Haematococcus pluvialis Bioresour. Technol. 2004 92 209 214
130. T. Chen Y. Wang Optimized astaxanthin production in Chlorella zofingiensis under dark condition by response surface methodology Food Sci. Biotechnol. 2013 22 1343 1350
131. N. Sun Y. Wang Y. T. Li J. C. Huang F. Chen Sugar-based growth, astaxanthin accumulation and carotenogenic transcription of heterotrophic Chlorella zofingiensis (Chlorophyta) Process Biochem. 2008 43 1288 1292
132. Y. Wang Z. Liu S. Qin Effects of iron on fatty acid and astaxanthin accumulation in mixotrophic Chromochloris zofingiensis Biotechnol. Lett. 2013 35 351 357
133. M. Obulesu M. R. Dowlathabad P. V. Bramhachari Carotenoids and Alzheimer's disease: an insight into therapeutic role of retinoids in animal models Neurochem. Int. 2011 59 535 541
134. M. Etminan S. S. Gill A. Samii Intake of vitamin E, vitamin C, and carotenoids and the risk of Parkinson's disease: a meta-analysis Lancet Neurol. 2005 4 362 365
135. M. Agarwal R. P. Parameswari H. R. Vasanthi D. K. Das Dynamic Action of Carotenoids in Cardioprotection and Maintenance of Cardiac Health Molecules 2012 17 4755 4769
136. J. H. Dwyer M. Navab K. M. Dwyer K. Hassan P. Sun A. Shircore S. Hama-Levy G. Hough X. P. Wang T. Drake C. N. B. Merz A. M. Fogelman Oxygenated carotenoid lutein and progression of early atherosclerosis: the Los Angeles atherosclerosis study Circulation 2001 103 2922 2927
137. S. K. Ryu T. J. King K. Fujioka J. Pattison F. J. Pashkow S. Tsimikas 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
138. Y. Ozawa M. Sasaki N. Takahashi M. Kamoshita S. Miyake K. Tsubota Neuroprotective Effects of Lutein in the Retina Curr. Pharm. Des. 2012 18 51 56
139. R. A. Kowluru B. Menon D. L. Gierhart Beneficial effect of zeaxanthin on retinal metabolic abnormalities in diabetic rats Invest. Ophthalmol. Visual Sci. 2008 49 1645 1651
140. L. M. Renzi E. J. Johnson Lutein and age-related ocular disorders in the older adult: a review J. Nutr. Elder. 2007 26 139 157
141. M. Yamaguchi Role of carotenoid beta-cryptoxanthin in bone homeostasis J. Biomed. Sci. 2012 19 36
142. F. H. Comhaire Y. El Garem A. Mahmoud F. Eertmans F. Schoonjans Combined conventional/antioxidant "Astaxanthin" treatment for male infertility: a double blind, randomized trial Asian J. Androl. 2005 7 257 262
143. S. H. Kim D. I. Jean Y. P. Lim C. Lee G. An Weight gain limitation and liver protection by long-term feeding of astaxanthin in murines J. Korean Soc. Appl. Biol. Chem. 2009 52 180 185
144. W. F. Seifert A. Bosma H. F. J. Hendriks R. E. W. van Leeuwen G. C. F. van Thiel-de Ruiter I. Seifert-Bock D. L. Knook A. Brouwer Beta-carotene (provitamin A) decreases the severity of CCl4-induced hepatic inflammation and fibrosis in rats Liver 1995 15 1 8
145. A. Lavy Y. Naveh R. Coleman S. Mokady M. J. Werman Dietary Dunaliella bardawil, a beta-carotene-rich alga, protects against acetic acid-induced small bowel inflammation in rats Inflammatory Bowel Dis. 2003 9 372 379
146. G. Kaliappan P. Nagarajan R. Moorthy S. Kalai Gana Selvi T. Avinash Raj J. Mahesh Kumar Ang II induce kidney damage by recruiting inflammatory cells and up regulates PPAR gamma and Renin 1 gene: effect of beta carotene on chronic renal damage J. Thromb. Thrombolysis 2013 36 277 285
147. J. Helmersson J. Ärnlöv A. Larsson S. Basu Low dietary intake of beta-carotene, alpha-tocopherol and ascorbic acid is associated with increased inflammatory and oxidative stress status in a Swedish cohort Br. J. Nutr. 2009 101 1775 1782
148. Q. Bian S. Gao J. Zhou J. Qin A. Taylor E. J. Johnson G. Tang J. R. Sparrow D. Gierhart F. Shang Lutein and zeaxanthin supplementation reduces photooxidative damage and modulates the expression of inflammation-related genes in retinal pigment epithelial cells Free Radical Biol. Med. 2012 53 1298 1307
149. Y. Yasui M. Hosokawa N. Mikami K. Miyashita T. Tanaka Dietary astaxanthin inhibits colitis and colitis-associated colon carcinogenesis in mice via modulation of the inflammatory cytokines Chem.-Biol. Interact. 2011 193 79 87
150. R. Nakao O. L. Nelson J. S. Park B. D. Mathison P. A. Thompson B. P. Chew Effect of astaxanthin supplementation on inflammation and cardiac function in BALB/c mice Anticancer Res. 2010 30 2721 2725
151. K. Ohgami K. Shiratori S. Kotake T. Nishida N. Mizuki K. Yazawa S. Ohno Effects of astaxanthin on lipopolysaccharide-induced inflammation in vitro and in vivo Invest. Ophthalmol. Visual Sci. 2003 44 2694 2701
152. L. M. Hix D. A. Frey M. D. McLaws M. Østerlie S. F. Lockwood J. S. Bertram Inhibition of chemically-induced neoplastic transformation by a novel tetrasodium diphosphate astaxanthin derivative Carcinogenesis 2005 26 1634 1641