Potential health-promoting effects of astaxanthin: a high-value carotenoid mostly from microalgae.

The ketocarotenoid astaxanthin can be found in the microalgae Haematococcus pluvialis, Chlorella zofingiensis, and Chlorococcum sp., and the red yeast Phaffia rhodozyma. The microalga H. pluvialis has the highest capacity to accumulate astaxanthin up to 4-5% of cell dry weight. Astaxanthin has been attributed with extraordinary potential for protecting the organism against a wide range of diseases, and has considerable potential and promising applications in human health. Numerous studies have shown that astaxanthin has potential health-promoting effects in the prevention and treatment of various diseases, such as cancers, chronic inflammatory diseases, metabolic syndrome, diabetes, diabetic nephropathy, cardiovascular diseases, gastrointestinal diseases, liver diseases, neurodegenerative diseases, eye diseases, skin diseases, exercise-induced fatigue, male infertility, and HgCl₂-induced acute renal failure. In this article, the currently available scientific literature regarding the most significant activities of astaxanthin is reviewed.

[1]  D. Bagchi,et al.  Astaxanthin lowers blood pressure and lessens the activity of the renin-angiotensin system in Zucker Fatty Rats , 2009 .

[2]  R. Otton,et al.  In vivo astaxanthin treatment partially prevents antioxidant alterations in dental pulp from alloxan-induced diabetic rats. , 2010, International endodontic journal.

[3]  Gokare A. Ravishankar,et al.  Ulcer preventive and antioxidative properties of astaxanthin from Haematococcus pluvialis. , 2008, European journal of pharmacology.

[4]  岩本 珠美.  Inhibition of low-density lipoprotein oxidation by astaxanthin , 2002 .

[5]  Xuebo Liu,et al.  Astaxanthin inhibits reactive oxygen species-mediated cellular toxicity in dopaminergic SH-SY5Y cells via mitochondria-targeted protective mechanism , 2009, Brain Research.

[6]  Y. Naito,et al.  Astaxanthin protects β-cells against glucose toxicity in diabetic db/db mice , 2002 .

[7]  Kinzo Matsumoto,et al.  Astaxanthin, a carotenoid with potential in human health and nutrition. , 2006, Journal of natural products.

[8]  T. Emanuelli,et al.  Effect of astaxanthin on kidney function impairment and oxidative stress induced by mercuric chloride in rats. , 2008, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[9]  T. Toda,et al.  Antiadult T‐cell leukemia effects of brown algae fucoxanthin and its deacetylated product, fucoxanthinol , 2008, International journal of cancer.

[10]  D. Marin,et al.  Astaxanthin prevents in vitro auto-oxidative injury in human lymphocytes , 2010, Cell Biology and Toxicology.

[11]  Hui Shen,et al.  Astaxanthin reduces ischemic brain injury in adult rats , 2009, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[12]  G. Imokawa,et al.  Astaxanthin attenuates the UVA-induced up-regulation of matrix-metalloproteinase-1 and skin fibroblast elastase in human dermal fibroblasts. , 2010, Journal of dermatological science.

[13]  R. Edge,et al.  Reduction of oxidized guanosine by dietary carotenoids: a pulse radiolysis study. , 2010, Archives of biochemistry and biophysics.

[14]  M. Murakoshi,et al.  Carotenoids in Cancer Chemoprevention , 2004, Cancer and Metastasis Reviews.

[15]  B. Mathison,et al.  Effect of dietary astaxanthin at different stages of mammary tumor initiation in BALB/c mice. , 2010, Anticancer research.

[16]  K. Iijima,et al.  Intervention of astaxanthin against cyclophosphamide ‐ induced oxidative stress and DNA damage : a study in mice , 2010 .

[17]  T. Nadamoto,et al.  Effects of astaxanthin and vitamin C on the prevention of gastric ulcerations in stressed rats. , 2005, Journal of nutritional science and vitaminology.

[18]  T. Maoka,et al.  Astaxanthin protects mesangial cells from hyperglycemia‐induced oxidative signaling , 2008, Journal of cellular biochemistry.

[19]  F Berrino,et al.  Plasma and dietary carotenoid, retinol and tocopherol levels and the risk of gastric adenocarcinomas in the European prospective investigation into cancer and nutrition , 2006, British Journal of Cancer.

[20]  B. Lucchesi,et al.  Disodium Disuccinate Astaxanthin (Cardax) Attenuates Complement Activation and Reduces Myocardial Injury following Ischemia/Reperfusion , 2005, Journal of Pharmacology and Experimental Therapeutics.

[21]  F. Pashkow,et al.  Astaxanthin: a novel potential treatment for oxidative stress and inflammation in cardiovascular disease. , 2008, The American journal of cardiology.

[22]  J. Bertram.  Induction of connexin 43 by carotenoids: functional consequences. , 2004, Archives of biochemistry and biophysics.

[23]  Takaharu Tanaka,et al.  Contribution of the antioxidative property of astaxanthin to its protective effect on the promotion of cancer metastasis in mice treated with restraint stress. , 2002, Life sciences.

[24]  Xin Liu,et al.  Carotenoid composition in the green microalga Chlorococcum , 2002 .

[25]  M. Yamaguchi,et al.  Sports Performance Benefits from Taking Natural Astaxaxxthin * Characterized by Visual Acuity and Muscular Fatigue Improvement in Humans , 2004 .

[26]  R. Walsh,et al.  Anti‐ and Prooxidant Properties of Carotenoids , 1999 .

[27]  K. Masuda,et al.  Effect of Astaxanthin on Accommodation and Asthenopia , 2011 .

[28]  R. Otton,et al.  Astaxanthin restores the enzymatic antioxidant profile in salivary gland of alloxan-induced diabetic rats. , 2010, Archives of oral biology.

[29]  U. Lemmer,et al.  Visualization of astaxanthin localization in HT29 human colon adenocarcinoma cells by combined confocal resonance Raman and fluorescence microspectroscopy. , 2006, Molecular nutrition & food research.

[30]  R. Willén,et al.  Treatment of H. pylori infected mice with antioxidant astaxanthin reduces gastric inflammation, bacterial load and modulates cytokine release by splenocytes. , 2000, Immunology letters.

[31]  T. Hibi,et al.  An antioxidant resveratrol significantly enhanced replication of hepatitis C virus. , 2010, World journal of gastroenterology.

[32]  F. Chen,et al.  Isomerization of trans-astaxanthin to cis-isomers in organic solvents. , 1999, Journal of agricultural and food chemistry.

[33]  K. Ohgami,et al.  Effects of astaxanthin on lipopolysaccharide-induced inflammation in vitro and in vivo. , 2003, Investigative ophthalmology & visual science.

[34]  Y. Akyön.  Effect of antioxidants on the immune response of Helicobacter pylori. , 2002, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[35]  G. An,et al.  Astaxanthin from Microbial Sources , 1991 .

[36]  Y. Miura,et al.  Inhibitory effects of carotenoids on the invasion of rat ascites hepatoma cells in culture. , 2000, Cancer letters.

[37]  K. Tsubota,et al.  Inhibition of choroidal neovascularization with an anti-inflammatory carotenoid astaxanthin. , 2008, Investigative ophthalmology & visual science.

[38]  Cheng-Wei Lu,et al.  Astaxanthin inhibits glutamate release in rat cerebral cortex nerve terminals via suppression of voltage-dependent Ca(2+) entry and mitogen-activated protein kinase signaling pathway. , 2010, Journal of agricultural and food chemistry.

[39]  Kinzo Matsumoto,et al.  Astaxanthin ameliorates features of metabolic syndrome in SHR/NDmcr-cp. , 2007, Life sciences.

[40]  M. Yin,et al.  Antioxidative and anti-inflammatory neuroprotective effects of astaxanthin and canthaxanthin in nerve growth factor differentiated PC12 cells. , 2009, Journal of food science.

[41]  S. Kim,et al.  Effect of astaxanthin on the hepatotoxicity, lipid peroxidation and antioxidative enzymes in the liver of CCl4-treated rats. , 2001, Methods and findings in experimental and clinical pharmacology.

[42]  A. Asai,et al.  Esterification of xanthophylls by human intestinal Caco-2 cells. , 2009, Archives of biochemistry and biophysics.

[43]  Gokare A. Ravishankar,et al.  Characterization of microalgal carotenoids by mass spectrometry and their bioavailability and antioxidant properties elucidated in rat model. , 2010, Journal of agricultural and food chemistry.

[44]  E. Camera,et al.  Astaxanthin, canthaxanthin and β‐carotene differently affect UVA‐induced oxidative damage and expression of oxidative stress‐responsive enzymes , 2009, Experimental dermatology.

[45]  Xuebo Liu,et al.  Cis astaxanthin and especially 9-cis astaxanthin exhibits a higher antioxidant activity in vitro compared to the all-trans isomer. , 2007, Biochemical and biophysical research communications.

[46]  B. Mathison,et al.  Effect of astaxanthin supplementation on inflammation and cardiac function in BALB/c mice. , 2010, Anticancer research.

[47]  R. Willén,et al.  Astaxanthin-Rich Algal Meal and Vitamin C InhibitHelicobacter pylori Infection in BALB/cA Mice , 2000, Antimicrobial Agents and Chemotherapy.

[48]  F. Mahmoud,et al.  In vitro effects of astaxanthin combined with ginkgolide B on T lymphocyte activation in peripheral blood mononuclear cells from asthmatic subjects. , 2004, Journal of pharmacological sciences.

[49]  Yeguang Li,et al.  Characterization of astaxanthin esters in Haematococcus pluvialis by liquid chromatography-atmospheric pressure chemical ionization mass spectrometry. , 2006, Analytical biochemistry.

[50]  P. Palozza,et al.  The protective role of carotenoids against 7-keto-cholesterol formation in solution , 2008, Molecular and Cellular Biochemistry.

[51]  W. Stahl,et al.  Astaxanthin diminishes gap junctional intercellular communication in primary human fibroblasts. , 2005, The Journal of nutrition.

[52]  H. Chang,et al.  Suppressive Effect of Astaxanthin Isolated from the Xanthophyllomyces dendrorhous Mutant on Ethanol-Induced Gastric Mucosal Injury in Rats , 2005, Bioscience, biotechnology, and biochemistry.

[53]  Y. Naito,et al.  Astaxanthin improves muscle lipid metabolism in exercise via inhibitory effect of oxidative CPT I modification. , 2008, Biochemical and biophysical research communications.

[54]  Y. Naguib.  Antioxidant activities of astaxanthin and related carotenoids. , 2000, Journal of agricultural and food chemistry.

[55]  Á. Tósaki,et al.  Summative interaction between astaxanthin, Ginkgo biloba extract (EGb761) and vitamin C in Suppression of respiratory inflammation: a comparison with ibuprofen , 2011, Phytotherapy research : PTR.

[56]  M. Aslan,et al.  Suppressive effect of astaxanthin on retinal injury induced by elevated intraocular pressure. , 2010, Regulatory toxicology and pharmacology : RTP.

[57]  C. Peng,et al.  Astaxanthine secured apoptotic death of PC12 cells induced by beta-amyloid peptide 25-35: its molecular action targets. , 2010, Journal of medicinal food.

[58]  S. Boussiba.  Carotenogenesis in the green alga Haematococcus pluvialis: Cellular physiology and stress response , 2000 .

[59]  Feng Chen,et al.  Changes in pigments profile in the green alga Haeamtococcus pluvialis exposed to environmental stresses , 1999, Biotechnology Letters.

[60]  N. O'Brien,et al.  Modulatory effects of an algal extract containing astaxanthin on UVA-irradiated cells in culture. , 2002, Journal of dermatological science.

[61]  R T Lorenz,et al.  Commercial potential for Haematococcus microalgae as a natural source of astaxanthin. , 2000, Trends in biotechnology.

[62]  A. Zarka,et al.  ACCUMULATION OF OLEIC ACID IN HAEMATOCOCCUS PLUVIALIS (CHLOROPHYCEAE) UNDER NITROGEN STARVATION OR HIGH LIGHT IS CORRELATED WITH THAT OF ASTAXANTHIN ESTERS1 , 2002 .

[63]  G. Block,et al.  Antioxidant intake is associated with semen quality in healthy men. , 2005, Human reproduction.

[64]  Dennis Lara Hernández,et al.  of for , 2007 .

[65]  T. Koyama,et al.  Effects of Astaxanthin in Obese Mice Fed a High-Fat Diet , 2007, Bioscience, biotechnology, and biochemistry.

[66]  N. Tada,et al.  Administration of natural astaxanthin increases serum HDL-cholesterol and adiponectin in subjects with mild hyperlipidemia. , 2010, Atherosclerosis.

[67]  K. Kondo,et al.  Astaxanthin suppresses scavenger receptor expression and matrix metalloproteinase activity in macrophages , 2010, European journal of nutrition.

[68]  D. Tripathi,et al.  Astaxanthin intervention ameliorates cyclophosphamide-induced oxidative stress, DNA damage and early hepatocarcinogenesis in rat: role of Nrf2, p53, p38 and phase-II enzymes. , 2010, Mutation research.

[69]  F. Goycoolea,et al.  Astaxanthin: A Review of its Chemistry and Applications , 2006, Critical reviews in food science and nutrition.

[70]  R. Jacob,et al.  Biologic activity of carotenoids related to distinct membrane physicochemical interactions. , 2008, American Journal of Cardiology.

[71]  T. Emanuelli,et al.  Astaxanthin Reduces Oxidative Stress, but not Aortic Damage in Atherosclerotic Rabbits , 2009, Journal of cardiovascular pharmacology and therapeutics.

[72]  Feng Chen,et al.  Kinetics for the reversible isomerization reaction of trans-astaxanthin , 2001 .

[73]  S. Kase,et al.  Suppressive effects of astaxanthin against rat endotoxin-induced uveitis by inhibiting the NF-kappaB signaling pathway. , 2006, Experimental eye research.

[74]  G. Sudhandiran,et al.  Antioxidative and antiproliferative effects of astaxanthin during the initiation stages of 1,2‐dimethyl hydrazine‐induced experimental colon carcinogenesis , 2009, Fundamental & clinical pharmacology.

[75]  H. Gottlieb,et al.  Accumulation of Secondary Carotenoids in Chlorella zofingiensis , 1994 .

[76]  Y. Ikeda,et al.  Protective effects of astaxanthin on 6‐hydroxydopamine‐induced apoptosis in human neuroblastoma SH‐SY5Y cells , 2008, Journal of neurochemistry.

[77]  G. Song,et al.  Protective effect of astaxanthin on naproxen-induced gastric antral ulceration in rats. , 2005, European journal of pharmacology.

[78]  Juan Peng,et al.  Comparative analysis of astaxanthin and its esters in the mutant E1 of Haematococcus pluvialis and other green algae by HPLC with a C30 column , 2008, Science in China Series C: Life Sciences.

[79]  Feng Chen,et al.  Chromatographic separation and purification of trans-astaxanthin from the extracts of Haematococcus pluvialis , 1998 .

[80]  R. Otton,et al.  Astaxanthin ameliorates the redox imbalance in lymphocytes of experimental diabetic rats. , 2010, Chemico-biological interactions.

[81]  Hiroshi Watanabe,et al.  Antihypertensive and neuroprotective effects of astaxanthin in experimental animals. , 2005, Biological & pharmaceutical bulletin.

[82]  Y. Naito,et al.  Microarray profiling of gene expression patterns in glomerular cells of astaxanthin-treated diabetic mice: a nutrigenomic approach. , 2006, International journal of molecular medicine.

[83]  R. Guedes,et al.  Dose-dependent effects of astaxanthin on cortical spreading depression in chronically ethanol-treated adult rats. , 2008, Alcoholism, clinical and experimental research.

[84]  M. Wójcik,et al.  Effect of carotenoids on in vitro proliferation and differentiation of oval cells during neoplastic and non-neoplastic liver injuries in rats. , 2008, Journal of physiology and pharmacology : an official journal of the Polish Physiological Society.

[85]  Yung-Hyun Choi,et al.  Astaxanthin inhibits H2O2-mediated apoptotic cell death in mouse neural progenitor cells via modulation of P38 and MEK signaling pathways. , 2009, Journal of microbiology and biotechnology.

[86]  I. Nishigaki,et al.  Cytoprotective role of astaxanthin against glycated protein/iron chelate‐induced toxicity in human umbilical vein endothelial cells , 2010, Phytotherapy research : PTR.

[87]  K. Takahashi,et al.  Uptake and distribution of astaxanthin in several tissues and plasma lipoproteins in male broiler chickens fed a yeast (Phaffia rhodozyma) with a high concentration of astaxanthin , 2004, British poultry science.

[88]  K. Kitahama,et al.  Efficient radical trapping at the surface and inside the phospholipid membrane is responsible for highly potent antiperoxidative activity of the carotenoid astaxanthin. , 2001, Biochimica et biophysica acta.

[89]  J. Liao,et al.  Astaxanthin protects against oxidative stress and calcium-induced porcine lens protein degradation. , 2006, Journal of agricultural and food chemistry.

[90]  Feng Chen,et al.  Purification of trans-astaxanthin from a high-yielding astaxanthin ester-producing strain of the microalga Haematococcus pluvialis , 2000 .

[91]  A. Olsson,et al.  Alpha-tocopherol and astaxanthin decrease macrophage infiltration, apoptosis and vulnerability in atheroma of hyperlipidaemic rabbits. , 2004, Journal of molecular and cellular cardiology.

[92]  F. Comhaire,et al.  Combined conventional/antioxidant "Astaxanthin" treatment for male infertility: a double blind, randomized trial. , 2005, Asian journal of andrology.

[93]  T. Bohn.  Bioavailability of Non-Provitamin A Carotenoids , 2008 .

[94]  J. Bertram,et al.  Cancer prevention by retinoids and carotenoids: independent action on a common target. , 2005, Biochimica et biophysica acta.

[95]  C. Anuradha,et al.  Astaxanthin restricts weight gain, promotes insulin sensitivity and curtails fatty liver disease in mice fed a obesity-promoting diet , 2010 .

[96]  T. Wong,et al.  A comparison of the anticancer activities of dietary beta-carotene, canthaxanthin and astaxanthin in mice in vivo. , 1999, Anticancer research.

[97]  D. Choi,et al.  Effects of astaxanthin on the production of NO and the expression of COX-2 and iNOS in LPS-stimulated BV2 microglial cells. , 2008, Journal of microbiology and biotechnology.

[98]  D. Marin,et al.  Astaxanthin addition improves human neutrophils function: in vitro study , 2010, European journal of nutrition.

[99]  M. Suzui,et al.  Chemoprevention of mouse urinary bladder carcinogenesis by the naturally occurring carotenoid astaxanthin. , 1994, Carcinogenesis.

[100]  Kinzo Matsumoto,et al.  Antihypertensive potential and mechanism of action of astaxanthin: III. Antioxidant and histopathological effects in spontaneously hypertensive rats. , 2006, Biological & pharmaceutical bulletin.

[101]  Y. K. Lee,et al.  Effect of total secondary carotenoids extracts from Chlorococcum sp on Helicobacter pylori-infected BALB/c mice. , 2003, International immunopharmacology.

[102]  Kinzo Matsumoto,et al.  Antihypertensive potential and mechanism of action of astaxanthin: II. Vascular reactivity and hemorheology in spontaneously hypertensive rats. , 2005, Biological & pharmaceutical bulletin.

[103]  T. Maoka,et al.  Prevention of diabetic nephropathy by treatment with astaxanthin in diabetic db/db mice , 2004, BioFactors.

[104]  T. Maoka,et al.  Astaxanthin limits exercise-induced skeletal and cardiac muscle damage in mice. , 2003, Antioxidants & redox signaling.

[105]  R. Bergès,et al.  Dietary carotenoids inhibit aflatoxin B1-induced liver preneoplastic foci and DNA damage in the rat: role of the modulation of aflatoxin B1 metabolism. , 1998, Carcinogenesis.

[106]  T. Yokozawa,et al.  Protection against oxidative stress, inflammation, and apoptosis of high-glucose-exposed proximal tubular epithelial cells by astaxanthin. , 2009, Journal of agricultural and food chemistry.

[107]  D. Tripathi,et al.  Astaxanthin inhibits cytotoxic and genotoxic effects of cyclophosphamide in mice germ cells. , 2008, Toxicology.

[108]  P. Palozza,et al.  Growth-inhibitory effects of the astaxanthin-rich alga Haematococcus pluvialis in human colon cancer cells. , 2009, Cancer letters.

[109]  K. Ha,et al.  Astaxanthin inhibits nitric oxide production and inflammatory gene expression by suppressing I ( kappa ) B kinase-dependent NF-kappaB activation , 2010 .

[110]  L. Kupčinskas,et al.  Efficacy of the natural antioxidant astaxanthin in the treatment of functional dyspepsia in patients with or without Helicobacter pylori infection: A prospective, randomized, double blind, and placebo-controlled study. , 2008, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[111]  N. Demir,et al.  Effect of astaxanthin on hepatocellular injury following ischemia/reperfusion. , 2010, Toxicology.

[112]  B. Chew,et al.  Carotenoid action on the immune response. , 2004, The Journal of nutrition.

[113]  R. Jacob,et al.  Differential effects of carotenoids on lipid peroxidation due to membrane interactions: X-ray diffraction analysis. , 2007, Biochimica et biophysica acta.

[114]  Yung-Hyun Choi,et al.  Astaxanthin improves the proliferative capacity as well as the osteogenic and adipogenic differentiation potential in neural stem cells. , 2010, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[115]  T. Koyama,et al.  Effects of astaxanthin supplementation on exercise-induced fatigue in mice. , 2006, Biological & pharmaceutical bulletin.

[116]  B. Chew,et al.  Astaxanthin decreased oxidative stress and inflammation and enhanced immune response in humans , 2010, Nutrition & metabolism.

[117]  Y. Hirose,et al.  Chemoprevention by naturally occurring and synthetic agents in oral, liver, and large bowel carcinogenesis , 1997, Journal of cellular biochemistry. Supplement.

[118]  Kumiko,et al.  Chemoprevention of rat oral carcinogenesis by naturally occurring xanthophylls, astaxanthin and canthaxanthin. , 1995, Cancer research.

[119]  Miyako Tanabe,et al.  Effect of astaxanthin in combination with alpha-tocopherol or ascorbic acid against oxidative damage in diabetic ODS rats. , 2008, Journal of nutritional science and vitaminology.

[120]  Nagaki Yasunori,et al.  The Effect of Astaxanthin on Retinal Capillary Blood Flow in Normal Volunteers , 2005 .

[121]  K. Matsubara,et al.  Inhibitory Effect of Carotenoids on the Degranulation of Mast Cells via Suppression of Antigen-induced Aggregation of High Affinity IgE Receptors* , 2009, The Journal of Biological Chemistry.