The antioxidant, immunomodulatory, and anti-inflammatory activities of Spirulina: an overview

Abstract

Spirulina is a species of filamentous cyanobacteria that has long been used as a food supplement. In particular, Spirulina platensis and Spirulina maxima are the most important. Thanks to a high protein and vitamin content, Spirulina is used as a nutraceutical food supplement, although its other potential health benefits have attracted much attention. Oxidative stress and dysfunctional immunity cause many diseases in humans, including atherosclerosis, cardiac hypertrophy, heart failure, and hypertension. Thus, the antioxidant, immunomodulatory, and anti-inflammatory activities of these microalgae may play an important role in human health. Here, we discuss the antioxidant, immunomodulatory, and anti-inflammatory activities of Spirulina in both animals and humans, along with the underlying mechanisms. In addition, its commercial and regulatory status in different countries is discussed as well. Spirulina activates cellular antioxidant enzymes, inhibits lipid peroxidation and DNA damage, scavenges free radicals, and increases the activity of superoxide dismutase and catalase. Notably, there appears to be a threshold level above which Spirulina will taper off the antioxidant activity. Clinical trials show that Spirulina prevents skeletal muscle damage under conditions of exercise-induced oxidative stress and can stimulate the production of antibodies and up- or downregulate the expression of cytokine-encoding genes to induce immunomodulatory and anti-inflammatory responses. The molecular mechanism(s) by which Spirulina induces these activities is unclear, but phycocyanin and β-carotene are important molecules. Moreover, Spirulina effectively regulates the ERK1/2, JNK, p38, and IκB pathways. This review provides new insight into the potential therapeutic applications of Spirulina and may provide new ideas for future studies.

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Abbreviations

FDA:

Food and drug administration

GRAS:

Generally recognized as safe

COPD:

Chronic obstructive pulmonary disease

IL:

Interleukin

TNF:

Tumor necrosis factor

MAPK:

Mitogen-activated protein kinase

ROS:

Reactive oxygen species

MDA:

Malondialdehyde

SOD:

Superoxide dismutase

CAT:

Catalase

GPx:

Glutathione peroxidase

GR:

Glutathione reductase

PX:

Peroxidase

APx:

Ascorbate peroxidase

GSH:

Glutathione

GST:

Glutathione S-transferase

DPPH:

2,2-Diphenyl-1-picrylhydrazyl

HSC:

Hepatic stellate cell

HCD:

High-cholesterol diet

PHGPx:

Phospholipid hydroperoxide glutathione peroxidase

6-OHDA:

6-Hydroxydopamine

DLM:

Deltamethrin

NASH:

Nonalcoholic steatohepatitis

ALT:

Alanine aminotransferase

OSF:

Oral submucous fibrosis

COPD:

Chronic obstructive pulmonary disease

AST:

Aspartate transaminase

NO:

Nitric oxide

Se:

Selenium

Te:

Tellurium

IFN:

Interferon

PHA:

Phytohemagglutinin

LPS:

Lipopolysaccharide

iNOS:

Inducible nitric oxide synthase

COX-2:

Cyclooxygenase-2

eNOS:

Endothelial nitric oxide synthase

MPO:

Myeloperoxidase

NASH:

Nonalcoholic steatohepatitis

PD:

Parkinson’s disease

AAV9:

Adeno-associated virus vector

NMDA:

N-methyl d-aspartate receptor

OSF:

Oral submucous fibrosis

References

  1. Abd El-Baky HH, El Baz FK, El-Baroty GS (2009) Enhancement of antioxidant production in Spirulina platensis under oxidative stress. Acta Physiol Plant 31:623–631

    CAS  Article  Google Scholar 

  2. Abdel-Daim MM, Abuzead SM, Halawa SM (2013) Protective role of Spirulina platensis against acute deltamethrin-induced toxicity in rats. PLoS ONE 8(9):e72991

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  3. Abdel-Daim MM, Farouk SM, Madkour FF et al (2015) Anti-inflammatory and immunomodulatory effects of Spirulina platensis in comparison to Dunaliella salina in acetic acid-induced rat experimental colitis. Immunopharmacol Immunotoxicol 37(2):126–139

    CAS  PubMed  Article  Google Scholar 

  4. Abdelkhalek NK, Ghazy EW, Abdel-Daim MM (2015) Pharmacodynamic interaction of Spirulina platensis and deltamethrin in freshwater fish Nile tilapia, Oreochromis niloticus: impact on lipid peroxidation and oxidative stress. Environ Sci Pollut Res Int 22(4):3023–3031

    CAS  PubMed  Article  Google Scholar 

  5. Ali EA, Barakat BM, Hassan R (2015) Antioxidant and angiostatic effect of Spirulina platensis suspension in complete Freund’s adjuvant-induced arthritis in rats. PLoS ONE 10(4):e0121523

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  6. Anwer R, Khursheed S, Fatma T (2012) Detection of immunoactive insulin in Spirulina. J Appl Phycol 24:583–591

    CAS  Article  Google Scholar 

  7. Bai SK, Lee SJ, Na HJ et al (2005) beta-Carotene inhibits inflammatory gene expression in lipopolysaccharide-stimulated macrophages by suppressing redox-based NF-kappaB activation. Exp Mol Med 37(4):323–334

    CAS  PubMed  Article  Google Scholar 

  8. Banji D, Banji OJ, Pratusha NG et al (2013) Investigation on the role of Spirulina platensis in ameliorating behavioural changes, thyroid dysfunction and oxidative stress in offspring of pregnant rats exposed to fluoride. Food Chem 140(1–2):321–331

    CAS  PubMed  Article  Google Scholar 

  9. Beheshtipour H, Mortazavian AM, Haratian P et al (2012) Effects of Chlorella vulgaris and Arthrospira platensis addition on viability of probiotic bacteria in yogurt and its biochemical properties. Eur Food Res Technol 235(4):719–728

    CAS  Article  Google Scholar 

  10. Ben Abdallah Kolsi R, Ben Gara A, Chaaben R et al (2015) Anti-obesity and lipid lowering effects of Cymodocea nodosa sulphated polysaccharide on high cholesterol-fed-rats. Arch Physiol Biochem 121(5):210–217

    CAS  PubMed  Article  Google Scholar 

  11. Bergé JP, Debiton E, Dumay J et al (2002) In vitro anti-inflammatory and anti-proliferative activity of sulfolipids from the red alga Porphyridium cruentum. J Agric Food Chem 50(21):6227–6232

    PubMed  Article  CAS  Google Scholar 

  12. Bermejo P, Piñero E, Villar ÁM (2008) Iron-chelating ability and antioxidant properties of phycocyanin isolated from a protean extract of Spirulinaplatensis. Food Chem 110(2):436–445

    CAS  PubMed  Article  Google Scholar 

  13. Bermejo-Bescós P, Piñero-Estrada E, Villar del Fresno AM (2008) Neuroprotection by Spirulina platensis protean extract and phycocyanin against iron-induced toxicity in SH-SY5Y neuroblastoma cells. Toxicol In Vitro 22:1496–1502

    PubMed  Article  CAS  Google Scholar 

  14. Chamorro G, Salazar M, Pages N (1996) Dominant lethal study of Spirulina maxima in male and female rats after short-term feeding. Phytother Res 10:28–32

    Article  Google Scholar 

  15. Chamorro G, Salazar M, Araújo KG et al (2002) Update on the pharmacology of Spirulina (Arthrospira), an unconventional food. Arch Latinoam Nutr 52(3):232–240

    PubMed  Google Scholar 

  16. Chen JC, Liu KS, Yang TJ et al (2012) Spirulina and C-phycocyanin reduce cytotoxicity and inflammation-related genes expression of microglial cells. Nutr Neurosci 15(6):252–256

    CAS  PubMed  Article  Google Scholar 

  17. Chen HW, Yang TS, Chen MJ et al (2014) Purification and immunomodulating activity of C-phycocyanin from Spirulina platensis cultured using power plant flue gas. Process Biochem 49:1337–1344

    CAS  Article  Google Scholar 

  18. Cherdkiatikul T, Suwanwong Y (2014) Production of the α and β subunits of Spirulina Allophycocyanin and C-Phycocyanin in Escherichia coli: a Comparative study of their antioxidant activities. J Biomol Screen 19(6):959–965

    PubMed  Article  CAS  Google Scholar 

  19. Cingi C, Conk-Dalay M, Bal C et al (2008) The effects of spirulina on allergic rhinitis. Eur Arch Otorhinolaryngol 265:1219–1223

    PubMed  Article  Google Scholar 

  20. Dar BA, KhaliqR JG et al (2014) Protective effects of dietary spirulina against cadmium chloride exposed histoarchitectural changes in the liver of freshwater catfish Clarias batrachus (Linnaeus, 1758). Indian J Fish 61(3):83–87

    Google Scholar 

  21. Dartsch PC (2008) Antioxidant potential of selected Spirulina platensis preparations. Phytother. Res. 22(5):627–633

    PubMed  Article  Google Scholar 

  22. Das UN (2007) γ-Linolenic acid therapy of human glioma-a review of in vitro, in vivo, and clinical studies. Med Sci Monit 13(7):119–131

    Google Scholar 

  23. Deng R, Chow TJ (2010) Hypolipidemic, antioxidant and antiinflammatory activities of microalgae spirulina. Cardiovasc Ther 28(4):e33–e45

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  24. Ding J, Jin A, Shi L et al (2004) Effect of spirulina on antioxdation ability of liver during CCl4 induced chronic liver injury in mice. J Lake Sci 16(4):343–348

    Google Scholar 

  25. Dohnal V, Wu Q, Kuca K (2014) Metabolism of aflatoxins: key enzymes and interindividual as well as interspecies differences. Arch Toxic 88:1634–1644

    Article  CAS  Google Scholar 

  26. Domingueti CP, Dusse LM, Carvalho MD, et al (2015) Diabetes mellitus: the linkage between oxidative stress, inflammation, hypercoagulability and vascular complications. J Diabetes Complications. doi:10.1016/j.jdiacomp.2015.12.018. [Epub ahead of print]

  27. DSHEA (1994) Dietary Supplement Health and Education Act. Public Law 103-417. http://www.health.gov/dietsupp/ch1.htm. Accessed 5 April 2016

  28. DSLD (2009) Dietary Supplements Labels Database. http://dietarysupplements.nlm.nih.gov/dietary/index.jsp. Accessed 5 April 2016

  29. El Baz FK, El Baroty GS, Abd El Baky HH et al (2013) Structural characterization and biological activity of sulfolipids from selected marine algae. Grasas Aceites 64(5):561–571

    Article  CAS  Google Scholar 

  30. El Sheikh SM, Shalaby MAM, Hafez RA et al (2014) The immunomodulatory effects of probiotic bacteria on peripheral blood mononuclear cells (PBMCS) of allergic patients. Am J Immunol 10(3):116–130

    Article  Google Scholar 

  31. Electronic Code of Federal Regulations (2016) Title 21, Chapter I, Subchapter A, Part 73, Subpart A, §73.530. http://www.ecfr.gov/cgi-bin/text-idx?mc=true&tpl=true&tpl=ecfrbroowse/Title21/21cfr73_main_02.tpl. Accessed 5 April 2016

  32. Elshazly MO, Abd El-Rahman SS, Morgan AM et al (2015) The remedial efficacy of Spirulina platensis versus chromium-induced nephrotoxicity in male sprague-dawley rats. PLoS ONE 10(6):e0126780

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  33. El-Tantawy WH (2015) Antioxidant effects of Spirulina supplement against lead acetate-induced hepatic injury in rats. J Traditional Complem Med. doi:10.1016/j.jtcme.2015.02.001

    Google Scholar 

  34. European Advisory Services (2007) The use of substances with nutritional or physiological effect other than vitamins and minerals in food supplements. Study undertaken for DG SANCO, European Comission. http://ec.europa.eu/food/safety/docs/labellingnutrition-supplements-2007_a540169_study_other_substances_en.pdf. Accessed 5 April 2016

  35. Farina M, Soares FA, Zeni G et al (2004) Additive prooxidative effect of methylmercury and ebselen in liver from suckling rat pups. Toxicol Lett 146(3):227–235

    CAS  PubMed  Article  Google Scholar 

  36. FDA (2003) Agency Response Letter GRAS Notice No.GRN 000127. http://www.fda.gov/Food/FoodIngredientsPackaging/GenerallyRecognizedasSafeGRAS/GRASListings/ucm153944.htm. Accessed 5 April 2016

  37. Fournier DB, Gordon GB (2000) COX-2 and colon cancer: potential targets for chemoprevention. J Cell Biochem Suppl 34:97–102

    CAS  PubMed  Article  Google Scholar 

  38. Gad AS, Khadrawy YA, El-Nekeety AA et al (2011) Antioxidant activity and hepatoprotective effects of whey protein and Spirulina in rats. Nutrition 27(5):582–589

    CAS  PubMed  Article  Google Scholar 

  39. GB/T 16919-1997. Food grade Spirulina powder. http://www.tsinfo.js.cn/inquiry/gbtdetails.aspx?A100=GB/T%2016919-1997. Accessed 5 April 2016

  40. González R, Rodríguez S, Romay C et al (1999) Anti-inflammatory activity of phycocyanin extract in acetic acid-induced colitis in rats. Pharmacol Res 39(1):55–59

    PubMed  Article  Google Scholar 

  41. Gupta NK, Gupta KP (2012) Effects of C-Phycocyanin on the representative genes of tumor development in mouse skin exposed to 12-O-tetradecanoyl-phorbol-13-acetate. Environ Toxicol Pharmacol 34(3):941–948

    CAS  PubMed  Article  Google Scholar 

  42. Gurbuz N, Coskun ZK, Omeroglu S et al (2013) Antioxidative and therapeutic effects of spirulina on trichloroethylene induced cutaneous irritation balb/c mice. Bratisl Lek Listy 114(4):192–198

    CAS  PubMed  Google Scholar 

  43. Gutiérrez-Rebolledo GA, Galar-Martínez M, García-Rodríguez RV, Chamorro-Cevallos GA et al (2015) Antioxidant effect of Spirulina (Arthrospira) maxima on chronic inflammation induced by Freund’s complete adjuvant in rats. J Med Food 18(8):865–871

    PubMed  Article  Google Scholar 

  44. Hassan AM, Abdel-Aziem SH, Abdel-Wahhab MA (2012) Modulation of DNA damage and alteration of gene expression during aflatoxicosis via dietary supplementation of Spirulina (Arthrospira) and Whey protein concentrate. Ecotoxicol Environ Saf 79:294–300

    CAS  PubMed  Article  Google Scholar 

  45. Health Canada (2008). Blue green algae (Cyanobacteria) and their toxins. http://www.hc-sc.gc.ca/ewh-semt/pubs/water-eau/cyanobactereng.php. Accessed 5 April 2016

  46. Hirahashi T, Matsumoto M, Hazeki K et al (2002) Activation of the human innate immune system by Spirulina: augmentation of interferon production and NK cytotoxicity by oral administration of hot water extract of Spirulina platensis. Int Immunopharmacol 2(4):423–434

    CAS  PubMed  Article  Google Scholar 

  47. Hirata T, Tanaka M, Ooike M et al (1999) Radical scavenging activities of phycocyanobilin prepared from a cyanobacterium, Spirulina platensis. Fisheries Sci 65:971–972

    CAS  Google Scholar 

  48. Hirata T, Tanaka M, Ooike M et al (2000) Antioxidant activities of phycocyanobilin prepared from Spirulina platensis. J Appl Phycol 12:435–439

    CAS  Article  Google Scholar 

  49. Hoang MH, Kim JY, Lee JH et al (2015) Antioxidative, hypolipidemic, and anti-inflammatory activities of sulfated polysaccharides from Monostroma nitidum. Food Sci Biotechnol 24(1):199–205

    CAS  Article  Google Scholar 

  50. Hoseini SM, Khosravi-Darani K, Mozafari MR (2013) Nutritional and medical applications of spirulina microalgae. Mini Rev Med Chem 13(8):1231–1237

    CAS  Article  Google Scholar 

  51. Huang Z, Guo BJ, Wong RNS et al (2007) Characterization and antioxidant activity of selenium-containing phycocyanin isolated from Spirulina platensis. Food Chem 100:1137–1143

    CAS  Article  Google Scholar 

  52. Hwang JH, Chen JC, Yang SY et al (2011a) Expression of COX-2 and NMDA receptor genes at the cochlea and midbrain in salicylate induced tinnitus. Laryngoscope 121:361–364

    CAS  PubMed  Article  Google Scholar 

  53. Hwang JH, Lee IT, Jeng KC et al (2011b) Spirulina prevents memory dysfunction, reduces oxidative stress damage and augments antioxidant activity in senescence-accelerated mice. J Nutr Sci Vitaminol 57(2):186–191

    CAS  PubMed  Article  Google Scholar 

  54. Hwang JH, Chen JC, Chan YC (2013) Effects of C-phycocyanin and Spirulina on salicylate-induced tinnitus, expression of NMDA receptor and inflammatory genes. PLoS ONE 8(3):e58215

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  55. Ibrahim AE, Abdel-Daim MM (2015) Modulating Effects of Spirulina platensis against Tilmicosin-induced cardiotoxicity in mice. Cell J 17(1):137–144

    PubMed  PubMed Central  Google Scholar 

  56. Ismail M, Hossain MF, Tanu AR et al (2015) Effect of spirulina intervention on oxidative stress, antioxidant status, and lipid profile in chronic obstructive pulmonary disease patients. Biomed Res Int 2015:486120

    PubMed  PubMed Central  Google Scholar 

  57. Jeyaprakash K, Chinnaswamy P (2007) Antioxidant property of Spirulina and Liv-52 against lead induced toxicity in albino rats. J Nat Remed 7(1):80–85

    Google Scholar 

  58. Kalafati M, Jamurtas AZ, Nikolaidis MG et al (2010) Ergogenic and antioxidant effects of spirulina supplementation in humans. Med Sci Sports Exerc 2(1):142–151

    Article  Google Scholar 

  59. Karkos PD, Leong SC, Karkos CD et al (2011) Spirulina in clinical practice: evidence-based human applications. Evid Based Complement Alternat Med 2011:531053

    CAS  PubMed  Article  Google Scholar 

  60. Katsuura S, Imamura T, Bando N et al (2009) beta-Carotene and beta-cryptoxanthin but not lutein evoke redox and immune changes in RAW264 murine macrophages. Mol Nutr Food Res 53(11):1396–1405

    CAS  PubMed  Article  Google Scholar 

  61. Khan Z, Bhadouria P, Bisen PS (2005) Nutritional and therapeutic potential of Spirulina. Curr Pharm Biotechnol 6(5):373–379

    CAS  PubMed  Article  Google Scholar 

  62. Khan M, Varadharaj S, Ganesan LP et al (2006) C-phycocyanin protects against ischemia-reperfusion injury of heart through involvement of p38 MAPK and ERK signaling. Am J Physiol Heart Circ Physiol 290(5):2136–2145

    Article  CAS  Google Scholar 

  63. Kim MY, Cheong SH, Lee JH et al (2010) Spirulina improves antioxidant status by reducing oxidative stress in rabbits fed a high-cholesterol diet. J Med Food 13(2):420–426

    CAS  PubMed  Article  Google Scholar 

  64. Kim SS, Rahimnejad S, Kim KW et al (2013) Effects of dietary supplementation of spirulina and quercetin on growth, innate immune responses, disease resistance against edwardsiella tarda, and dietary antioxidant capacity in the juvenile olive flounder paralichthys olivaceus. Fish Aquat Sci 16(1):7–14

    CAS  Google Scholar 

  65. Koníčková R, Vaňková K, Vaníková J et al (2014) Anti-cancer effects of blue-green alga Spirulina platensis, a natural source of bilirubin-like tetrapyrrolic compounds. Ann Hepatol 13(2):273–283

    PubMed  Google Scholar 

  66. Kris-Etherton P, Harris W, Appel LJ (2003) Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Arterioscler Thromb Vasc Biol 23:20–30

    Article  Google Scholar 

  67. Kulshreshtha A, Zacharia AJ, Jarouliya U et al (2008) Spirulina in health care management. Curr Pharm Biotechnol 9(5):400–405

    CAS  PubMed  Article  Google Scholar 

  68. Langers I, Renoux VM, Thiry M et al (2012) Natural killer cells: role in local tumor growth and metastasis. Biologics 6:73–82

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Lanone S, Bloc S, Foresti R et al (2005) Bilirubin decreases nos2 expression via inhibition of NAD(P)H oxidase: implications for protection against endotoxic shock in rats. FASEB J 19:1890–1892

    CAS  PubMed  Google Scholar 

  70. Lee JB, Hayashi T, Hayashi K et al (1998) Further purification and structural analysis of calcium spirulan from Spirulina platensis. J Nat Prod 61:1101–1104

    CAS  PubMed  Article  Google Scholar 

  71. Lee EH, Park JE, Choi YJ et al (2008) A randomized study to establish the effects of spirulina in type 2 diabetes mellitus patients. Nutr Res Pract 2(4):295–300

    PubMed  PubMed Central  Article  Google Scholar 

  72. Li XL, Xu G, Chen T et al (2009) Phycocyanin protects INS-1E pancreatic beta cells against human islet amyloid polypeptide-induced apoptosis through attenuating oxidative stress and modulating JNK and p38 mitogen-activated protein kinase pathways. Int J Biochem Cell Biol 41(7):1526–1535

    CAS  PubMed  Article  Google Scholar 

  73. Liu YF, Xu LZ, Cheng N et al (2000) Inhibitory effect of phycocyanin from Spirulina platensis on the growth of human leukemia K562 cells. J Appl Phycol 12:125–130

    CAS  Article  Google Scholar 

  74. Lorenz RT (1999) A review of Spirulina and Haematococcus algae meal as a carotenoid and vitamin supplement for poultry. Spirulina Pacifica Tech Bull 53:1–14

    Google Scholar 

  75. Lu HK, Hsieh CC, Hsu JJ et al (2006) Preventive effects of Spirulina platensis on skeletal muscle damage under exercise-induced oxidative stress. Eur J Appl Physiol 98(2):220–226

    PubMed  Article  Google Scholar 

  76. Lu YM, Xiang WZ, Wen YH (2011) Spirulina (Arthrospira) industry in Inner Mongolia of China: current status and prospects. J Appl Phycol 23:265–269

    PubMed  Article  Google Scholar 

  77. Mader J, Gallo A, Schommartz T et al (2016) Calcium spirulan derived from Spirulina platensis inhibits herpes simplex virus 1 attachment to human keratinocytes and protects against herpes labialis. J Allergy Clin Immunol 137(1):197–203

    CAS  PubMed  Article  Google Scholar 

  78. Mahendra J, Mahendra L, Muthu J et al (2013) Clinical effects of subgingivally delivered spirulina gel in chronic periodontitis cases: a placebo controlled clinical trial. J Clin Diagn Res 7(10):2330–2333

    PubMed  PubMed Central  Google Scholar 

  79. Mallikarjun Gouda KG, Udaya Sankar K, Sarada R et al (2015) Supercritical CO2 extraction of functional compounds from Spirulina and their biological activity. J Food Sci Technol 52(6):3627–3633

    CAS  Google Scholar 

  80. Mao TK, Van De Water J, Gershwin ME (2000) Effect of spirulina on the secretion of cytokines from peripheral blood mononuclear cells. J Med Food 3(3):135–140

    CAS  PubMed  Article  Google Scholar 

  81. Mao TK, Van de Water J, Gershwin ME (2005) Effects of a Spirulina-based dietary supplement on cytokine production from allergic rhinitis patients. J Med Food 8(1):27–30

    CAS  PubMed  Article  Google Scholar 

  82. Marles RJ, Barrett ML, Barnes J et al (2011) United States pharmacopeia safety evaluation of spirulina. Crit Rev Food Sci Nutr 51(7):593–604

    CAS  PubMed  Article  Google Scholar 

  83. Matsumoto H, Ishikawa K, Itabe H et al (2006) Carbon monoxide and bilirubin from heme oxygenase-1 suppresses reactive oxygen species generation and plasminogen activator inhibitor-1 induction. Mol Cell Biochem 291:21–28

    CAS  PubMed  Article  Google Scholar 

  84. McCarty MF (2007) Clinical potential of spirulina as a source of phycocyanobilin. J Med Food 10:566–570

    CAS  PubMed  Article  Google Scholar 

  85. McElhaney JE, Kuchel GA, Zhou X et al (2016) T-Cell immunity to influenza in older adults: a pathophysiological framework for development of more effective vaccines. Front Immunol 7:41

    PubMed  PubMed Central  Article  Google Scholar 

  86. MHRA (2009) Medicines and Healthcare products Regulatory Agency, UK. Data on suspected adverse drug reactions. http://www.mhra.gov.uk//Onlineservices/Medicines/Druganalysisprints/index.htm. Accessed 5 April 2016

  87. Miranda MS, Cintra RG, Barros SB et al (1998) Antioxidant activity of the microalga Spirulina maxima. Braz J Med Biol Res 31:1075–1079

    CAS  PubMed  Article  Google Scholar 

  88. Mitra S, Siddiqui WA, Khandelwal S (2015) C-Phycocyanin protects against acute tributyltin chloride neurotoxicity by modulating glial cell activity along with its anti-oxidant and anti-inflammatory property: a comparative efficacy evaluation with N-acetyl cysteine in adult rat brain. Chem Biol Interact 238:138–150

    CAS  PubMed  Article  Google Scholar 

  89. Muga MA, Chao JC (2014) Effects of fish oil and spirulina on oxidative stress and inflammation in hypercholesterolemic hamsters. BMC Complement Altern Med 14:470

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  90. Nakagawa H, Montgomery WL (2007) Algae. In: Dietary supplements for the health and quality of cultured fish. Edited by Nakagawa H, Sato S. and Gatlin III. D. CABI North American Office Cambridge, MA 02139 USA, 133–168

  91. Ngo-Matip ME, Pieme CA, Azabji-Kenfack M et al (2015) Impact of daily supplementation of Spirulina platensis on the immune system of naïve HIV-1 patients in Cameroon: a 12-months single blind, randomized, multicenter trial. Nutr J 14:70

    PubMed  PubMed Central  Article  Google Scholar 

  92. Pabon MM, Jernberg JN, Morganti J et al (2012) A spirulina-enhanced diet provides neuroprotection in an α-synuclein model of Parkinson’s disease. PLoS ONE 7(9):e45256

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  93. Pak W, Takayama F, Mine M, Nakamoto K et al (2012) Anti-oxidative and anti-inflammatory effects of spirulina on rat model of non-alcoholic steatohepatitis. J Clin Biochem Nutr 51(3):227–234

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Park HJ, Lee YJ, Ryu HK et al (2008) A randomized double-blind, placebo-controlled study to establish the effects of spirulina in elderly Koreans. Ann Nutr Metab 52(4):322–328

    CAS  PubMed  Article  Google Scholar 

  95. Patil S, Al-Zarea BK, Maheshwari S et al (2015) Comparative evaluation of natural antioxidants spirulina and aloe vera for the treatment of oral submucous fibrosis. J Oral Biol Craniofac Res 5(1):11–15

    PubMed  PubMed Central  Article  Google Scholar 

  96. Pham TX, Kim B, Lee J (2013) Spirulina platensis inhibits lipopolysaccharide-induced inflammation through the repression of histone deacetylases in RAW 264.7 macrophages. FASEB J 27:1

    Article  CAS  Google Scholar 

  97. Ponce-Canchihuamán JC, Pérez-Méndez O, Hernández-Muñoz R et al (2010) Protective effects of Spirulina maxima on hyperlipidemia and oxidative-stress induced by lead acetate in the liver and kidney. Lipids Health Dis 9:1–7

    Article  Google Scholar 

  98. Priyadarshani I, Rath B (2012) Commercial and industrial applications of micro algae—a review. J Algal Biomass Utln 3(4):89–100

    Google Scholar 

  99. Qing R, Ye H, Lan L, Fu H (2003) Study of the activity of two antioxidant enzymes of Spirulina maxima under excessive light stress. J Sichuan Univ 40(3):565–569

    Google Scholar 

  100. Qureshi MA, Ali RA (1996) Spirulina platensis exposure enhances macrophage phagocytic function in cats. Immunopharmacol Immunotoxicol 18:457–463

    CAS  PubMed  Article  Google Scholar 

  101. Radman M, Golshiri A, Shamsizadeh A et al (2015) Toll-like receptor 4 plays significant roles during allergic rhinitis. Allergol Immunopathol 43(4):416–420

    CAS  Article  Google Scholar 

  102. Rasool M, Sabina EP (2009) Appraisal of immunomodulatory potential of Spirulina fusiformis: an in vivo and in vitro study. J Nat Med 63(2):169–175

    PubMed  Article  Google Scholar 

  103. Rasool M, Sabina EP, Lavanya B (2006) Anti-inflammatory effect of Spirulina fusiformis on adjuvant-induced arthritis in mice. Biol Pharm Bull 29(12):2483–2487

    CAS  PubMed  Article  Google Scholar 

  104. Rasool MK, Sabina EP, Nithya P, Lavanya K (2009) Suppressive effect of Spirulina fusiformis in relation to lysosomal acid hydrolases, lipid peroxidation, antioxidant status, and inflammatory mediator TNF-alpha on experimental gouty arthritis in mice. Orient Pharm Exp Med 9(2):164–173

    Article  Google Scholar 

  105. Reddy CM, Bhat VB, Kiranmai G et al (2000) Selective inhibition of cyclooxygenase-2 by C-phycocyanin, a biliprotein from Spirulina platensis. Biochem Biophys Res Commun 277(3):599–603

    CAS  PubMed  Article  Google Scholar 

  106. Remirez D, González R, Merino N et al (2002) Inhibitory effects of Spirulina in zymosan-induced arthritis in mice. Mediators Inflamm 11(2):75–79

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  107. Riss J, Décordé K, Sutra T et al (2007) Phycobiliprotein C-phycocyanin from Spirulina platensis is powerfully responsible for reducing oxidative stress and NADPH oxidase expression induced by an atherogenic diet in hamsters. J Agric Food Chem 55(19):7962–7967

    CAS  PubMed  Article  Google Scholar 

  108. Romay C, Gonzalez R, Ledon N et al (2003) Cphycocyanin: a biliprotein with antioxidant, anti-inflammatory and neuroprotective effects. Curr Protein Pept Sci 4:207–216

    CAS  PubMed  Article  Google Scholar 

  109. Sagara T, Nishibori N, Kishibuchi R et al (2015) Non-protein components of Arthrospira (Spirulina) platensis protect PC12 cells against iron-evoked neurotoxic injury. J Appl Phycol 27(2):849–855

    CAS  Article  Google Scholar 

  110. Sanyal AJ (2001) Nonalcoholic steatohepatitis. Indian J Gastroenterol 20:64–70

    Google Scholar 

  111. Schafer FQ, Wang HP, Kelley EE et al (2002) Comparing beta-carotene, vitamin E and nitric oxide as membrane antioxidants. Biol Chem 383(3–4):671–681

    CAS  PubMed  Google Scholar 

  112. Selmi C, Leung PS, Fischer L et al (2011) The effects of Spirulina on anemia and immune function in senior citizens. Cell Mol Immunol 8(3):248–254

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  113. Shalaby EA, Shanab SMM (2013) Comparison of DPPH and ABTS assays for determining antioxidant potential of water and methanol extracts of Spirulina platensis. Indian J Geo Marine Sci 42(5):556–564

    Google Scholar 

  114. Sharma KM, Sharma A, Kumar A et al (2007) Spirulina fusiformis provides protection against mercuric chloride induced oxidative stress in Swiss albino mice. Food Chem Toxicol 45:2412–2419

    CAS  PubMed  Article  Google Scholar 

  115. Sharma S, Yadav N, Pandey A et al (2013) Antioxidant rich diet supplements (Spirulina and tamarind fruit pulp) mitigate hematological disorders in fluoride exposed mice. Toxicol Environ Chem 95(10):1739–1747

    CAS  Article  Google Scholar 

  116. Shetty P, Shenai P, Chatra L et al (2013) Efficacy of spirulina as an antioxidant adjuvant to corticosteroid injection in management of oral submucous fibrosis. Indian J Dent Res 24(3):347–350

    PubMed  Article  Google Scholar 

  117. Shokri H, Khosravi A, Taghavi M (2014) Efficacy of Spirulina platensis on immune functions in cancer mice with systemic candidiasis. J Mycol Res 1(1):7–13

    Google Scholar 

  118. Sin JB, Choi WY, Lee HY (2014) Comparison of anti-inflammatory activity of Spirulina maxima extract by ultrasonication and water extraction process Spirulina maxima. J Korean Soc Food Nutr 43(12):1852–1857

    CAS  Article  Google Scholar 

  119. Small E (2011) Spirulina-food for the universe. Biodiversity 12(4):255–265

    Article  Google Scholar 

  120. Soheili M, Khosravi-Darani K (2011) The potential health benefits of algae and micro algae in medicine: a review on Spirulina platensis. Curr Nutr Food Sci 27(4):279–285

    Article  Google Scholar 

  121. Somchit MN, Mohamed NA, Ahmad Z et al (2014) Anti-inflammatory and anti-pyretic properties of Spirulina platensis and Spirulina lonar: a comparative study. Pak J Pharm Sci 27(5):1277–1280

    PubMed  Google Scholar 

  122. Sotiroudis TG, Sotiroudis GT (2013) Health aspects of Spirulina (Arthrospira) microalga food supplement. J Serb Chem Soc 78(3):395–405

    CAS  Article  Google Scholar 

  123. Sudharsan S, Subhapradha N, Seedevi P et al (2015) Antioxidant and anticoagulant activity of sulfated polysaccharide from Gracilaria debilis (Forsskal). Int J Biol Macromol 81:1031–1038

    CAS  PubMed  Article  Google Scholar 

  124. Teng YN, Sheu MJ, Hsieh YW et al (2016) Beta-carotene reverses multidrug resistant cancer cells by selectively modulating human P-glycoprotein function. Phytomedicine 23(3):316–323

    CAS  PubMed  Article  Google Scholar 

  125. TGA (2005) Therapeutic Goods Administration, Australia. Complementary Medicin-es Evaluation Committee 52nd meeting. August 2005. http://www.tga.gov.au/docs/pdf/cmec/cmecmi52.pdf. Accessed 5th April 2016

  126. Tobón-Velasco JC, Palafox-Sánchez V, Mendieta L et al (2013) Antioxidant effect of Spirulina (Arthrospira) maxima in a neurotoxic model caused by 6-OHDA in the rat striatum. J Neural Transm 120(8):1179–1189

    PubMed  Article  CAS  Google Scholar 

  127. Upasani CD, Balaraman R (2003) Protective effect of Spirulina on lead induced deleterious changes in the lipid peroxidation and endogenous antioxidants in rats. Phytother Res 17:330–334

    CAS  PubMed  Article  Google Scholar 

  128. Vázquez-Velasco M, González-Torres L, López-Gasco P et al (2014) Liver oxidation and inflammation in Fa/Fa rats fed glucomannan/spirulina-surimi. Food Chem 159:215–221

    PubMed  Article  CAS  Google Scholar 

  129. Vidé J, Virsolvy A, Romain C et al (2015a) Dietary silicon-enriched spirulina improves early atherosclerosis markers in hamsters on a high-fat diet. Nutrition 31(9):1148–1154

    PubMed  Article  CAS  Google Scholar 

  130. Vidé J, Romain C, Feillet-Coudray C et al (2015b) Assessment of potential toxicological aspects of dietary exposure to silicon-rich spirulina in rats. Food Chem Toxicol 80:108–113

    PubMed  Article  CAS  Google Scholar 

  131. Vo TS, Ryu B, Kim SK (2013) Purification of novel anti-inflammatory peptides from enzymatic hydrolysate of the edible microalgal Spirulina maxima. J Funct foods 5:1336–1346

    CAS  Article  Google Scholar 

  132. Walker DM (2004) Oral mucosal immunology: an overview. Ann Acad Med Singapore 33(Suppl):27S–30S

    Google Scholar 

  133. Wang L, Pan B, Sheng J et al (2007) Antioxidant activity of Spirulina platensis extracts by supercritical carbon dioxide extraction. Food Chem 105:36–41

    CAS  Article  Google Scholar 

  134. Wang X, Liu Q, Ihsan A et al (2012) JAK/STAT pathway plays a critical role in the proinflammatory gene expression and apoptosis of RAW264.7 cells induced by trichothecenes as DON and T-2 toxin. Toxicol Sci 127:412–424

    CAS  PubMed  Article  Google Scholar 

  135. Wang L, Wang X, Wu H et al (2014a) Overview on biological activities and molecular characteristics of sulfated polysaccharides from marine green algae in recent years. Mar Drugs 12(9):4984–5020

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  136. Wang Z, Wu Q, Kuca K et al (2014b) Deoxynivalenol: signaling pathways and human exposure risk assessment—an update. Arch Toxicol 88:1915–1928

    CAS  PubMed  Article  Google Scholar 

  137. Wu LC, Ho JA, Shieh MC et al (2005) Antioxidant and antiproliferative activities of Spirulina and Chlorella water extracts. J Agric Food Chem 53(10):4207–4212

    CAS  PubMed  Article  Google Scholar 

  138. Wu Q, Wang X, Yang W et al (2014a) Oxidative stress mediated cytotoxicity and metabolism of T-2 toxin and deoxynivalenol in animals and humans: an update. Arch Toxicol 88:1309–1326

    CAS  PubMed  Article  Google Scholar 

  139. Wu Q, Wang X, Wan D et al (2014b) Crosstalk of JNK1-STAT3 is critical for RAW264.7 cell survival. Cell Signal 26:2951–2960

    CAS  PubMed  Article  Google Scholar 

  140. Xia D, Liu B, Luan XY et al (2016) Protective effects of C-phycocyanin on alcohol-induced acute liver injury in mice. Chin J Oceanol Limnol 34(2):399–404

    CAS  Article  Google Scholar 

  141. Yang LL, Zhou QJ, Wang Y et al (2012) Comparison of the therapeutic effects of extracts from Spirulina platensis and amnion membrane on inflammation-associated corneal neovascularization. Int J Ophthalmol. 5(1):32–37

    CAS  PubMed  PubMed Central  Google Scholar 

  142. Yang F, Wong KH, Yang Y et al (2014) Purification and in vitro antioxidant activities of tellurium-containing phycobiliproteins from tellurium-enriched Spirulina platensis. Drug Des Devel Ther 8:1789–1800

    CAS  PubMed  PubMed Central  Google Scholar 

  143. Yogianti F, Kunisada M, Nakano E et al (2014) Inhibitory effects of dietary Spirulina platensis on UVB-induced skin inflammatory responses and carcinogenesis. J Invest Dermatol 134(10):2610–2619

    CAS  PubMed  Article  Google Scholar 

  144. Yoshikawa T, Naito Y (2002) What is oxidative stress. JMAJ 45(7):271–276

    Google Scholar 

  145. Youn K, Lee J, Yun EY et al (2014) Biological evaluation and in silico docking study of gamma-linolenic acid as a potential BACE1 inhibitor. J Funct Foods 10:187–191

    CAS  Article  Google Scholar 

  146. Zheng J, Inoguchi T, Sasaki S et al (2013) Phycocyanin and phycocyanobilin from Spirulina platensis protect against diabetic nephropathy by inhibiting oxidative stress. Am J Physiol Regul Integr Comp Physiol 304(2):R110–R112

    CAS  PubMed  Article  Google Scholar 

  147. Zhou ZP, Liu LN, Chen XL et al (2005) Factors that effect antioxidant activity of C-phycocyanins from Spirulina platensis. J Food Biochem 29:313–322

    CAS  Article  Google Scholar 

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Acknowledgments

This work was financially supported by Yangtze Youth Talents Fund (Yangtze University, Grant No. 2015cqr19), National Natural Science Foundation of China (81501269), the project of Excellence FIM UHK, as well as the long-term development plan UHHK.

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Correspondence to Qinghua Wu or Kamil Kuča.

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Wu, Q., Liu, L., Miron, A. et al. The antioxidant, immunomodulatory, and anti-inflammatory activities of Spirulina: an overview. Arch Toxicol 90, 1817–1840 (2016). https://doi.org/10.1007/s00204-016-1744-5

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Keywords

  • Spirulina
  • Phycocyanin
  • Antioxidant
  • Immunomodulation
  • Anti-inflammatory
  • Mechanism of action