Spirulina is a high quality source of proteins, pigments, minerals, vitamins. It has special properties in food and drug industries. It’s role proved to potentiate the immune system leading for prevent of cancer development, viral infection, inflammatory, allergy and immunodeficiency, increase activity of macrophages, stimulating the production of antibodies and cytokines, activation of B and T cells and immune modulation effect. In addition Spirulina supplements have a greater effect on innate immunity by improving the activity of NK cells. Spirulina can be a healthy and functional diet with potential impacts on immunity, thus the effect of food containing it should be evaluated in the future. Aim of this review is exhibit knowledge regarding the character of this microalga in human immune system.

 

Keywords: Spirulina, Immune system, Antioxidant, Antibodies

There is interest in using antioxidants because it protects cells and tissues from oxidative damage and free radical [1]. In the mid-1980s, extensive research and development efforts have been made to develop nutritious and functional foods for the prevention and management of various diseases [2-5]. Spirulina look at as the most prophylactic and healing nutritional requirements in this century [6]. It has superiority protein, minerals (K, Ca, Mg, Fe, Zn, Na), vitamins, particularly vitamin B12 and pro-vitamin (β-carotene), polyunsaturated fatty acids and other bioactive as molecules Include phenolic acids, tocopherols and γ-linoleic acid [7,8]. The unfamiliar or questionable activities of immune modulatory function of Spirulina were first determined by scientific observation in mice since 1994 [9]. Spirulina is produced in a widespread and make commercial as a dietary supplement for treatment of malnutrition and modulating immune functions, as well as increase a range of diseases [10]. Including obesity, hyperlipidemia, protection against some cancers, enhancement of the immune system, increment of intestinal lactobacilli, and decrease of nephrotoxicity by heavy metals and drugs, radiation protection [11]. Moreover, Spirulina contain many functional bioactive ingredients with antioxidant and anti-inflammatory, including phenolic phytochemicals [12,13] and the phycobiliprotein c-phycocyanin [14]. Therefore, purpose of this review aimed to evaluate the possibility that Spirulina could be an immune system activation, antioxidant and immunomodulation functional food on human evidences.

BIOLOGICAL AND MEDICAL APPLICATIONS

Spirulina is considered as one prophylactic and healing nutritional component in this century [6] due to its nutrient profile non-significant side effects [7] and therapeutic properties [15,16]. Earlier, due to plant pigments and its ability to photosynthesis, it was classified in the plant category. Later on the basis of biochemical properties, physiology and genetic understanding of the new, they were classified as realm of bacteria [17]. In fact, Spirulina is recognized for its high protein content (60-70% by dry weight) as well as vitamins, minerals, essential fatty acids and other nutrients [18-20]. Recent analyze indicate that blue-green alga is named as Spirulina platensis (Figure 1), may have a variety of health benefits and therapeutic properties and it has antioxidant and anti-inflammatory role [21]. Clinical tests have testified that Spirulina can serve as a supplementary for many diseases. Capsules of Spirulina showed effective in lowering blood lipids level and in decreasing white blood cells after radiotherapy and chemotherapy, as well as improving immunological function. [22,23]. It is a potential therapeutic material for oxidative stress-induced disorders [24]. Clinic trial suggest that Spirulina has certain therapeutic effects such as reduction in blood cholesterol, protection against some cancers, enhancement of the immune system, growth of intestinal lactobacilli, decrease of nephrotoxicity by heavy metals and medicines, radiation protection, fall of hyperlipidemia and fatness [11]. Also Spirulina pills and capsules, there are too pastries, blocks and Spirulina containing chocolate bars, sold as health food. Other products are applied for weight loss and as an aid for quitting drug-addictions [25]. Spirulina has got no side effects and is non-toxic in nature.

EFFECTS ANTIOXIDANT, ANTI-INFLAMMATORY AND IMMUNOSTIMULATING OF SPIRULINA

Immune systems are defense against pathogenic organisms such as bacteria, viruses, cancer cells and parasites and against a complex series of compounds that are distinguish as “foreign” or “non-self”. Cells or molecule recognized as non-self is attacked by immune system cells and the antibodies they produce. The immune system is a complex system that involves specific cells that interconnect with each other via chemical messengers called cytokines. Therefore, impairment of the immune system has far-reaching consequences in the body. The close connection between oxidative stress and life-style diseases is evident. Oxidative stress is in fact defined by the loss of balance between high levels of oxidation and antioxidant systems in the body. It not only causes problems such as DNA oxidative damage and lipid peroxidation, but is associated with physiological imbalance and intracellular signal transduction tuning [26]. Foods that increase blood cholesterol levels also affect the expression of antioxidant enzymes [27,28], while free radicals caused by oxidative stress have been damaged to cells and tissues and possibly lead to cancer and cardiovascular damage [29,30]. Spirulina has high Functional compounds values and lip soluble antioxidants (Table 1) [12-14,31-33]. The anti-inflammatory effects of Spirulina are due to its antioxidant activity. Most recently Abdel-Daim et al. [34] using Spirulina platensis powder (500 and 1000 mg/kg) for an hour prior to the injection of delta methrin (15 mg/kg) in mice observed a significant reduction of the pro inflammatory cytokine tumor necrosis factor-alpha (TNF-𝛼) in serum and at the same time an improvement of oxidative stress markers (malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and glutathione peroxidase (GPX)) in hepatic, renal, and brain tissues [34]. Carotenoids are also important antioxidants and it has been shown that the risk of developing types of cancer in the diet rich in carotenoids has been reduced [2]. C-phycocyanin is a major Bili protein source of Spirulina which has antioxidant and radical breakdown properties [35]. Phycocyanin may prevent cancer by scavenging DNA damaging agents such as peroxynitrite [36]. Also induced apoptosis of human chronic myeloid leukemia cell line-k562 [37]. Spirulina also contains phenolic acids, tocopherols and ß-carotene, all of which have anti-antioxidant properties [38].

SPIRULINA EFFECT ON COMPLEMENT SAFETY INDICATORS

The complement system consists of more than 35 types of serum proteins that have a very close and controlled relationship with each other and other immune system molecules. 9 of their main components are named from C-1 to C-9 and these compounds play a key role in innate and acquired immunity [39]. The most important biological tasks of the complement system include eliminating microorganisms through involvement in phagocytosis processes, inflammatory reactions, immunization complexes and induction and improvement of antibody responses [40]. In the experiment, the Spirulina algae were added to the fish diet. The results of the experiment showed that the levels of C3 and C4 complements in fish with diet containing 10% Spirulina were higher than the control group and showed a significant difference (P<0.05) with the control group [41]. Regarding the effect of Spirulina on the complement based on genotype, the level of C3 increased significantly after 16 weeks (P<0.05) even after placebo supplementation. However, in all groups the level of C3 after the addition of Spirulina was unchanged, after the use of Spirulina supplementation or placebo, the level of (P<0.05) C3 was only altered in people with genotype A and G. There was major Spirulina supplementation effect on C3 level (P<0.01) and also MCP-1 genotype × treatment for C3 (P<0.05) [42]. Therefore, the use of Spirulina as a safety stimulant improves the physiological response in the disease.

ANTI-CANCER EFFECTS OF ALGA SPIRULINA

In many tumors, there are NK, T cells and activated macrophages around the tumor which among these cells, T-cell lymphocytes shapes the most effective response. Spontaneous immune responses are very weak to suppress tumor growth, although the immune system detects abnormal proteins in tumor cells as tumor antigens. To overcome this problem, a variety of adjuvants, including toll-like receptor (TLR) ligands, are investigated to potentiate antitumor immunity [43]. Cytokines and Th17 cell produced IL-17, which plays a very important role in tumor progression in mice and humans. IL-6 and IL-23 are vital cytokines for the differentiation and proliferation of Th17 cells Studies have shown that Spirulina LPS (Bacterial lipopolysaccharides) is a very weak inducer of IL-6 and IL-23 and a strong anti-cancer immune suppression with suppression IL-17 induction by increasing IFN-γ production through the TLR4 pathway [44,45]. Spirulina as well as its tetrapyrrolic components showed a significant decrease in the promotion of pancreatic cancer. PCB (phycocyanobilin) Available in Spirulina has a structural similarity to bilirubin, which is a potent antioxidant. Indeed, Bilirubin's anticancer action is related to its effects on the mitochondria and the internal signal of the cell [46]. This condition supports the role of chemotherapy [47]. To the rats with liver cancer were given phycocyanin and it was observed that their survival rates have increased significantly. Phycocyanin probably has hematopoietic function that can increase the number of thymocytes, which in turn increases the body's natural resistance to cancer, bleeding, ulcers and other diseases [48,49]. It has been shown that phycocyanin to cause apoptosis in tumor cells through the production of ROS and reduce the Adjusting the expression of Bcl-2. Phycocyanin is also known as an anti-apoptotic molecule [50], as well as through inducing cytochrome c release from mitochondria into the cytosol and PARP cleavage [51].

Anti-viral effects of Spirulina

Many researchers have tried to find practical and efficient antiviral foods within natural resources. Initially, almost four decades ago, the effects of polysaccharide from seaweed on the virus replication were reported [52]. Hayashi et al. [48] reported the anti HSV-1 activity of aqueous extracts from S. platensis. Spirulina polysaccharides inhibit replication of several enveloped viruses such as herpes simplex virus, influenza virus, measles virus, mumps virus, human cytomegalovirus and HIV-1 [53-56]. Three compounds of Spirulina, which include Ca-Sp, Cyanovirin-N and sulpholipid, have antiviral activity in HIV [54-56]. Ca-Sp and Cynovirin-N appear to interfere with the host cell in the first stage of the viral cycle, while sulpholipid interfere with reverse transcription of HIV-RNA (Figure 2) [56]. Thus extracts may become useful therapeutics that could help AIDS patient’s longer normal lives. Moreover, when HIV-infected or HIV-negative undernourished children and HIV-infected adults were treated with Spirulina supplementation, clinical improvement was always detected, including weight increase, improvement of hematological parameters and decrease in the HIV viral load [57-59].

ALLERGY, RHINITIS AND IMMUNOMODULATION

Spirulina inhibits the release of histamine from mast cells and shows anti-inflammatory properties [60,61]. In a randomized clinical trial [62], individuals with allergic rhinitis were fed daily with placebo or Spirulina for 12 weeks. The levels of cytokines (IL4, IFN-γ and IL-2) that are important in regulating immunoglobulin (IgE) mediated allergy as well as the level of peripheral blood mononuclear cells were measured before and after feeding with Spirulina. The study showed that high dose of Spirulina significantly reduced IL-4 levels by 32%, demonstrating the protective effects of this microalga toward allergic rhinitis [63]. In another study in Turkey, in order to evaluate the efficacy and tolerability of Spirulina against placebo, treatment for patients with allergic rhinitis was performed. This study showed that taking Spirulina compared to placebo (P<0.001), significantly improved symptoms and physical findings such as sneezing, nasal discharge, congestion and itching [64]. The above studies suggest that Spirulina can modulate the immune system by covering nutritional deficiencies [65]. Each of the four symptoms that were compared and evaluated for the use of Spirulina with placebo showed a significant improvement in each of the symptoms. For example, at the start of the study there was no significant difference in mean baseline values of both symptoms and physical findings of both groups (p more than 0.05 which mean non-significant correlation). The placebo group rated symptoms at 2.84, standard deviation 0.37 and the Spirulina group at 2.74, SD 0.45) After 21 weeks, the sneeze score of the placebo group was 1.91 (SD 0.52) and that of the Spirulina group was 0.58 (SD 0.50) (p<0.001). For nasal discharge, congestion and itching also documented similar results. If after 21 weeks in both groups occur improvements, may be due to the change of seasons or placebo effect. However, when directly comparing the data of the Spirulina group with the placebo group, they showed a large and steady improvement, which showed no symptoms until the end of the study. Perhaps the best and most interesting point in the study is the high level of satisfaction with the use of Spirulina versus the placebo group for treatment. At the end of the study, all the patients were asked to rate their state of symptoms on a scale of zero to ten with zero being no relief. The placebo group graded their experience at 3.54 (+/- 1.37) while the Spirulina group applauded with a 7.44 (+/- 0.89: p less than 0.001). In addition, the patients that took Spirulina rated their satisfaction as 7.21 (+/- 2.01), while the placebo group rated their experience as 3.54 (+/- 1.37) (p less than 0.001) [64]. As expressed by these researchers, Spirulina may be a “clinically effective” option for allergic rhinitis and is worthy of further study to investigate its mechanism.

EFFECTS AGAINST TOXICITIES FROM HEAVY METALS AND OTHER COMPOUNDS

Heavy metals such as cadmium, lead, mercury, copper, nickel and chromium are in the list of priority hazardous pollutants. Contact with heavy metals can cause neurological disorders, cellular aging, liver and kidney failure and carcinogenesis [66]. The liver is one of the organs affected by lead toxicity. On the other hand, the liver is one of the main organs for the storage and detoxification of poisoning with heavy metals [67]. In one study, the effect of spiroinema supplementation on lead-induced liver damage in rats was as follows. The activities of alanine transaminae (ALT) and aspartate transaminae (AST) are indicators of hepatotoxicity [68]. Lead toxicity significantly decreased at the level of the glutathione (GSH) and superoxide dismutase (SOD) and also significantly increased at malondialdehyde (MDA) and nitric oxide (NO) levels. Rats treated with spirulina supplementation showed a high level of GSH and produce SOD and a decrease in MDA and NO, indicating the antioxidant role of Spirulina. This may be due to the proposed role of GSH in the active excretion of lead by bile by binding to the thiol group of GSH, which is subsequently repelled. Reducing GSH levels can lead to oxidative stress and MDA increase [69,70]. Yaman et al. [71] in a trial with high mercury dosage in the mice, rising blood urea nitrogen (BUN) and serum creatinine, both of which are acute nephritis, increased 30% of Spirulina to their diet, resulting in a significant improvement in decrease BUN and serum creatinine levels. This was because of the presence of phycocyanine in the presence of Spirulina antioxidants. In recent years, some of its properties, such as protection against Arsenic toxicity, have been approved. While the added medicinal properties should be proven [72]. Also radiation protection by Spirulina can be attributed to phytopigments that include carotenoids, chlorophyll and phycocyanin [73].

CONCLUSION

Spirulina products buildup both the humoral and cellular of the immune system and possess anti-allergic properties by inducing IgA antibody and phycocyanin and decrease of IL4 inhibit release of histamine and functions as anti-inflammatory compound. Furthermore, Spirulina improves oxidative stress markers and NK activity in healthy subjects and CD4+ count in HIV+ patients. Previous studies indicate that some antioxidant and immunological markers are sensitive to stimuli that affect the mood of the individual. In this context different species of Spirulina, possibly having different biological effects, showed different suitability. Therefore, the study of the relationship between liking and markers of antioxidant and immune status should be measured in human’s studies. As a final point, clearly this safe food makes available nutritional support for optimum health and the multifunctional role of Spirulina in ideal natural drug with immense therapeutic properties.

1.       Cao G, Prior RL (1998) Comparison of different analytical methods for assessing total antioxidant capacity of human serum. Clin Chem 44: 1309-1315.

2.       Khan Z, Bhadouria P, Bisen P (2005) Nutritional and therapeutic potential of Spirulina. Curr Pharm Biotechnol 6: 373-379.

3.       Deng R, Chow TJ (2010) Hypolipidemic, antioxidant and anti-inflammatory activities of microalgae Spirulina. Cardiovasc Ther 28: e33-345.

4.       Belay A, Kato T, Ota Y (1996) Spirulina (Arthrospira): Potential application as an animal feed supplement. J Appl Phycol 8: 303-311.

5.       Fazilati M, Asghari A, Latifi AM, Salavati H, Choopani A (2016) Antioxidant properties of Spirulina. J Appl Biotechnol Rep 3: 345-351.

6.       Hasler CM (2002) Functional foods: Benefits, concerns and challenges - A position paper from the American Council on Science and Health. J Nutr 132: 3772-3781.

7.       Bhavisha R, Parula P (2010) Spirulina: Potential clinical therapeutic application. J Pharm Res 3: 1726-1732.

8.       Joventino IP, Alves HG, Neves LC, Pinheiro-Joventino F, Leal LK, et al. (2012) The microalga Spirulina platensis presents anti-inflammatory action as well as hypoglycemic and hypolipidemic properties in diabetic rats. J Complement Integr Med 9: 17.

9.       Cheng-Wu Z, Chao-Tsi T, Yuan-Zhen Z (1994) The effects of polysaccharide and phycocyanin from Spirulina platensis on peripheral blood and hematopoietic system of bone marrow in mice. In: Book of Abstracts. Second Asia Pacific Conference on Algal Biotechol 58.

10.    Thengodkar RRM, Sivakami S (2010) Degradation of chlorpyrifos by an alkaline phosphatase from the cyanobacterium Spirulina platensis. Biodegradation 21: 637-644.

11.    Jiménez C, Cossio BR, Labella D, Niell, FX (2003) The feasibility of industrial production of Spirulina (Arthrospira) in Southern Spain. Aquaculture 217: 179-190.

12.    Machu L, Misurcova L, Ambrozova JV, Orsavova J, Mlcek J, et al. (2015) Phenolic content and antioxidant capacity in algal food products. Molecules 20: 1118-1133.

13.    Jensen GS, Attridge VL, Beaman JL, Guthrie J, Ehmann A, et al. (2015) Antioxidant and anti-inflammatory properties of an aqueous cyanophyta extract derived from Arthrospira platensis: Contribution to bioactivities by the non-phycocyanin aqueous fraction. J Med Food 18: 535-541.

14.    Riss J, Décordé K, Sutra T, Delage M, Baccou JC, et al. (2017) 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: 7962-7967.

15.    Savranoglu S, Tumer TB (2013) Inhibitory effects of Spirulina platensis on carcinogen-activating cytochrome P450 isozymes and potential for drug interactions. Int J Toxicol 32: 376-384.

16.    Serban MC, Sahebkar A, Dragan S, Stoichescu-Hogea G, Ursoniu S, et al. (2016) A systematic review and meta-analysis of the impact of Spirulina supplementation on plasma lipid concentrations. Clin Nutr 35: 842-851.

17.    Vonshak A (1977) Spirulina platensis arthrospira: Physiology, cell-biology and biotechnology. CRC Press.

18.    Ismail M, Hossain MF, Tanu AR, Shekhar HU (2015) Effect of Spirulina intervention on oxidative stress, antioxidant status and lipid profile in chronic obstructive pulmonary disease patients. BioMed Res Int 2015: 486120.

19.    Parages ML, Rico R, Diaz RA, Chabrillon M, Sotiroudis T, et al. (2012) Acidic polysaccharides of Arthrospira (Spirulina) platensis induce the synthesis of TNF-α in RAW macrophages. J Appl Phycol 24: 1537-1546.

20.    Alam MA, Haider N, Ahmed S, Alam MT, Azeez A, et al. (2013) Tahlab (Spirulina) and few other medicinal plants having anti-oxidant and immunomodulatory properties described in Unani medicine - A review. Int J Pharm Sci Res 4: 4158.

21.    Henrikson R (1989) Earth food Spirulina. Laguna Beach, CA: Ronore Enterprises, Inc., p: 187.

22.    Habib MAB, Hungtington TC, Hasan MR (2008) A review on culture, production and use of Spirulina as food for humans and feeds for domestic animals and fish. Food and Agriculture Organization of the United Nations.

23.    Belay A (2002) The potential application of Spirulina (Arthrospira) as a nutritional and therapeutic supplement in health management. J Am Nutr Assoc 5: 27-48.

24.    Ghaeni M (2009) The effect of spirulina (fresh and dry) on some biological factors in Penaeus semisulcatus larvae. Islamic Azad University, Science and Research Branch, Tehran, p: 106.

25.    Choonawala BB (2007) Spirulina production in brine effluent from cooling towers.

26.    Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, et al. (2007) Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 39: 44-84.

27.    Olivero-David R, Schultz-Moreira A, Vázquez-Velasco M, González-Torres L, Bastida S, et al. (2011) Effects of Nori-and Wakame-enriched meats with or without supplementary cholesterol on aryl esterase activity, lipemia and lipoproteinemia in growing Wistar rats. Br J Nutr 106: 1476-1486.

28.    Sikder K, Kesh SB, Das N, Manna K, Dey S (2014) The high antioxidative power of quercetin (aglycone flavonoid) and its glycone (rutin) avert high cholesterol diet induced hepatotoxicity and inflammation in Swiss albino mice. Food Funct 5: 1294-1303.

29.    Wu WT, Chen HL (2011) Konjac glucomannan and inulin systematically modulate antioxidant defense in rats fed a high-fat fiber-free diet. J Agric Food Chem 59: 9194-9200.

30.    Sikder K, Das N, Kesh SB, Dey S (2014) Quercetin and β-sitosterol prevent high fat diet induced dyslipidemia and hepatotoxicity in Swiss albino mice. Indian J Exp Biol 52: 60-66.

31.    Banji D, Banji OJ, Pratusha NG, Annamalai AR (2013) Investigation on the role of Spirulina platensis in ameliorating behavioral changes, thyroid dysfunction and oxidative stress in offspring of pregnant rats exposed to fluoride. Food Chem 140: 321-331.

32.    Tang Y (2014) Extraction of polysaccharides from Spirulina with boiling water. Agric Sci Technol 15: 1043.

33.    Balachandran P, Pugh ND, Ma G, Pasco DS (2006) Toll-like receptor 2-dependent activation of monocytes by Spirulina polysaccharide and its immune enhancing action in mice. Int Immunopharmacol 6: 1808-1814.

34.    Abdel-Daim M, El-Bialy BE, Rahman HG, Radi AM, Hefny HA, et al. (2016) Antagonistic effects of Spirulina platensis against sub-acute deltamethrin toxicity in mice: Biochemical and histopathological studies. Biomed Pharmacother 77: 79-85.

35.    Hoseini S, Khosravi-Darani K, Mozafari M (2013) Nutritional and medical applications of Spirulina microalgae. Med Chem 13: 1231-1237.

36.    Bhat VB, Madyastha KM (2001) Scavenging of peroxynitrite by phycocyanin from Spirulina platensis: Protection against oxidative damage to DNA. Biochem Biophys Res Commun 275: 20-25.

37.    Subhashini J, Mahipal SV, Reddy MC, Mallikarjuna Reddy M, Rachamallu A, et al. (2004) Molecular mechanisms in C-Phycocyanin induced apoptosis in human chronic myeloid leukemia cell line-K562. Biochem Pharmacol 68: 453-462.

38.    Borowitzka MALJ (1988) Micro-algal biotechnology. Cambridge University Press.

39.    Boshra H, Li J, Sunyer JO (2006) Recent advances on the complement system of teleost fish. Fish Shellfish Immunol 20: 239-262.

40.    Mauri I, Romero A, Acerete L, Mackenzie S, Roher N, et al. (2011) Changes in complement responses in Gilthead seabream (Sparus aurata) and European seabass (Dicentrarchus labrax) under crowding stress, plus viral and bacterial challenges. Fish Shellfish Immunol 30: 182-188.

41.    Yano T (1992) Assays of hemolytic complement activity. Tech Fish Immunol 1992: 131-141.

42.    Hoskinson C, Chew B, Wong T (1990) Age-related changes in mitogen-induced lymphocyte proliferation and polymorphonuclear neutrophil function in the piglet. J Anim Sci 68: 2471-2478.

43.    Sylvester RJ, Meijden AP, Witjes JA, Kurth K (2005) Bacillus calmette-guerin versus chemotherapy for the intravesical treatment of patients with carcinoma in situ of the bladder: A meta-analysis of the published results of randomized clinical trials. J Urol 174: 86-91.

44.    He D, Li H, Yusuf N, Craig AE, Jun LI, et al. (2010) IL-17 promotes tumor development through the induction of tumor promoting microenvironments at tumor sites and myeloid-derived suppressor cells. J Immunol 184: 2281-2288.

45.    Wang L, Yi T, Kortylewski M, Pardoll DM, Zeng D, et al. (2009) IL-17 can promote tumor growth through an IL-6–Stat3 signaling pathway. J Exp Med 206: 1457-1464.

46.    Ollinger R, Kogler P, Troppmair J, Hermann M, Wurm M, et al. (2007) Bilirubin inhibits tumor cell growth via activation of ERK. Cell Cycle 6: 3078-3085.

47.    Nazarewicz RR., Dikalova A, Bikineyeva A, Ivanov S, Kirilyuk IA, et al. (2013) Does scavenging of mitochondrial superoxide attenuate cancer prosurvival signaling pathways? 19: 344-349.

48.    Regunathan C, Wesley S (2006) Pigment deficiency correction in shrimp broodstock using Spirulina as a carotenoid source. Aquacult Nutr 12: 425-432.

49.    Zhang H, Lin AP, Sun Y, Deng YM (2001) Chemo-and radio-protective effects of polysaccharide of Spirulina platensis on hemopoietic system of mice and dogs. Acta Pharmacologica Sinica 22: 1121-1124.

50.    Pardhasaradhi BV, Ali AM, Kumari AL, Reddanna P, Khar A (2003) Phycocyanin-mediated apoptosis in AK-5 tumor cells involves down-regulation of Bcl-2 and generation of ROS. Mol Cancer Ther 2: 1165-1170.

51.    Subhashini J, Mahipal SV, Reddy MC, Mallikarjuna RM, Rachamallu A, et al. (2004) Molecular mechanisms in C-phycocyanin induced apoptosis in human chronic myeloid leukemia cell line-K562. Biochem Pharmacol 68: 453-462.

52.    Qing, Z, Zhongmai H, Jiang-Jun H, Li-Min P, Ying Y (2011) Controlling the organic contamination strength of municipal wastewater with Spirulina platensis. In: Materials for Renewable Energy & Environment (ICMREE).

53.    Hernández CA, Nieves I, Meckes M, Chamorro G, Barron BL (2002) Antiviral activity of Spirulina maxima against herpes simplex virus type 2. Antiviral Res 56: 279-285.

54.    Hayashi K, Hayashi T, Kojima I (1996) A natural sulfated polysaccharide, calcium spirulan, isolated from Spirulina platensis: In vitro and ex vivo evaluation of anti-herpes simplex virus and anti-human immunodeficiency virus activities. AIDS Res Hum Retroviruses 12: 1463-1471.

55.    Hayashi T, Hayashi K, Maeda M, Kojima I (1996) Calcium spirulan, an inhibitor of enveloped virus replication, from a blue-green alga Spirulina platensis. J Nat Prod 59: 83-87.

56.    Luescher MM (2003) Algae, a possible source for new drugs in the treatment of HIV and other viral diseases. Curr Med Chem Anti-Infect Agents 2: 219-225.

57.    Simporec J, Zongo F, Ouattara Y, Kabore F, Dansou D, Bere A, et al. (2005) Nutrition rehabilitation of undernourished children utilizing Spiruline and Misola. Nutr J Biol Sci 49: 373-380.

58.    Teas J, Irhimeh M (2012) Wachters' Nutritional Programs. J Appl Phycol 24.

59.    Simpore J, Zongo F, Kabore F, Dansou D, Bere A, et al.(2005) Nutrition rehabilitation of HIV-infected and HIV-negative undernourished children utilizing Spirulina. Ann Nutr Metab 49: 373-380.

60.    Yang HZ, Lee EH, Kim HM (1997) Spirulina platensis inhibits anaphylactic reaction. Life Sci 61: 1237-1244.

61.    Kim HM, Lee EH, Cho HH, Moon YH (1998) Inhibitory effect of mast cell-mediated immediate-type allergic reactions in rats by Spirulina. Biochem Pharmacol 55: 1071-1076.

62.    Mao Tk, Water JVD, Gershwin ME (2005) Effects of a Spirulina-based dietary supplement on cytokine production from allergic rhinitis patients. J Med Food 8: 27-30.

63.    Ishii K (1999) Influence of dietary Spirulina platensis on IgA level in human saliva. J Kagawa Nutr Univ 30: 27-33.

64.    Cingi C, Conk-Dalay M, Cakli H, Bal C (2008) The effects of Spirulina on allergic rhinitis. Eur Arch Oto-Rhino-Laryngol 265: 1219-1223.

65.    Fedorov SN, Ermakova SP, Zvyagintseva TN, Stonik VA (2013) Anticancer and cancer preventive properties of marine polysaccharides: Some results and prospects. Mar Drugs 11: 4876-4901.

66.    Lefebvre DD, Edwards CD (2010) Decontaminating heavy metals using photosynthetic microbes. In: Shah V, editor. Emerging Environmental Technologies 2.

67.    Ohkawa H, Ohishi N, Yagi K (1979) Assay of lipid peroxide in animal tissue by thiobarbituric acid reaction. Ann Biochem 95: 351-358.

68.    Geraldine M, Venkatesh T (2009) Influence of minerals on lead-induced alterations in liver function in rats exposed to long-term lead exposure. J Hazard Mater 166: 1410-1414.

69.    Newairy, AS, Abdou HM (2009) Protective role of flax lignans against lead acetate induced oxidative damage and hyperlipidemia in rats. Food Chem Toxicol 47: 813-818.

70.    Reglero MM, Taggart MA, Monsalve-González L, Mateo R (2009) Heavy metal exposure in large game from a lead mining area: Effects on oxidative stress and fatty acid composition in liver. Environ Pollut 157: 1388-1395.

71.    Fukino H, Takagi Y, Yamane Y, (1990) Effect of Spirulina (S. platensis) on the renal toxicity induced by inorganic mercury and cisplatin (regular presentations). Proceedings of the 15^th Symposium on Environmental Pollutants and Toxicology. Eisei Kagaku 36: P5.

72.    Wu LC, Ho JA, Shieh MC, Lu IW (2005) Antioxidant and anti-proliferative activities of Spirulina and Chlorella water extracts. J Agric Food Chem 53: 4207-4212.

73.    Hirahashi T, Matsumoto M, Hazeki K, Saeki Y, Ui M, 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: 423-434.

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