build up both the humoral and the cellular immune system (summarized in Figure 6.2). Sulfated-polysaccharides isolated from a water extract of Spirulina, called calcium-spirulan (Ca-Sp), exhibit immunomodulatory and antiviral activities.47-50 Furthermore, immolina, a high-molecular-weight polysaccharide fraction of Spirulina, promotes chemokine expression in human monocytic THP-1 cells.51 Other investigations have studied the use of the Spirulina in improving immune response.52-55 Polysaccharides and phycocyanin from Spirulina enhance bone marrow reproduction, thymus growth, and spleen cell proliferation, increasing immunity in the animal model, such as mice. Studies have also demonstrated that Spirulina up-regulates the immune system by improving their ability to function in spite of stress from environmental toxins, bacteria, and virus.47-51,53,54,56 The literature states that phycocyanin from Spirulina stimulates hematopoiesis, and especially erythropoiesis, by inducing the release of erythropoietin hormone (EPO).1 Phycocyanin and polysaccharides from Spirulina promote antibody and white blood cell production.53-56 According to Qureshi andAli (1996),53 the percentage of phagocytic macrophages in cats increased when they were administered a water-soluble extract of S. platensis. Moreover, the water-soluble extract of S. platensis caused the secretion of interleukins, such as IL-1, from murine peritoneal macrophages,55 and the proliferation of thymocytes. In addition, the effect of Spirulina on nonspecific immunity has been measured at the level of natural killer (NK) cell activity. Leukocytes taken from the spleen of chickens fed with Spirulina had greater antitumor cell activity than those of control animals, perhaps because of the production of such cytokines as interferon.54,57 Studies of a chicken model have demonstrated increased activity of NK cells in terminating tumor cells.53,54 The capacity of peritoneal macrophages to ingest latex particles has been evaluated in another study,55 in which peritoneal macrophages were removed from mice that had been fed on a Spirulina-supplemented diet (10% of the food by dry weight) for 10 weeks: a slight increase in the percentage of phagocytes from 91.3 to 95.9% was found in vitro. This work also found that phycocyanin of Spirulina inhibited release of histamine, a bioactive molecule involved with allergy.49,58
Soon after the discovery of the human immunodeficiency virus (HIV) as the causative agent of acquired immune deficiency syndrome (AIDS) in 1984, heparin and other sulfated polysaccharides were found to be potential inhibitors of HIV-1 replication in cell culture. As a potent anti-HIV drug candidate, sulfated polysaccharides had several promising advantages, including their ability to block HIV replication in cell culture at rather low concentrations (0.1-0.01 ^g/mL) without observable side-effects or cytotoxicity to the host cells at concentrations of up to 2.5 mg/mL. They could also inhibit the cytopathic effect of HIV, and prevent HIV-induced giant cell (syncytium) formation.59-63
As mentioned above, this important component of Spirulina, sulfated polysac-charides (calcium spirulan, Ca-SP) consists of rhamnose, ribose, mannose, fructose, galactose, xylose, glucose, glucuronic acid, galacturonic acid, sulfate, and calcium. Ca-SP inhibits the replication of various enveloped viruses, including herpes simplex virus, influenza virus, measles virus, mumps virus, and HIV,48,60,62,63 by selectively inhibiting the penetration of the virus into host cells. Its antiviral effect60 depends on the retention of its molecular conformation by chelating calcium ions with sulfate groups.60,62,63
In 1998, Ayehunie et al.59 investigated an aqueous extract of the blue-green algae, S. platensis, and found that it inhibited HIV-1 replication in human T-cell lines, peripheral blood mononuclear cells (PBMC), and Langerhans cells (LC). The 50% effective concentration (EC50) of the extract for reducing HIV-1 production in PBMCs ranged between 0.3 and 1.2 ^g/mL, while the 50% inhibitory concentration (IC50) of algae extract for PBMC growth ranged between 0.8 and 3.1 mg/mL. HIV-1 contagion was directly inactivated when the algae extract was preincubated with virus before it was added to human T-cell lines or other cells.
anticancer effects of spirulina
Spirulina is one of the richest natural sources of j-carotene and phycocyanin. Since both j -carotene and phycocyanin exhibit anticancer activity,64 Spirulina has also been claimed to be a potent cancer-fighting phytonutrient. Spirulina not only has antioxid-ant and immune-enhancing effects but also has anticancer properties that have been demonstrated in numerous studies of laboratory animals by preventing the development of experimentally produced cancers.57,65-68 The administration of phycocyanin to mice with liver cancer markedly increased their survival rate, perhaps because of the powerful antioxidant activity of phycocyanin, which prevented cancer and reduced DNA damage that is caused by free radicals. Subhashini et al. (2004)67 revealed that molecular mechanisms in C-phycocyanin induced apoptosis in human chronic myeloid leukemia cell line-K562. They observed a substantial decline (49%) in the proliferation of myeloid leukemia cell upon treatment with phycocyanin (50 ^M) for 48 h. C-Phycocyanin induced apoptosis in K562 cells by the following mechanism; (1) the release of cytochrome c from mitochondria into the cytosol, (2) the cleavage of poly(ADP-ribose) polymerase (PARP), and (3) the down regulation of Bcl-2. Phy-cocyanin induced apoptotic death in histiocytic tumor AK-5 cells, which process is inhibited by Bcl-2 expression through the regulation of the generation of free radicals. Phycocyanin, a natural product, may therefore be a chemotherapeutic agent based on its apoptotic activity against tumor cells.43
The hematopoietic function of Spirulina is very important to its anticancer effect, which increases the population of immune cells, and thereby immunoboosts natural resistance against cancer, and other diseases.53-55,68 Mishima et al. (1998)65 studied the inhibition of tumor invasion and metastasis by calcium spirulan (Ca-SP), a novel sulfated polysaccharide that is derived from Spirulina.68 Hirahashi et al. (2004)57 elucidated a possible mechanism by which Spirulina activates the human innate immune system. Spirulina promotes the production of interferon and tumor necrosis factor alpha (TNF-a) as well as NK cells when a hot water extract of S. platensis was orally administered. In other experimental animal studies, when extracts of Spirulina were injected directly into cancerous tumors, the tumor stopped growing.66 One human study involved individuals who had oral leukoplakia, a condition of the mouth that normally develops into cancer if it is untreated. The oral intake of Spirulina for 1 year prevented the progression of cancer in 45% of the study participants. More clinical investigations of humans must be conducted to verify the exact anticancer effects of Spirulina.
Apart from the positive effects of Spirulina on health discussed above (and summarized in Figure 6.3), Spirulina has potential neutraceutical and pharmaceutical characteristics, including hepatoprotective effects. Alcohol-medicated liver injury has been linked to oxidative stress that is caused by the production of ROI. Apoptotic cells can be observed in animal models with acute alcohol intoxication following glutathione depletion. Antioxidants reduce the rate of apoptosis in experimental animals.69,70 A study conducted by our group demonstrated that an aqueous extract of Spirulina significantly (p < .01) inhibits the proliferation of HepG2 and HSC, perhaps because of its antioxidative activity. The properties of Spirulina in Hepatic Protection are discussed below.
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