A novel protein C-phycocyanin plays a crucial role in the hypocholesterolemic action of Spirulina platensis concentrate in rats.

This study was designed to clarify the mechanisms of the hypocholesterolemic action of Spirulina platensis concentrate (SPC) and identify the novel hypocholesterolemic protein derived from SPC. We investigated the effects of casein or SPC on the solubility of cholesterol, taurocholate binding capacity in vitro, cholesterol absorption in Caco-2 cells, and cholesterol metabolism in rats for 10 d. We also evaluated the effects of SPC, C-phycocyanin (PHY), and PHY residue on cholesterol metabolism in rats fed a high-cholesterol diet for 5 d, and SPC or SPC-acetone extract for 10 d. SPC had a significantly greater bile acid-binding capacity than casein in vitro. Micellar cholesterol solubility and cholesterol uptake by Caco-2 cells was significantly lower in the presence of SPC compared with casein. Fecal excretion of cholesterol and bile acids was significantly greater in rats fed the SPC-supplemented diet than in those fed the casein control diet. Serum and liver cholesterol concentrations were significantly lower in rats fed SPC than in those fed casein. Thus, the hypocholesterolemic action of SPC may involve the inhibition of both jejunal cholesterol absorption and ileal bile acid reabsorption. Although no studies to date have found a hypocholesterolemic protein among the algal proteins, we report here the discovery of a hypocholesterolemic effect in the novel protein C-phycocyanin. This study provides the first direct evidence that PHY, a novel hypocholesterolemic protein derived from Spirulina platensis, can powerfully influence serum cholesterol concentrations and impart a stronger hypocholesterolemic activity than SPC in animals.

Phycocyanin enhances secretary IgA antibody response and suppresses allergic IgE antibody response in mice immunized with antigen-entrapped biodegradable microparticles.

In the present study, we have investigated the effects of phycocyanin, a biliprotein of Spirulina platensis, on mucosal and systemic immune responses and allergic inflammation in C3H/HeN and BALB/cA mice. To induce the antigen-specific antibodies in the peripheral lymphoid tissues such as Peyer's patches and mesenteric lymph nodes, biodegradable ovalbumin-entrapped poly (DL-lactide-co-glycolide) particles were used as an antigen. Two weeks after the onset of phycocyanin ingestion, mice were immunized with an aqueous ovalbumin (OVA) solution. Starting at one week after the primary immunization, the mice were subjected to oral immunization with the biodegradable OVA microparticles twice a week. IgA, IgE and IgG1 antibodies were determined by ELISA. The OVA microparticles of 4-microm diameter successfully induced antigen-specific antibodies. In the mice that received phycocyanin treatment for 6 wk, a marked increase in the antigen-specific, as well as the total, IgA antibody level was observed in the Peyer's patches, mesenteric lymph nodes and intestinal mucosa as well as in the spleen cells. Both antigen-specific IgG1 and IgE antibody levels in the serum were suppressed by ingestion of phycocyanin for 8 wk. However, inflammation of the small intestine, monitored as vascular permeability by the Evans blue-leaking method was reduced by phycocyanin at 6 wk, which preceded the suppression of antigen-specific IgG1 and IgE antibody production by 2 wk. These results suggest that phycocyanin enhances biological defense activity against infectious diseases through sustaining functions of the mucosal immune system and reduces allergic inflammation by the suppression of antigen-specific IgE antibody.

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.

Spirulina platensis is a cyanobacterial species that is surmised to potentiate the immune system leading to suppression of cancer development and viral infection. Here, we identified the molecular mechanism of the human immune potentiating capacity of Spirulina by analyzing blood cells of volunteers with pre and post oral administration of hot water extract of Spirulina. NK functions represented by IFN gamma production and cytolysis were enhanced after administration of Spirulina in >50% subjects. IFN gamma was produced in an IL-12/IL-18-dependent fashion. In vitro stimulation of blood cells with BCG cell wall skeleton (CWS) allowed more potent IL-12 p40 production in cells from volunteers given Spirulina than in cells without pre-exposure to Spirulina. As BCG-CWS serves as a ligand for Toll-like receptor (TLR) 2 and 4 to raise the maturation stage of monocytes/macrophages, Spirulina may be involved in the signaling responses through Toll in blood cells even when orally administered. These observations indicated that in humans Spirulina acts directly on myeloid lineages and either directly or indirectly on NK cells. The presence of co-operative IL-12 and IL-18 is critically important for NK-mediated IFN gamma production.