Kenichi Kosuna

Isoflavone aglycon produced by culture of soybean extracts with basidiomycetes and its anti-angiogenic activity

Soybean extracts (SBE) containing isoflavone glycosides were cultured with Ganoderma lucidum mycelia producing β-glucosidase. The anti-angiogenic effects of the cultivated product, containing rich in genistein, named GCP (genistein combined polysaccharide), were assessed with chick chorioallantoic membranes (CAM) and a mouse dorsal air-sac model. β-Glucosidase produced by the mycelia converted the isoflavone glycosides into aglycons. A test of volunteers showed that serum concentrations of genistein in the subjects treated with GCP (n=4) at 3 h after administration were significantly higher than those in the subjects treated with SBE (n=4). GCP inhibited angiogenesis in CAM, and the activity of GCP was greater than that of SBE. GCP inhibited the formation of new vessels induced by colon carcinoma cells in vivo.

Active hexose correlated compound enhances tumor surveillance through regulating both innate and adaptive immune responses

Active hexose correlated compound (AHCC) is a mixture of polysaccharides, amino acids, lipids and minerals derived from cocultured mycelia of several species of Basidiomycete mushrooms. AHCC has been implicated to modulate immune functions and plays a protective role against infection. However, the potential role of AHCC in tumor immune surveillance is unknown. In this study, C57BL/6 mice were orally administered AHCC or water, followed by tumor cell inoculation. We showed that compared to pure water-treated mice, AHCC treatment significantly delayed tumor development after inoculation of either melanoma cell line B16F0 or lymphoma cell line EL4. Treatment with AHCC enhanced both Ag-specific activation and proliferation of CD4+ and CD8+ T cells, increased the number of tumor Ag-specific CD8+ T cells, and more importantly, increased the frequency of tumor Ag-specific IFN-γ producing CD8+ T cells. Interestingly, AHCC treatment also showed increased cell number of NK and γδ T cells, indicating the role of AHCC in activating these innate-like lymphocytes. In summary, our results demonstrate that AHCC can enhance tumor immune surveillance through regulating both innate and adaptive immune responses.

Oral Administration of Active Hexose Correlated Compound Enhances Host Resistance to West Nile Encephalitis in Mice

West Nile virus (WNV) poses a serious threat to public health, especially to the elderly and the immuno-compromised. Neither vaccines nor treatments are available for humans. Active hexose correlated compound (AHCC) is an extract of Lentinula edodes of the Basidiomycete family of fungi rich in alpha-glucans. In this study, we evaluated the effect of AHCC on host susceptibility in the murine model of WNV infection. Mice orally administered with AHCC (600 mg/kg) every other day for 1 wk before and at d 1 and 3 postinfection were assessed using viremia levels, survival rate, and protective immunity. AHCC administration in young (6- to 8-wk-old) mice attenuated viremia and mortality following lethal WNV infection. WNV-specific IgM and IgG production and gammadelta T cell expansion were also enhanced in these mice. Aged (21- to 22-mo-old) mice were more susceptible to WNV infection than young mice, partially due to the dysfunction of gammadelta T cell subsets. AHCC administration in aged mice enhanced the protective Vgamma1(+) T cell response as well as WNV-specific IgG but not IgM antibodies production. AHCC administration in aged mice attenuated viremia levels but led to no difference in mortality rate. Overall, our data suggests that AHCC enhances protective host immune responses against WNV infection in young and aged mice. Dietary supplementation with AHCC may be potentially immunotherapeutic for WNV-susceptible populations.

Anti-allergy Activity of Perilla

Perilla was evaluated an anti-allergy activity in vitro and the clinical examination.TNF was used as the indicator.TNF, which is a kind of monokine produced by macrophage, shows the anti-tumor activity. The activity induced by TNF is well known as one of BRM (Biological Response Modifiers) mechanism, however, the excessive production of TNF causes unfavorable inflammation.Therefore, a suppressive activity of perilla on TNF production was examined.When the perilla extract was applied to mice, TNF production decreased one-third compard with the placibo.We added perilla extract to skin cream, and gave a clinical examination to allergodermia patients. The results were good for many of the patients.