Inhibitory effects of 2-amino-3H-phenoxazin-3-one on the melanogenesis of murine B16 melanoma cell line.

Hyperpigmentations are a serious concern addressed by both the medical community and the cosmetic industry through the development of agents that block melanin biosynthesis. In this study, we found that 2-amino-3H-phenoxazin-3-one (APO), isolated from extracts of the edible mushroom Agaricus bisporus Imbach, exhibited potent inhibitory effects on melanogenesis in B16 cells, a murine melanoma cell line. APO inhibited melanin biosynthesis at 1,000 times lower concentrations (IC(50)=1.

Creation of interferon-alpha8 mutants with amino acid substitutions against interferon-alpha receptor-2 binding sites using phage display system and evaluation of their biologic properties.

In this study, we describe the creation of three interferon-alpha (IFN-alpha)8 mutants with markedly higher antiviral and antiproliferative activities in comparison with those of the wild-type (wt)IFN-alpha8, wtIFN-alpha2, and IFN-con1 using a phage display system. Sequence analysis showed that three out of the six hot-spot amino acid residues of wtIFN-alpha8 known to be important for the interaction with the IFN-alpha receptor-2 (IFNAR-2)-binding sites were substituted to other amino acids and the others remained. Although affinity analysis revealed that the dissociation constant (K(D)) of IFN-alpha8 mutants was almost the same with that of wtIFN-alpha8, furthermore, the rates of association (k(a)) and dissociation (k(d)) were relatively lower.

Anti-inflammatory and immunomodulatory properties of 2-amino-3H-phenoxazin-3-one.

Accumulating evidence suggests that nitric oxide (NO) and prostaglandin E(2) (PGE(2)) are involved in the pathogenesis of various chronic inflammatory diseases and cancer. During the course of a screening program to identify natural anti-inflammatory substances, we isolated the compound 2-amino-3H-phenoxazin-3-one (APO) from an extract of the edible brown mushroom Agaricus bisporus IMBACH. APO inhibited NO production by mouse peritoneal macrophages in response to the pro-inflammatory stimuli lipopolysaccharide (LPS) and interferon (IFN)-gamma (LPS/IFN-gamma) at low concentrations (IC(50)=1.

Cotreatment with interferon-alpha and -gamma reduces liver fibrosis in a rat model.

Background/Aims: Interferon-alpha is used widely to treat viral hepatitis. Interferon-gamma modulates a system attacking infected cells and also has an anti-fibrotic effect. A treatment with interferon-alpha and -gamma has undergone trials in eliminating hepatitis C virus.

Interferon alfa down-regulates collagen gene transcription and suppresses experimental hepatic fibrosis in mice.

The equilibrium between the production and degradation of collagen is rigorously controlled by a number of growth factors and cytokines. Interferon alfa (IFN-alpha) is now widely used for the treatment of chronic hepatitis C, which can improve serum levels of fibrotic markers and the degree of hepatic fibrosis, not only in patients who responded to therapy but also in those in whom it is ineffective. These findings may suggest that IFN-alpha possesses direct antifibrotic effects in addition to its antiviral activity.

Antitumor activity of interleukin-18 against the murine T-cell leukemia/lymphoma EL-4 in syngeneic mice.

Interleukin (IL)-18 induces interferon (IFN)-gamma production by T cells and natural killer (NK) cells, and augments NK cell activity in mouse spleen cell cultures. It has recently been demonstrated that in vivo administration of IL-18 to mice results in considerable antitumor effects against syngeneic Meth A sarcoma. In this study, the antitumor effects of IL-18 against murine T-cell leukemia (EL-4) were evaluated.