TNF-α and IL-6 inhibitory effects of cyclic dipeptides isolated from marine bacteria Streptomyces sp

Inflammation is mediated by a variety of soluble factors, including a group of secreted polypeptides known as cytokines. The anti-inflammatory cytokines are a series of immune regulatory molecules that control the pro inflammatory cytokine response. Cytokines act in concert with specific cytokine inhibitors and soluble cytokine receptors to regulate the human immune response. The aim of the present study is to probe the anti-inflammatory potential of the crude extract and the bioactive metabolite isolated from marine bacteria Streptomyces sp. on key inflammatory mediators like tumor necrosis factor-alpha and interleukin-6. Here, we isolated ten known pyrazine-1,4-dione substituted cyclic dipeptide by semi-preparative HPLC and studied their anti-inflammatory activities against tumor necrosis factor-alpha and interleukin-6. Compound 3, 4, 5, 7 and 8 showed good inhibition of the both the cytokines in lipopolysaccharide-stimulated macrophages. The study reveal that compound 7 was to be specific inhibitor for tumor necrosis factor-alpha which efficiently inhibited tumor necrosis factor-alpha release in a dose-dependent manner and decreased lipopolysaccharide induced tumor necrosis factor-alpha production in human peripheral blood mononuclear cells in both the in vitro and in vivo experiments.