Ganodermycin, a novel inhibitor of CXCL10 expression from Ganoderma applanatum

Abstract

CXCL10 (inducible protein-10) is a highly inducible chemoattractant, which contributes to the recruitment of inflammatory cells, such as macrophages and T-lymphocytes, and thereby has important roles in chronic inflammatory conditions. In a search for new inhibitors of CXCL10 expression in MonoMac6 cells, a novel compound, designated as Ganodermycin, was isolated from fermentations of the basidiomycete Ganoderma applanatum. The structure was determined by a combination of spectroscopic techniques. Ganodermycin inhibited the lipopolysaccharide (LPS)/interferon (IFN)-γ-induced CXCL10 promoter activity in transiently transfected MonoMac6 cells in a dose-dependent manner with IC(50) values of 15-20 μg ml(-1) (53-71 μM). Ganodermycin also reduced LPS/IFN-γ-induced CXCL10 protein synthesis and excretion.