Inhibitory Effects of Fungal Bis(naphtho-γ-pyrone) Derivatives on Nitric Oxide Production by a Murine Macrophage-Like Cell Line, RAW 264.7, Activated by Lipopolysaccharide and Interferon-γ

Abstract

Inhibitory effects of six fungal bis(naphtho-γ-pyrone) derivatives on nitric oxide (NO) production by a murine macrophage-like cell line, RAW 264.7, which was activated by lipopolysaccharide and interferon-γ were examined. Among these derivatives, chaetochromin (4) (IC₅₀: 0.8 μM), cephalochromin (1) (IC₅₀ 1.5 μM), and dihydroisoustilaginoidin A (6) (IC₅₀ 2.8 μM) exhibited strong inhibitory activity. The bis(naphtho-γ-pyrone) derivatives did not affect the enzyme activity of inducible nitric oxide synthase (iNOS). However, these derivatives significantly reduced both the induction of iNOS protein and iNOS mRNA expression. These results suggest that the bis(naphtho-γ-pyrone) derivatives have the pharmacologic ability to suppress NO production by activated macrophages.