Diarylheptanoids with in vitro inducible nitric oxide synthesis inhibitory activity from Alnus hirsuta

Four diarylheptanoids were isolated from the leaf of Alnus hirsuta (Betulaceae) and have been assessed for nitric oxide (NO) production inhibitory effects in vitro. Oregonin (1) and hirsutanonol (2) were found to be potent inducible nitric oxide synthase (iNOS) inhibitors. Compounds 1 and 2 showed inhibition of NO synthesis in dose-dependent manners by murine macrophage-like RAW 264.7 cells stimulated with interferon-gamma (IFN-gamma) plus lipopolysaccharide (LPS). Their 50% inhibitory concentrations (IC50) were 3.8 and 14.3 microM, respectively. The inhibitory effects of these compounds on NO synthesis were due to suppression of iNOS mRNA expression as determined by Northern blotting.