Whiskey congeners suppress LPS/IFNγ-induced NO production in murine macrophage RAW 264 cells by inducing heme oxygenase-1 expression.

Whiskey includes many nonvolatile substances (whiskey congeners; Whc) that seep from the oak cask during the maturation process. To date, many functions of Whc have reported, such as antiallergy and antimelanogenesis. This study examined the effect of Whc on LPS/IFNγ-induced nitric oxide (NO) production in murine macrophage RAW 264 cells. Whc suppressed LPS/IFNγ-induced NO production in a concentration-dependent manner. To determine the active compounds in Whc, the effect of 10 major compounds isolated from Whc on LPS/IFNγ-induced NO production was examined. Coniferylaldehyde (CA) and sinapylaldehyde (SiA) strongly suppressed LPS/IFNγ-induced NO production. Pretreatment with Whc, CA, and SiA induced heme oxygenase-1 (HO-1) expression. The expression of HO-1 by Whc, CA, and SiA pretreatment was due to activation of Nrf2/ARE signaling via the elevation of intracellular reactive oxygen species. To investigate the in vivo effects of Whc, Whc was administered to mice with antitype II collagen antibody-induced arthritis, and we the arthritis score and hind paw volume were measured. Administration of Whc remarkably suppressed the arthritis score and hind paw volume. Taken together, these findings suggest that Whc is beneficial for the treatment of inflammatory disease.