Aged red garlic extract suppresses nitric oxide production in lipopolysaccharide-treated RAW 264.7 macrophages through inhibition of NF-κB.

Lipopolysaccharides (LPS) activate nuclear factor kappa B (NF-κB), a transcription factor that is involved in inflammatory response. The pathways that activate NF-κB can be modulated by phytochemicals derived from garlic. We recently demonstrated that aged red garlic extract (ARGE), a new formulation of garlic, decreases nitric oxide (NO) generation by upregulating of heme oxygenase-1 (HO-1) in RAW 264.7 cells activated by LPS. However, the effects of ARGE on LPS-induced NF-κB activation are unknown. This study was performed to evaluate whether ARGE regulates LPS-induced NO production by modulation of NF-κB activation in macrophages. The inhibition of NF-κB by Bay 11-7085, an inhibitor of NF-κB, decreased LPS-induced NO production. ARGE treatment markedly reduced LPS-induced NO production and NF-κB nuclear translocation. ARGE downregulated expression of inducible nitric oxide synthase (iNOS) and upregulated expression of HO-1, a cytoprotective and anti-inflammatory protein. However, Bay 11-7085 only reduced iNOS expression. The NO production and iNOS expressions upregulated by suppression of HO-1 were suppressed by treatment with ARGE and Bay 11-7085. These results show that ARGE reduces LPS-induced NO production in macrophages through inhibition of NF-κB nuclear translocation and HO-1 activation. Compared to Bay 11-7085, ARGE may enhance anti-inflammatory effects by controlling other anti-inflammatory signals as well as regulation of NF-κB.