Anti-inflammatory effect of gamma-irradiated genistein through inhibition of NF-κB and MAPK signaling pathway in lipopolysaccharide-induced macrophages

Abstract

Genistein was irradiated with γ-irradiation at doses of 0, 10, 30, 50, 100, and 150 kGy. We observed that the decrease in the genistein peak after gamma irradiation was concomitant with the appearance of several new peaks. 150 kGy gamma-irradiated genistein did not exert cytotoxicity in macrophages, and inhibited inducible nitric oxide synthase-mediated nitric oxide production and pro-inflammatory cytokines level, such as tumor necrosis factor-α, interleukin-6 and interleukin-1β, in lipopolysaccharide (LPS)-induced macrophages. The treatment of LPS-stimulated macrophages with 150 kGy gamma-irradiated genistein resulted in a significant decrease in cyclooxygenase-2 levels, as well as the expression of cell surface molecules, such as CD80 and CD86. Furthermore, we also found that the anti-inflammatory action of 150 kGy gamma-irradiated genistein occurred through an inhibition of mitogen-activated protein kinases (extracellular signal-regulated kinase 1/2, p38 and c-Jun N-terminal kinase) and nuclear factor-κB signaling pathways based on a toll-like receptor 4 in macrophages, which may be speculated that several radiolysis products of genistein transformed by gamma-irradiation induce the inhibition of pro-inflammatory mediators. From these findings, it seems likely that gamma-irradiated genistein could play a potent role in the treatment of inflammatory disease as a value-added product in the medical industry.