Gamma irradiation enhanced Tollip-mediated anti-inflammatory action through structural modification of quercetin in lipopolysaccharide-stimulated macrophages.

The changes in molecular structure and anti-inflammatory action of a gamma-irradiated quercetin were examined. Quercetin was gamma-irradiated at doses of 0, 15, 30, 50, 100 and 150kGy, which induced new radiolytic peaks (the highest radiolytic peak at a dose of 30kGy). Treatment of intact- and gamma-irradiated quercetin did not induce a significant cellular toxicity of macrophages at concentrations ranging from 12.5 to 50μM. Treatment of LPS-stimulated macrophages with gamma-irradiated quercetin (30kGy) showed a higher inhibitory action than intact-quercetin groups in the excessive expression of inducible nitric oxide synthases-mediated nitric oxide, prostaglandin E2, pro-inflammatory cytokines level, such as tumor necrosis factor-α, interleukin-6 and interleukin-1β, reactive oxygen species, as well as cell surface molecules (CD80, CD86, and MHC class I/II). The inhibition of LPS-stimulated pro-inflammatory mediators was mediated through a suppression of mitogen-activated protein kinases and nuclear factor-κB pathways. In addition, gamma-irradiated quercetin (30kGy) markedly elevated the expression of the Toll-interacting protein compared to intact-quercetin. The inhibitory action of intact- and gamma-irradiated quercetin on the production of IL-6 and TNF-α was not observed in the down-regulation of Tollip. Therefore, these findings represent new insights into the understanding of the changes in molecular structure and the physiological properties of natural products through the application of radiation technology.