Protective Effects of Nobiletin Against Endotoxic Shock in Mice Through Inhibiting TNF-α, IL-6, and HMGB1 and Regulating NF-κB Pathway

Nobiletin (NOB), the major bioactive component of polymethoxyflavones in citrus fruits, has been reported possessing significant biological properties. The purpose of the present study was to investigate the protective role of NOB on lipopolysaccharide (LPS)-induced endotoxic shock in mice. We found pretreatment with NOB increases the survival rate of mice after endotoxin injection. The present study clearly demonstrates that pretreatment with NOB decreases the production of early pro-inflammatory cytokines TNF-α, IL-6, and late-phase mediator HMGB1 in serum and tissues of kidney, lung, and liver. The histopathological study indicates that NOB administration significantly attenuate tissues injury induced by LPS. Moreover, NOB suppresses the activity of nuclear factor-kappa B (NF-κB). These results suggest that NOB protects mice against LPS-induced endotoxic shock through inhibiting the production of TNF-α, IL-6, and HMGB1 and the activation of NF-κB, which elucidate that NOB may be a promising drug candidate for the treatment of septic shock.