Trilobatin attenuates the LPS-mediated inflammatory response by suppressing the NF-κB signaling pathway

We investigated the anti-inflammatory effect of trilobatin, the flavonoid isolated from the leaves of Lithocorpus polystachyus Rehd, as well as the underlying molecular mechanisms. Treatment with trilobatin (0.005-5 mu M) dose-dependently inhibited the lipopolysaccharide (LPS)-induced mRNA expression and secretion of pro-inflammatory cytokines, including tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6), in RAW 264.7 macrophages. However, no further inhibition was detected when the concentration of trilobatin was increased to 50 mu M. Western blot analysis confirmed that the mechanism of the anti-inflammatory effect was correlated with the inhibition of LPS-induced inhibitor of nuclear factor-kappa B alpha (I kappa B alpha) degradation and nuclear factor-kappa B (NF-kappa B) p65 phosphorylation. In addition, trilobatin also showed a significant inhibition of LPS-induced TNF alpha and IL-6 at both the mRNA and protein levels in a mouse model. Our results suggest that trilobatin potentially inhibits the LPS-induced inflammatory response by suppressing the NF-kappa B signaling pathway. (C) 2014 Elsevier Ltd. All rights reserved.