Inhibition of lipopolysaccharide-induced inflammatory responses by 1 '-acetoxychavicol acetate

Lipopolysaccharide on gram negative bacteria can be detected by Toll-like receptor 4 (TLR4) to elicit a series of innate immune responses, leading to inflammation to eliminate the targeted pathogen. However, dysregulation in the responses results in excessive inflammation. The 1'-acetoxychavicol acetate (ACA) is a bioactive compound originated from Alpinia species known to have anti-inflammatory and apoptosis-inducing properties. Here, we found that ACA inhibits lipopolysaccharide-induced expression and production of proinflammatory cytokines such as interleukin 6 and TNF alpha by macrophages. ACA suppresses the activation of NF-kappa B and MAP kinases in TLR4 signaling. Moreover, ACA also inhibits TLR4-mediated induction of type I interferon by suppressing IRF3 activation. In lipopolysaccharide-challenged mice, ACA treatment successfully increased the survival of mice and alleviated inflammation in the lung. Thus, ACA is a potential anti-inflammatory agent to regulate excessive inflammation.