Ferulaldehyde, a Water-Soluble Degradation Product of Polyphenols, Inhibits the Lipopolysaccharide-Induced Inflammatory Response in Mice

Antiinflammatory properties of polyphenols in natural products, traditional medicines, and healthy foods were recently attributed to highly soluble metabolites produced by the microflora of the intestines rather than the polyphenols themselves. To provide experimental basis for this hypothesis, we measured antiinflammatory properties of ferulaldehyde (FA), a natural intermediate of polyphenol metabolism of intestinal microflora, in a murine lipopolysaccharide (LPS)-induced septic shock model. We found that intraperitoneally administered FA (6 mg/kg) prolonged the lifespan of LPS-treated (40 mg/kg) mice, decreased the inflammatory response detected by T₂-weighted in vivo MRI, decreased early proinflammatory cytokines such as tumor necrosis factor-α and interleukin (IL)-1β, and increased the antiinflammatory IL-10 in the sera of the mice. Additionally, FA inhibited LPS-induced activation of nuclear factor κB transcription factor in the liver of the mice. According to our data, these effects were probably due to attenuating LPS-induced activation of c-Jun N-terminal kinase and Akt. Furthermore, FA decreased free radical and nitrite production in LPS plus interferon-γ-treated primary mouse hepatocytes, whose effects are expected to contribute to its antiinflammatory property. These data provide direct in vivo evidence, that a water-soluble degradation product of polyphenols could be responsible for, or at least could significantly contribute to, the beneficial antiinflammatory effects of polyphenol-containing healthy foods, natural products, and traditional medicines.