Inhibitory effect of 2′-hydroxycinnamaldehyde on nitric oxide production through inhibition of NF-κB activation in RAW 264.7 cells

Abstract

Cinnamomum cassia has been widely used for treating dyspepsia, gastritis, and inflammatory disease. In the present study, several of cinnamaldehyde derivatives were synthesized from various cinnamic acid based on the 2′-hydroxycinnamaldehyde isolated from the bark C. cassia Blume was investigated to compare their NO production and NF-κB activity from Raw 264.7 cell since nitric oxide (NO) and NF-κB have been shown to be implicated factors in the inflammatory disease. The results show that HCA, among the derivatives, most significantly inhibited lipopolysaccharide (LPS)-induced NO production and NF-κB transcriptional activity in a dose-dependent manner with an IC50 value of 8 and 22 μM, respectively. We next investigated putative possible mechanisms of inhibitory effect of HCA on NO production. The inhibition of NO by HCA was consistent with the inhibitory effect on LPS-induced inducible nitric oxide synthase (iNOS) expression. Moreover, HCA inhibited LPS-induced p50 and p65 translocation resulting in the inhibition of the DNA binding activity of the NF-κB, a central regulator of iNOS. The present results provided evidence that HCA, among cinnamaledhyde derivatives, has the most inhibitory effect on NO production through inhibition of NF-κB activation, and thus can be used as an anti-inflammatory agent.