Veratric acid Induces p38-dependent Regulation of iNOS Expression in RAW264.7 cells
Veratric aicd is a phenolic compound, which is derived from medicinal mushrooms. In our study, veratric acid showed the effect on the reduction of nitric oxide (NO) production in LPS-stimulated RAW264.7 cells. The negative regulation of NO production in LPS-induced RAW264.7 cells were caused by the modulation of iNOS at mRNA and protein levels. The transcription factors for iNOS expression, including NF-κB, STAT-1, c-Jun, ATF-2, and Elk-1, were down-regulated by veratric acid. Because c-Jun, ATF-2, and Elk-1 is induced by p38, we determined that the effect of veratric acid on p38 expression, which was inactivated. Additionally, Akt and p110β, the catalytic subunit of PI3K, were inactivated by veratric acid. In the inhibition of p38 and PI3K, the inhibition of p38 did not modulate the expression of iNOS, the inhibition of PI3K, although, induced the synergic effect on the reduction of NO production. The results indicated veratric acid required p38 to regulate the expression of iNOS in LPS-stimulated RAW264.7 cells.