Anti-inflammatory effect of veratric acid through regulating of PI3K/Akt pathway and histone acetylation

Abstract

Veratric acid, a simple benzoic acid, is known to exert several pharmacological effects including anti-oxidation, anti-inflammation and anti-hyperlipidemia. This study was focused on inhibitory effects of veratric acid on nitric oxide (NO) production in LPS-induced RAW264.7 cells. Veratric acid significantly suppressed mRNA and protein levels of iNOS resulting in the decrease of NO production in a dose-dependent manner. LPS-induced effects on PI3K subunits, including p85, p110α and p110β, and Akt were reduced by veratric acid. Also, veratric acid effectively decreased p300 acetylation and ATF-2 phosphorylation of what were consistently regulated by LY294002, a specific PI3K inhibitor. Moreover, LPS-induced HDAC3 expression and histone H4 acetylation were suppressed by veratric acid and LY294002. Our finding indicate that inhibitory effects of veratric acid on iNOS expression require regulation of PI3K/Akt signaling inducing recovery of the basal level of histone H4 acetylation through suppression LPS-induced HAT activity of p300 and ATF-2, and HDAC3 expression.