Atrovirinone inhibits proinflammatory mediator synthesis through disruption of NF-κB nuclear translocation and MAPK phosphorylation in the murine monocytic macrophage RAW 264.7

Abstract 

In a previous communication we showed that atrovirinone, a 1,4-benzoquinone isolated from the roots of Garcinia atroviridis, was able to inhibit several major proinflammatory mediators of inflammation. In this report we show that atrovirinone inhibits NO and PGE₂ synthesis through inhibition of iNOS and COX-2 expression. We also show that atrovirinone inhibits the secretion of IL-1β and IL-6 in a dose dependent fashion whereas the secretion of IL-10, the anti-inflammatory cytokine, was enhanced. Subsequently we determined that the inhibition of proinflammatory cytokine synthesis and inducible enzyme expression was due to a dose-dependent inhibition of phosphorylation of p38 and ERK1/2. We also showed that atrovirinone prevented phosphorylation of I-κBα, which resulted in a reduction of p65NF-κB nuclear translocation as demonstrated by expression analysis. We conclude that atrovirinone is a potential anti-inflammatory drug lead that targets both the MAPK and NF-κB pathway.

Keywords: Atrovirinone, Garcinia atroviridis, iNOS, COX-2, Cytokines, MAPK, NF-κB

Abbreviations: NO, nitric oxide, PGE₂, prostaglandin E₂, iNOS, inducible nitric oxide synthase, COX-2, cyclooxygenase-2, NF-κB, nuclear factor-κB, I-κB, inhibitory-κB, IL, interleukin, MAPK, mitogen-activated protein kinase, ERK, extracellular-regulated kinase