Naturally occurring benzophenones and xanthones from <i>Garcinia smeathmannii</i> (Planch. & Triana) Oliv. displayed anti-inflammatory effects by modulating the activities of inflammatory mediators in LPS-stimulated RAW 264.7 macrophages.

Abstract

<b>Introduction:</b> There is a growing interest in studying natural products for the identification of novel lead compounds for drug development for treating inflammatory diseases. Although some studies have focused anti-inflammatory activity of benzophenones and xanthones, exploring additional targets such as enzymes and cytokines, involved in their inflammatory response could provide more comprehensive understanding of the compounds' anti-inflammatory effects. In this study, four xanthones ananixanthone (<b>1</b>), smeathxanthone A (<b>2</b>), smeathxanthone B (<b>3</b>), and 1,3,5,8-tetrahydroxy-2-(3-methybut-2-enyl)-4-(3,7-dimethyloct-2,6-dienyl) xanthone (<b>4</b>); and three benzophenones guttiferone O (<b>5</b>), guttiferone M (<b>6</b>), and aristophenone A (<b>7</b>) from <i>Garcinia smeathmannii</i> (Planch. & Triana) Oliv. were investigated for their effect on nitric oxide production, cyclooxygenase, lipoxygenase inhibition, and Th1/Th2 cytokines production in activated RAW 264.7 macrophages. <b>Methods:</b> The Griess reagent method and the ferrous oxidation-xylenol orange assay were used to evaluate the inhibition of NO production and the 15-lipoxygenase activity respectively. Cyclooxygenase activity was assessed using the fluorometric COX activity assay kit and measurement of Th1/Th2 cytokines was performed using a flow cytometer. <b>Results:</b> All the tested compounds exhibited a dose-dependent inhibition of NO production with varying degrees of inhibitory effects on 15-LOX activity. Compound (<b>6</b>), displays the best inhibitory effect on COX-1/COX-2 activity. A general trend of the tested compounds on cytokines profiles revealed that compound (<b>5</b>) showed a pronounced enhancement of anti-inflammatory cytokines (IL-4 and IL-10). <b>Conclusion:</b> This observation supports future exploration of ananixanthone (<b>1</b>), guttiferone O (<b>5</b>), and guttiferone (<b>6</b>) as potential candidates for the development of anti-inflammatory drugs.