ANTI-INFLAMMATORY AND ANTIARTHRITICS PROPERTIES BY COMPONENTS OF FLONAT FAST® IN HUMAN MONOCYTES: NEW INSIGHTS FOR THE TREATMENT OF OSTEOARTHRITIS

Osteoarthritis (OA) is a degenerative joint disease sustained by inflammatory and oxidative signalling pathways and overproduction of cytokines that stimulate the release of matrix metalloproteinases (MMPs) that have degradative effects on the extracellular matrix. Within this pathogenic framework, monocyte/ macrophage-derived inflammatory cytokines contribute to amplify inflammation of OA synovial tissues. Most pharmacological approaches clinically used in OA treatment are effective in reducing pain and inflammation, but are not able to counteract the progression of disease and halt its onset. On this background purpose of this study was to investigate the anti-arthritic effects of the Flonat Fast® (FF), a commercial multi-component supplement composed by devil's claw, Boswelia serrata, Curcuma longa, Aesculus hippocastanum and bromelain, on inflamed human monocytes. THP-1 monocytes were treated with each Flonat Fast® components alone and in combination, for 4h before to be challenged with tumor necrosis factor(TNF)-?. The expression of several chemokines and cytokines including interleukin(IL)-6, IL-8, as well as the expression of cyclooxygenase(COX)-2 and MMP- 9 was tested at messenger and protein levels. The interference with the reactive oxygen species(ROS) production was evaluated by DCF-DA. Finally, endothelial monocyte adhesion assays were performed to assess the reduction in adhesion potential of THP-1. Under pro-inflammatory monocytes increased the expression of several pro-inflammatory genes. Pretreatment with each FF components, although with different strengths, significantly reverted the TNF-?-induced expression of COX-2, IL-6 and IL-8. Under the same pro-inflammatory conditions, the combined treatment with all FF components enhanced the anti-inflammatory activity and further down-regulated the pro-inflammatory gene expressions and the release of ROS. These effects functionally associated with a clear downregulation of the adhesion of monocytes to inflamed endothelium. Our findings suggest that FF components curb the pro-inflammatory activities of human monocytes. Being monocytes key actors in OA pathogenesis these effects confirm for FF anti-arthritic potentialities. In particular the combination of devil's claw, boswelia, curcuma, together to hippocastanum and bromelain could potentiate the respective mechanism of actions and significantly affect the pro-inflammatory stigmate of OA.