Anti-inflammatory effects of vicenin-2 and scolymoside on polyphosphate-mediated vascular inflammatory responses

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Abstract
Recent results indicate that polyphosphate (polyP) released by human endothelial cells can function as a pro-inflammatory mediator. Cyclopia subternata is a medicinal plant commonly used in traditional medicine to relieve pain in biological processes. This study was undertaken to investigate whether two structurally related active compounds found in C. subternata, namely vicenin-2 and scolymoside, can modulate polyP-mediated inflammatory responses in human umbilical vein endothelial cells (HUVECs) and in mice. The anti-inflammatory activities of vicenin-2 and scolymoside were determined by measuring permeability, leukocytes adhesion and migration, and activation of pro-inflammatory proteins in polyP-activated HUVECs and mice. In addition, the beneficial effects of vicenin-2 and scolymoside on survival rate in polyP-injected mice were determined. We found that vicenin-2 and scolymoside inhibits polyP-mediated barrier disruption, the expressions of cell adhesion molecules, and leukocyte to HUVEC adhesion/migration. Interestingly, polyP-induced NF-κB activation and the productions of TNF-α and IL-6 were inhibited by vicenin-2 and scolymoside in HUVECs. These anti-inflammatory functions of vicenin-2 and scolymoside were confirmed in polyP-injected mice. These results suggest that vicenin-2 and scolymoside have therapeutic potential for various systemic inflammatory diseases.

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