Parthenolide, an anti-inflammatory NFκB inhibitor, stimulates platelet production and blunts platelet activation (87.17)

Abstract

Abstract Platelets play a significant role in hemostasis, and are critically involved in common medical complications including thrombocytopenia, ischemia, and atherosclerosis. Platelets can also directly induce inflammation and influence immune cells by releasing inflammatory mediators such as CD40 Ligand, TGF-β, PGE2, IL-1β, and MIP-1α. Despite these recent findings, platelet signaling pathways remain unclear and are under current investigation. Recently, our lab identified the presence of NFκB transcription factors in platelets. Because platelets are anucleate, we hypothesize an alternative role for NFκB in platelet function. To further study the role of NFκB in platelets, we tested the effects of an NFκB inhibitor, Parthenolide, on human platelets and Meg-01 cells, a human megakaryoblastic cell line. Parthenolide is an extract of the Feverfew plant used in herbal therapies to dampen inflammation. We found that Parthenolide directly influenced human platelets by diminishing clot retraction and spreading. In addition, we found that Parthenolide increased platelet production, increased heme oxygenase-1 (up to 2000-fold), and increased glutathione levels over time (p=0.02) in Meg-01 cells. These data suggest that the anti-inflammatory properties of Parthenolide may be partially due to its ability to suppress platelet activation and up-regulate anti-oxidant pathways.