The Feverfew plant-derived compound, parthenolide enhances platelet production and attenuates platelet activation through NF-κB inhibition

Overall, these data reveal that parthenolide has strong potential as a candidate to enhance platelet production and to dampen undesirable platelet activation.

Parthenolide was used to treat human megakaryoblastic cell lines, primary human and mouse megakaryocytes. Resulting platelet production and function was measured via flow cytometry. The two most common parthenolide signaling mechanisms, oxidative stress and nuclear factor-κB inhibition, were assessed within the megakaryocytes using reactive oxygen species, glutathione and luciferase reporter assays. The influence of parthenolide on ex vivo platelet activation was tested with parthenolide pretreatment followed by collagen or thrombin activation. The resulting P-selectin surface expression and released soluble CD40 ligand was measured.

Parthenolide stimulates functional platelet production from human megakaryocyte cell lines, and from primary mouse and human megakaryocytes in vitro. Parthenolide enhances platelet production via inhibition of nuclear factor-κB signaling in megakaryocytes and is independent of the parthenolide-induced oxidative stress response. Additionally, parthenolide treatment of human peripheral blood platelets attenuated activation of stimulated platelets.