Research: SAHLER and COLLEAGUES,

Listed in Issue 207

Abstract

SAHLER and COLLEAGUES, Department of Microbiology and Immunology, University of Rochester, Rochester, NY, USA investigated the effect of the feverfew plant-derived compound, parthenolide on platelet production and platelet activation due to its well-studied ability to induce apoptosis or differentiation in some types of cancer.

Background

Few treatments are available that can safely and effectively stimulate new platelet production for thrombocytopenic patients. Additionally, recipients of transfused platelets may experience an inflammatory response due to stored platelets becoming unnecessarily activated, thus creating the need for suitable agents that will dampen undesirable platelet activation. We investigated the effect of the feverfew plant-derived compound, parthenolide on platelet production and platelet activation because of its well-studied ability to induce apoptosis or differentiation in some types of cancer.

Methodology

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-kappaB 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.

Results

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-kappaB 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.

Conclusion

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

References

Sahler J, Bernard JJ, Spinelli SL, Blumberg N and Phipps RP. The Feverfew plant-derived compound, parthenolide enhances platelet production and attenuates platelet activation through NF-kappaB inhibition. Source Thrombosis Research. 127(5):426-34, 2011 May. Other ID Source: NLM. NIHMS262030 [Available on 05/01/12] Source: NLM. PMC3081947 [Available on 05/01/12]

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