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Abstract Title:

Phloretin suppresses thrombin-mediated leukocyte-platelet-endothelial interactions.

Abstract Source:

Mol Nutr Food Res. 2014 Apr ;58(4):698-708. Epub 2013 Dec 16. PMID: 24338998

Abstract Author(s):

Min Soo Kim, Sin-Hye Park, Seon-Young Han, Yun-Ho Kim, Eun-Jung Lee, Jung Han Yoon Park, Young-Hee Kang

Article Affiliation:

Min Soo Kim

Abstract:

SCOPE: Thrombin playing a pivotal role in coagulation cascade may influence the onset and progression of atherosclerosis as a pro-inflammatory mediator. This study investigated whether phloretin found in apple tree leaves, severed a linkage between thrombosis and atherosclerosis by thrombin.

METHODS AND RESULTS: Human endothelial cells were pre-treated with 1-20μM phloretin and stimulated with 10 U/mL thrombin. Phloretin attenuated adhesion of THP-1 monocytes and platelets to thrombin-inflamed endothelial cells with concurrent inhibition of protease-activated receptor (PAR-1) induction. The thrombin induction of endothelial CD40, endothelial integrin β3and P-selectin, and monocytic CD40L was dampened by phloretin. Additionally, phloretin inhibited monocyte secretion of MCP-1, IL-6 and IL-8 responsible for pro-inflammatory activity of thrombin inducing endothelial CD40. The monocyte COX-2 induction and PGE2 secretion due to thrombin were down-regulated by phloretin, deterring endothelial CD40 expression. Thrombin promoted production of PAI-1 and tissue factor in monocytes was attenuated by phloretin through blocking PAR-1 and CD40. Thrombin up-regulated the induction of endothelial connective tissue growth factor independent of PAR-1 activation, which was reversed by phloretin.

CONCLUSION: Phloretin disturbed tethering and stable adhesion of monocytes and platelets onto endothelium during increased thrombosis by thrombin. Phloretin would be a potent agent preventing thrombosis and atherosclerosis.

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