Abstract
Allium macrostemon saponin is a traditional Chinese medicine that exhibits anti-atherosclerosis effects. However, the mechanism of its action has not been fully clarified. Platelet activation induced by CD40L plays an important role in the process of atherosis. In the present study, we demonstrate for the first time that A. macrostemon saponin inhibits platelet activation induced by CD40L. Moreover, the effects of saponin on platelet activation were achieved by activation of the classical CD40L-associated pathway, including the PI3K/Akt, MAPK and NF-κB proteins. In addition, the present study further demonstrated that saponin exhibited an effect on the TRAF2-mediated ubiquitination degradation, which contributed to the inhibition of the CD40 pathway and its downstream members. The findings determine that A. macrostemon saponin inhibits activation of platelets via activation of downstream proteins of the CD40 pathway. This in turn affected TRAF2-associated ubiquitination degradation and caused an anti-thrombotic effect.
Highlights
Atherosclerotic cardiovascular disease is the leading cause of death and morbidity worldwide and more than 80% of CVD mortality cases occur in developing countries according to a previous study (Steg et al, 2011)
The results from three volunteers were examined and the results indicated that the platelet activity markers CD62P and CD63 were inhibited by saponin treatment, following activation of the platelets by CD40L resulting in the upregulation of platelet active marker expression
In order to further verify the inhibition of platelet activation by saponin, we examined whether saponin could affect the release of TXB2 and plateletderived microvesicles (PMVs)
Summary
Atherosclerotic cardiovascular disease is the leading cause of death and morbidity worldwide and more than 80% of CVD mortality cases occur in developing countries according to a previous study (Steg et al, 2011). Atherosclerosis is the pathological basis of CVD and is considered a chronic inflammatory disease caused by complex immune and metabolic processes, in which platelet activation plays an important role. CD40 is a member of the tumor necrosis factor receptor (TNF-R) super family and binds to the CD40L, a 39KD transmembrane glycoprotein, which is biologically active (Lievens et al, 2009). During the process of platelet activation, the CD40L/CD40 pathway induces inflammation directly resulting in abundant expression of adhesion molecules (selectin,VCAM-1,ICAM-1) and stimulates production of chemokines as well as a wide range of cytokines (Aukrust et al, 2004; Lievens et al, 2009). SCD40L enhances agonist-induced activation and aggregation of human platelets via the CD40mediated tumor necrosis factor receptor–associated factor (TRAF)-2/Rac1/p38 mitogen-activated protein kinase (MAPK)-dependent pathway, which results in platelet activation (Yacoub et al, 2010)
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