Allium macrostemon Saponin Inhibits Activation of Platelet via the CD40 Signaling Pathway

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.

A Neonatal Mouse Model for Pressure Overload: Myocardial Response Corresponds to Severity

“…Western blot analysis was performed as described in a previous study (31). Briefly, the ventricular heart tissue was collected and dissected 7 and 14 days after TAC.…”

Saponins as therapeutic candidates for atherosclerosis

“…Clinical trials have shown that Allium macrostemon saponin decreases platelet activity markers such as CD63 and TXB2 by blocking the activation of downstream proteins in CD40L/CD40 pathways, including PI3K, p-Akt, p-p38, p-JNK, and NF-κB. This leads to the modulation of TRAF2-associated ubiquitination degradation, thereby exerting an anti-thrombotic effect in atherosclerosis (Ling et al, 2020).…”

Co-stimulators CD40-CD40L, a potential immune-therapy target for atherosclerosis: A review

“…[64,65] For vascular smooth muscle cells, ligation of CD40 can induce the production of metalloproteinases to promote plaque rupture, [66] and CD40 signaling can activate the Src family kinase pathway, leading to the induction of MAPK activities. [33,67] Platelets are one kind of important component in the circulatory system and play a crucial role in the inflammatory response and atherosclerotic plaque formation. [68,69] In addition to T cells, platelets are the primary source of CD40L in both the circulation and tissues.…”

“…[ 64 , 65 ] For vascular smooth muscle cells, ligation of CD40 can induce the production of metalloproteinases to promote plaque rupture, [ 66 ] and CD40 signaling can activate the Src family kinase pathway, leading to the induction of MAPK activities. [ 33 , 67 ]…”

“…Upon activation, platelets release clotting proteins, proinflammatory cytokines, and chemokines that contribute to the recruitment of monocytes to atherosclerotic arteries and accelerate plaque formation. [ 33 ] The interaction between CD40L on platelets and CD40 on endothelial cells can trigger various inflammatory responses, including the expression of adhesion molecules and inflammatory cytokines, such as ICAM-1, MCP-1, IL-6, IL-8, and matrix metalloproteinases. [ 52 , 70 , 71 ] During endothelium-platelet-monocyte interactions in the early stage of atherosclerosis, endothelial CD40 expression plays a crucial role in determining the atherosclerotic susceptibility sites.…”