Xinmailong Modulates Platelet Function and Inhibits Thrombus Formation via the Platelet αIIbβ3-Mediated Signaling Pathway

Abstract

Background: Xinmailong (XML), a bioactive composite extracted from Periplaneta americana , has been widely used to treat cardiovascular diseases such as congestive heart failure. However, it is unclear whether XML has antiplatelet and antithrombotic effects. Methods: The effects of XML on agonist-induced platelet aggregation, adhesion and spreading, granule secretion, integrin α II bβ3 activation, and thrombus formation were evaluated. Phosphorylation of Syk, PLCγ2, Akt, GSK3β, and MAPK signaling molecules was also studied on agonist-induced platelets. In addition, the antithrombotic effects of XML were observed in vivo using an acute pulmonary thrombosis mouse model. Results: XML dose-dependently inhibited in vitro platelet aggregation and granule secretion induced by thrombin, collagen, and arachidonic acid (AA). XML also greatly reduced platelet adhesion and spreading on both collagen- and fibrinogen-coated surfaces. Biochemical analysis revealed that XML inhibited thrombin-, collagen-, and AA-induced phosphorylation of Syk, PLCγ2, Akt, GSK3β, and MAPK. Additionally, XML significantly inhibited in vivo thrombus formation in a collagen–epinephrine-induced acute pulmonary thrombosis mouse model. Conclusions and General Significance: Here, we provide the first report showing that XML inhibits platelet function and that it possesses antithrombotic activity. This suggests that XML could be a potential therapeutic candidate to prevent or treat platelet-related cardiovascular diseases.

RETRACTED: Protective Effect of Xinmailong Injection on Rats With Myocardial Infarction

“…The anti-myocardial ischemia effect of Xinmailong may be related to the antiplatelet aggregation. Some research showed that platelet adherence to immobilized collagen-coated surfaces was decreased by Xinmailong and it inhibited collagen-, thrombin-, and AA-induced platelet aggregations in a dose-dependent fashion ( Wang et al, 2019 ). In addition, Xinmailong was reported to reduce myocardial expression of hypoxia-induced factor-1α (HIF-1α) and decrease plasma endothelin-1 (ET-1) levels, so as to alleviate hypoxia-ischemic myocardial injury ( Qi et al, 2017 ).…”

“…A series of clinical trials performed in HF patients confirmed the effectiveness of Xinmailong in improving cardiac function, such as enhancement of myocardial contraction and inhibition of ventricular remodeling ( Lu et al, 2018 ). It was reported that Xinmailong could inhibit platelet function and has antithrombotic activity, could be a potential therapeutic candidate to prevent or treat platelet-related cardiovascular diseases ( Wang et al, 2019 ). Clinical outcome revealed that Xinmailong injection has certain protective effects on cardiac dysfunction.…”

Construction of multifunctional porcine acellular dermal matrix hydrogel blended with vancomycin for hemorrhage control, antibacterial action, and tissue repair in infected trauma wounds

“…As the ECM hydrogels derived form porcine skin possesses good plasticity, injectability, biocompatibility and renewability, it can be applied to irregular skin tissue injuries and accelerate tissue healing [ [26] , [27] , [28] , [29] ]. Moreover, ECM is closely related to thrombosis [ 30 ]; under certain physiological conditions, the exposure of subcutaneous ECM and the subsequent platelet accumulation influence the control of hemorrhage [ [31] , [32] , [33] ]. Thus, ECM proteins (including fibrin, fibronectin, collagen, etc.)…”

Naringenin Inhibits Platelet Activation and Arterial Thrombosis Through Inhibition of Phosphoinositide 3-Kinase and Cyclic Nucleotide Signaling

“…Flow cytometric assays were performed as described previously ( Wang et al, 2019 ). ADP-stimulated P-selectin exposure and fibrinogen binding were determined in washed platelets.…”