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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.

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