Isorhynchophylline Inhibits Platelet Activation and Thrombus Formation.

Isorhynchophylline is a Chinese herbal medicine and has multiple effects such as anti-inflammatory and neuroprotective effects. Whether isorhynchophylline has antithrombotic property is unknown. This study aims to evaluate its role in platelet function. Human platelets were incubated with isorhynchophylline (0, 10, 20, and 40 μM) at 37°C for 1 hour to detect platelet aggregation and activation, receptors level, spreading, and calcium mobilization. In addition, isorhynchophylline (5 mg/kg) was injected into mice to measure in vivo hemostasis and thrombosis. Isorhynchophylline dose-dependently reduced platelet aggregation, adenosine triphosphate secretion, P-selectin expression, and α IIb β 3 activation induced by collagen-related peptide or thrombin without affecting surface level of receptors α IIb β 3 , GPIbα, and glycoprotein VI. Meanwhile, isorhynchophylline-treated platelets showed reduced spreading. Moreover, isorhynchophylline reduced platelet calcium mobilization, phosphatidylserine exposure, and the phosphorylation of PLCγ2 and PKCα. Furthermore, administration of isorhynchophylline into mice impaired platelet hemostatic function and arterial/venous thrombosis without affecting coagulation. In conclusion, isorhynchophylline impairs platelet function and arterial/venous thrombosis, implying its potential to be a novel agent for treating thrombotic or cardiovascular diseases.