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 anti-thrombotic 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. Additionally, isorhynchophylline (5 mg/kg) was injected into mice to measure in vivo hemostasis and thrombosis. Isorhynchophylline dose-dependently reduced platelet aggregation, ATP secretion, P-selectin expression and αIIbβ3 activation induced by collagen-related peptide (CRP) or thrombin without affecting surface level of receptors αIIbβ3, GPIbα, and GPVI. 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.