Antiplatelet Effects of a Kampo Medicine, Orengedokuto

Introduction: Orengedokuto, a Kampo medicine, is used to treat patients with hypertension and cerebrovascular disease in Japan. One of its effects is thought to be antiplatelet action, but the mechanisms involved are unclear. Therefore, we investigated the effects of Orengedokuto on platelet aggregation and activation. Methods: Platelet aggregation was determined by measuring light transmission (optical density [OD]) and light scattering intensity. Platelet activation was assessed by flow-cytometric determination of PAC-1+ and CD62P+ platelets. For the in vitro study, blood samples were obtained from 45 patients with cerebral infarction (chronic stage) and 27 magnetic resonance imaging-proven control subjects. Furthermore, Orengedokuto was administered to 10 patients with cerebral infarction for up to 12 months, and its effects on platelet aggregation and activation were evaluated. Results: Orengedokuto dose-dependently inhibited agonist-induced platelet aggregation. In vitro, the OD% (mean ± SD) after stimulation with 2 μmol/L adenosine diphosphate was decreased from 54.4 ± 21.0 to 16.0 ± 14.2 (P < .01) in patients, and from 56.8 ± 26.9 to 19.8 ± 18.9 (P < .01) in control subjects (1000 μg/mL Orengedokuto). Similarly, the OD% after 0.5 μg/mL collagen stimulation was decreased from 98.3 ± 37.0 to 24.8 ± 27.9 (P < .01) in patients, and from 79.2 ± 13.8 to 21.5 ± 21.9 (P < .01) in the control subjects. In the clinical study, platelet aggregation was also significantly decreased (P < .05). Agonist-induced platelet activation was not significantly inhibited by Orengedokuto in vitro, but spontaneous platelet activation in patients after oral administration was reduced from 31.0 ± 18.3 to 14.2 ± 8.7 (PAC-1+) and from 11.3 ± 7.8 to 5.1 ± 3.9 (CD62+) (P < .05). Conclusion: Our results demonstrated inhibitory activity of Orengedokuto on both platelet aggregation and activation at a clinically relevant dose.