Pharmacological characterization of cepharanthin in chronic idiopathic thrombocytopenic purpura

Cepharanthin, a bisbenzylisoquinoline (biscolaurine) alkaloid drug, has bee n reported to improve the symptoms of intractable or steroid-resistant chro nic idiopathic thrombocytopenic purpura (ITP). To clarify the mechanism by which the cepharanthin is beneficial to ITP, we examined the effects of cep haranthin on thrombocytopenia in (NZW x BXSB) F1 (W/B F1) mice and on the f ormation of colony forming unit of megakaryocyte (CFU-MK) derived from huma n CD34-positive progenitor cells. The decrease in platelet numbers in W/B F 1 was diminished by the administration of 5 mg/kg cepharanthin for 6 weeks as well as by 2 mg/kg prednisolone. Furthermore, the administration of over 0.2 mg/kg cepharanthin enhanced the therapeutic effect of prednisolone. Fr om the data in this animal model, it is suggested that cepharanthin may pro long the platelet lifespan. The treatment of CD34-positive progenitor cells isolated from cord blood with cepharanthin (over 5 x 10(-10) g/ml) caused an increase in the formation of CFU-MK induced by the cocktail of thrombopo ietin, interleukin (IL)-6 and IL-3. The addition of 0.1% normal human serum dramatically increased the number of CFU-MK. In contrast, the serum isolat ed from patients with ITP at the same concentration decreased the number of CFU-MK. However, the simultaneous addition of 5 x 10(-8) g/ml cepharanthin recovered the number of CFU-MK to the level induced by normal serum. These findings indicate that cepharanthin has the potent therapeutic activity no t only on the platelet destruction process, but also on the platelet produc tion process of thrombocytopenia in chronic ITP.