Pharmacological characterization of cepharanthin in chronic idiopathic thrombocytopenic purpura.
Cepharanthin, a bisbenzylisoquinoline (biscolaurine) alkaloid drug, has been reported to improve the symptoms of intractable or steroid-resistant chronic idiopathic thrombocytopenic purpura (ITP). To clarify the mechanism by which the cepharanthin is beneficial to ITP, we examined the effects of cepharanthin on thrombocytopenia in (NZW x BXSB) F1 (W/B F1) mice and on the formation of colony forming unit of megakaryocyte (CFU-MK) derived from human CD34-positive progenitor cells. The decrease in platelet numbers in W/B F1 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. From the data in this animal model, it is suggested that cepharanthin may prolong 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 thrombopoietin, 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 isolated 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 not only on the platelet destruction process, but also on the platelet production process of thrombocytopenia in chronic ITP.
Sato
T
T
Department of Cellular Physiological Chemistry, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
Morita
I
I
Fujita
H
H
Ono
M
M
Kimishima
A
A
Tomiyama
J
J
Murota
S
S
D000470:Alkaloids / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D018952:Antigens, CD34 / Q000097:blood; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use; D044182:Benzylisoquinolines; D001772:Blood Cell Count; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008297:Male; D008533:Megakaryocytes / Q000166:cytology; D051379:Mice; D008815:Mice, Inbred Strains; D010976:Platelet Count; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000188:drug therapy*; D013926:Thrombopoietin / Q000494:pharmacology; D052117:Benzodioxoles
D000470:Alkaloids; D018952:Antigens, CD34; D000972:Antineoplastic Agents, Phytogenic; D044182:Benzylisoquinolines; D007377:Interleukin-3; D015850:Interleukin-6; D013926:Thrombopoietin; C006947:cepharanthine; D052117:Benzodioxoles