Columbin inhibits cholesterol uptake in bloodstream forms of Trypanosoma brucei-A possible trypanocidal mechanism.
The diterpenoid furanolactone (columbin) from Aristolochia albida inhibited growth of culture forms of Trypanosoma brucei. In vitro analysis of the compound at 5-250 microg/ml showed complete lysis of the parasites within 10-20 minutes post incubation. At 50 microg/ml, columbin killed about 50% of the parasites which initially appeared swollen under phase contrast microscopy. Also the total amount of cholesterol diminished dose-dependently in the presence of 10-100 microg/ml of columbin after a 3-day incubation period. In vivo analysis of the compound in T. brucei-infected mice revealed that 25 mg/kg administered for 3 consecutive days, completely cleared the parasites from the peripheral circulation. However, columbin could not clear parasites in the cerebrospinal fluid.
Nok
A J
AJ
Department of Biochemistry, Ahmadu Bello University, Zaria, Nigeria. jandrew@mail.skannet.com
Sallau
B A
BA
Onyike
E
E
Useh
N M
NM
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism*; D004224:Diterpenes / Q000494:pharmacology*; D007783:Lactones / Q000494:pharmacology*; D051379:Mice / Q000097:blood / Q000469:parasitology; D008858:Microscopy, Phase-Contrast; D013261:Sterols / Q000378:metabolism*; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects*; D014352:Trypanosomiasis / Q000188:drug therapy*
D004224:Diterpenes; D007783:Lactones; D013261:Sterols; D014344:Trypanocidal Agents; D002784:Cholesterol; C062514:columbin