Antitrypanosomal and cytotoxic activities of pyrrolizidine alkaloid-producing plants of Ethiopia.
OBJECTIVE
The objective was to determine the in-vitro effect of extracts from 19 Ethiopian plant species and four pure pyrrolizidine alkaloids on bloodstream forms of Trypanosoma brucei brucei and human leukaemia HL-60 cells.


METHODS
Crude plant extracts were prepared using methanol and dichloromethane. The alkaloidal extracts from Solanecio angulatus flowers were prepared with and without zinc reduction using the acid-base extraction method. Cell proliferation inhibitory activity of the extracts and compounds was assessed using Alamarblue.


RESULTS
The most active extract was the dichloromethane extract of Solanecio angulatus flowers, with an IC50 value of 12.17 microg/ml. The best selectivity index (SI > 41.08) was obtained for the same extract determined with HL-60 cells. The reduced alkaloidal extract prepared from S. angulatus flowers and after acid-base extraction showed more antitrypanosomal activity than unreduced alkaloidal extract with an IC50 value of 14.35 microg/ml and with a selectivity index of 12.23. The second most active extract was the dichloromethane extract of Crotalaria phillipsiae twigs with an IC50 value of 12.67 microg/ml and a selectivity index of 34.35. Most of the other extracts tested showed moderate antitrypanosomal activities to variable extents. Among the four pure pyrrolizidine alkaloids tested, senecionine showed moderate antitrypanosomal activity with an IC50 value of 41.78 microg/ml.


CONCLUSIONS
Solanecio angulatus (flowers) and Crotalaria phillipsiae (twigs) could serve as sources of novel trypanocidal compounds for the treatment of trypanosomiasis.
Nibret
Endalkachew
E
Institutut fur Pharmazie und Molekulare Biotechnologie, Universitst Heidelberg, im Neuenheimer Feld 364, Heidelberg, Germany.
Sporer
Frank
F
Asres
Kaleab
K
Wink
Michael
M
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D019659:Asteraceae / Q000737:chemistry*; D049109:Cell Proliferation / Q000187:drug effects; D029864:Crotalaria / Q000737:chemistry*; D005002:Ethiopia; D035264:Flowers / Q000737:chemistry; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D018547:Plant Stems / Q000737:chemistry; D011763:Pyrrolizidine Alkaloids / Q000494:pharmacology*; D014344:Trypanocidal Agents / Q000302:isolation & purification / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D011763:Pyrrolizidine Alkaloids; D014344:Trypanocidal Agents