Evaluation of antitrypanosomal properties and apoptotic effects of ochrolifuanine from Dyera costulata (Miq.) Hook.f against Trypanosoma brucei brucei
Document Type
Article
Publication Date
9-1-2022
Abstract
Trypanosoma brucei parasites are flagellated kinetoplastid protozoan which is responsible for Human African Trypanosomiasis (HAT). Current chemotherapy drugs have a number of side effects and drug resistance has emerged as a major issue in current treatment. Active bisindole alkaloid compound ochrolifuanine was previously isolated from the leaves of Dyera costulata. In vitro antitrypanosomal activity of ochrolifuanine against Trypanosoma brucei brucei strain BS221 showed strong activity with an IC50 value of 0.05 +/- 0.01 mu g/ml. We compared the effect of ochrolifuanine and reference compound staurosporine in T. b. brucei apoptosis. The apoptosis-inducing activity of ochrolifuanine was evaluated using TUNEL assay and cell cycle analysis. Trypanosoma brucei brucei was shown to undergo apoptotic cells death as demonstrated by the appearance of several conical hallmarks of apoptosis. Ochrolifuanine was found to induce apoptosis in parasites in a dose-and time-dependent manner. The cell cycle study revealed 0.025 and 0.05 mu g/ml of ochrolifuanine arrested the growth of T. b. brucei at two different growth phases (G0/G1 and in S phases). While at concentration 0.10 mu g/ml arrested at the G2/M phase. In conclusion, the results indicate that ochrolifuanine displayed an antitrypanosomal effect on T. b. brucei by inducing apoptosis cell death and causing the arrest of parasite cells at different growth phases. The results suggested that ochrolifuanine may be a promising lead compound for the development of new chemotherapies for African trypanosomiasis.
Keywords
Ochrolifuanine, Dyera costulata, apoptotic, Trypanosoma brucei brucei
Funders
Ministry of Energy, Science, Technology, Environment and Climate Change (MESTECC), Malaysia [09-05-IFN-BPH-003],Swiss Tropical and Public Health Institute (Switzerland)
Publication Title
Tropical Biomedicine
Volume
39
Issue
3
Publisher
Malaysian Society of Parasitology and Tropical Medicine
Publisher Location
21-5-2, BLOCK, E, DIAMOND SQUARE, JALAN 3-50, OFF JALAN GOMBAK, KUALA LUMPUR, MALAYSIA