Abstract
In our previous study, two known piperidine alkaloids (+)-spectaline (1) and iso-6-spectaline (2) were isolated from the leaves of Senna spectabilis and showed no toxic effect on L6 cells. In view of the potential use of piperidine alkaloids in S. spectabilis for the treatment of sleeping sickness, further investigation on the cell death actions of the parasite after treatment with compound 1 and 2 suggested that the treated parasites died by a process of autophagy based on the characteristic morphological alterations observed in intracellular T. b. rhodesiense. In search for apoptosis, interestingly, trypanosomes treated with high concentration of compound 1 and 2 after 72 h significantly induced an early apoptosis-like programmed cell death (PCD) such as phosphatidylserine (PS) exposure, loss of mitochondrial membrane potential and caspases activation. No DNA laddering discriminated late apoptosis event. Taken together, these findings demonstrated the potential of compound 1 and 2 as a natural chemotherapeutic capable of inducing a possible cross-talk between autophagy and apoptosis in T. b. rhodesiense.
Highlights
Human African Trypanosomiasis (HAT) known as “sleeping sickness” is caused by two protozoan parasites, Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense
Trypanosomes treated with IC90 of compound 1 and 2 after 72 h exhibited an effect that significantly induced an early apoptosis-like programmed cell death (PCD), which included phosphatidylserine (PS) exposure, loss of mitochondrial membrane potential, and caspases activation. These findings demonstrated the potential of compound 1 and 2 as a natural chemotherapeutic. capable of inducing a possible cross-talk between autophagy and apoptosis in T. b. rhodesiense
In view of the potential use of piperidine alkaloids in S. spectabilis for the treatment of sleeping sickness, further investigation into the cell death actions of the parasite after treatment with compound 1 and 2 suggested that the treated parasites died by a process of autophagy based on the characteristic morphological alterations observed in intracellular T. b. rhodesiense
Summary
Human African Trypanosomiasis (HAT) known as “sleeping sickness” is caused by two protozoan parasites, Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense. Rhodesiense without toxic effect on mammalian L6 cells It can be considered a potential candidate for HAT early drug discovery. Trypanosomes treated with IC90 of compound 1 and 2 after 72 h exhibited an effect that significantly induced an early apoptosis-like PCD, which included phosphatidylserine (PS) exposure, loss of mitochondrial membrane potential, and caspases activation. Taken together, these findings demonstrated the potential of compound 1 and 2 as a natural chemotherapeutic. Quantitative analysis of FITC fluorescence was done to show the PS exposure
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