Journal
PHYTOMEDICINE
Volume 96, Issue -, Pages -Publisher
ELSEVIER GMBH
DOI: 10.1016/j.phymed.2021.153900
Keywords
Trypanosoma cruzi; Sesquiterpenelactones; Antiparasitic activy; Trypanocidal activity
Categories
Funding
- National Scientific and Technical Research Council [PIP 11220150100158CO]
- University of Buenos Aires [UBACYT 20020170200316BA]
Ask authors/readers for more resources
The study demonstrates that both eupatoriopicrin and estafietin have additive effects on T. cruzi, suggesting that each compound acts on different primary targets. The combination treatment of eupatoriopicrin and estafietin could be considered a promising alternative for the treatment of Chagas' disease.
Background: : The sesquiterpene lactones (STLs) eupatoriopicrin (EP) and estafietin (ES), isolated from Stevia alpina Griseb. (Asteraceae) and Stevia maimarensis (Hieron.) Cabrera (Asteraceae) respectively, have previously showed promising trypanocidal activity, both in vitro and in vivo. Purpose: : In this work, using biochemical studies and electron microscopy, we aimed at characterizing the mode of action of both STLs on Trypanosoma cruzi. Methods: : The interaction of STLs with hemin was examined by measuring modifications in the Soret absorption band of hemin; the thiol groups interaction was determined spectrophotometrically through its reaction with 5,5'-dithiobis-2-nitrobenzoate; the effect on cruzipain activity was also assayed by spectrophotometry. The synthesis of sterols were qualitatively and quantitatively tested by TLC. Mitochondrial functionality was assessed by measuring mitochondrial membrane potential and the activity of NADH-cytochrome c reductase and succinate-cytochrome c reductase enzymes. The status of the antioxidant system was assessed by quantifying the level of free thiols by spectrophotometry, together with the intracellular oxidative state by flow cytometry. Ultrastructural changes were analyzed by transmission electron microscopy.. Results: : EP and ES were found to impair the functionality and the redox status of the parasite. ES produced a greater decrease in the activity of succinate dehydrogenase than eupatoriopicrin, affecting the functioning of the respiratory chain and the Krebs cycle. EP increased the formation of triglycerides leading to the presence of cytoplasmic lipid droplets. By electron microscopy, alterations in the kinetoplast and the appearance of large translucent vacuoles in the cytoplasm were observed for both compounds. Conclusions: : Both sesquiterpenelactones proved to act additively on T. cruzi, supporting the hypothesis that each compound would be acting on different primary targets.. The treatment combining eupatoriopicrin and estafietin could be considered a promising alternative for the treatment of Chagas' disease.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available