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Buddleja globosa Leaf Methanolic Extract Acts Against Trypanosoma cruzi Parasites by Inducing Mitochondrial Inner
Helena Quintero-Pertuz1,2, Vicente Valenzuela-Bass1, Michel Lapier3
1Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Dr. Carlos Lorca Tobar 964, Independencia, Santiago 8380492, Chile.
Insights
Chilean Buddleja globosa extract shows potential against Chagas disease. Its compounds demonstrated trypanocidal activity and mitochondrial effects, offering alternatives to current treatments.
Area of Science:
- Pharmacology
- Parasitology
- Natural Products Chemistry
Background:
- Chagas disease, caused by Trypanosoma cruzi, has limited and toxic treatment options.
- Natural products offer promising therapeutic alternatives, especially from Chile's diverse flora.
Purpose of the Study:
- To evaluate the antioxidant and trypanocidal effects of Buddleja globosa extract and its fractions against T. cruzi.
- To explore potential molecular targets and mechanisms of action.
Main Methods:
- Preparation and testing of methanolic extract (MET) and an enriched iridoid fraction (BG500, 6-O-methylcatalpol).
- Assessment of trypanocidal activity, selectivity index, and mitochondrial membrane potential (ΔΨm) changes.
- In silico molecular docking studies targeting T. cruzi Old Yellow Enzyme (OYE).
Main Results:
- The MET exhibited trypanocidal activity against T. cruzi trypomastigotes with a selectivity index comparable to nifurtimox.
- Both MET and BG500 induced hyperpolarization of mitochondrial membrane potential (ΔΨm).
- In silico studies suggest OYE as a potential target for 6-O-methylcatalpol.
Conclusions:
- Buddleja globosa extract and its fraction show potential as a source for Chagas disease therapeutics.
- Further research is needed to elucidate the link between ΔΨm changes, OYE inhibition, and the trypanocidal effects of 6-O-methylcatalpol.
Abstract:
The neglected Chagas disease, a zoonosis caused by the Trypanosoma cruzi parasite, has limited treatment options like nifurtimox and benznidazole, known for their toxic effects and controversial efficacy. Natural products present opportunities for therapeutic alternatives, particularly in Chile, which has a rich variety of endemic flora. This study focused on the Chilean Buddleja globosa, evaluating the antioxidant activities and biological effects of its methanolic extract (MET) and BG500, an enriched iridoid fraction (6-O-methylcatalpol), against T. cruzi trypomastigotes. Although the trypanocidal activity of the extract was significantly lower than that of nifurtimox (280 ± 3.5 vs. 5.0 ± 0.5), its selectivity was comparable (selectivity index > 15). The MET and enriched fraction also induced hyperpolarization of mitochondrial membrane potential (ΔΨm). In silico docking studies suggested that T. cruzi's Old Yellow (OYE) could be a potential target for 6-O-methylcatalpol. This work provides the first report on the potential trypanocidal activity of a B. globosa extract, highlighting the need for further studies to connect ΔΨm and OYE inhibition to the effects of 6-O-methylcatalpol.
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