Buddleja globosa Leaf Methanolic Extract Acts Against Trypanosoma cruzi Parasites by Inducing Mitochondrial Inner Membrane Hyperpolarization

The neglected Chagas disease, a zoonosis caused by the <i>Trypanosoma cruzi</i> 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 <i>Buddleja globosa</i>, evaluating the antioxidant activities and biological effects of its methanolic extract (MET) and BG500, an enriched iridoid fraction (6-<i>O</i>-methylcatalpol), against <i>T. cruzi</i> 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 <i>T. cruzi</i>'s Old Yellow (OYE) could be a potential target for 6-<i>O</i>-methylcatalpol. This work provides the first report on the potential trypanocidal activity of a <i>B. globosa</i> extract, highlighting the need for further studies to connect ΔΨm and OYE inhibition to the effects of 6-<i>O</i>-methylcatalpol.