Anti-Trypanosoma Cruzi Activity: A Review of Herbal Products in Chagas Disease Treatment

Introduction: Chagas Disease (CD), or American trypanosomiasis, is an infection caused by the flagellated protozoan Trypanosoma cruzi. Current treatment relies on two nitroderivative drugs, Nifurtimox (Nf) and Benznidazole (BZ), which show partial efficacy in the acute phase and are associated with severe side effects. To develop safer and more effective treatments, natural products have been widely explored as potential trypanocidal agents. This review aims to explore the potential of plant-derived natural products as trypanocidal agents, emphasizing compounds with promising activity and selectivity that may serve as leads for the development of new drug candidates. Methods: A review of the literature published between 1995 and 2023 was conducted using PubMed, Google Scholar, and Scielo databases. Studies were included if they reported trypanocidal activity of plant-derived compounds with IC50 values below 10 μM or 100 μg/mL and favorable selectivity indices. The selected studies were analyzed based on the compounds in vitro and in vivo efficacy, effects on different life stages of T. cruzi, and inhibition of key enzymatic targets, such as cruzipain and trypanothione reductase. Results: A total of 110 compounds were identified, with significant effects on T. cruzi growth inhibition, in vivo efficacy, and enzymatic inhibition. Notably, several compounds targeted key metabolic enzymes, including cruzipain and trypanothione reductase. Discussion: Despite their potential, some active compounds contain electrophilic or amphipathic structures associated with non-specific cytotoxicity. Thus, selectivity and safety assessments are crucial. Additionally, synergistic effects with benznidazole were observed for certain compounds, suggesting potential for combination therapies. Conclusions: These findings underscore the potential of plant-derived substances as promising candidates for CD treatment. Many compounds exhibited strong or moderate trypanocidal activity, supporting their relevance in drug discovery and novel therapeutic strategies against T. cruzi.