Antileishmanial Activity of Bioactive Compounds Obtained from Azadirachta indica and Cnidoscolus spp.: Systematic Review.

Leishmaniasis, a poorly studied tropical disease, has major therapeutic limitations, driving the search for safer, effective treatments. This review assessed scientific evidence on the antileishmanial activity of extracts, fractions, and bioactive compounds from Azadirachta indica and Cnidoscolus spp. in in vitro and in vivo studies. Following PRISMA 2020 guidelines, searches were conducted in PubMed/MEDLINE, Scopus, ScienceDirect, and Google Scholar. Eligible studies reported quantitative outcomes, including IC50/EC50 values, percentage inhibition, parasite load reduction, cytotoxicity, or selectivity index. Systematic reviews, studies without quantitative data, and unvalidated in silico studies were excluded. Overall, 87 records were identified, and 14 studies were included in the synthesis. Most evidence focused on A. indica derivatives tested against different Leishmania species, mainly in vitro, although some studies used BALB/c and CD-1, mouse models. Active fractions generally showed greater potency against intracellular amastigotes than promastigotes, with activity varying by fraction and model. In vivo studies with A. indica preparations reported reduced parasite loads and improved lesions. Evidence for Cnidoscolus spp. was limited and variable. Overall, plant-derived compounds show promising antileishmanial potential, but rigorous comparative studies are needed to strengthen evidence-based phytopharmaceutical development for leishmaniasis and to clarify the most active compounds, doses, formulations, and therapeutic targets across models.