Trypanosomatid parasites—particularly Trypanosoma and Leishmania species—are causative agents of several Neglected Tropical Diseases (NTDs) that impose substantial health and economic burdens on both humans and livestock across endemic regions. With no vaccines available and current chemotherapy is limited by toxicity, and widespread resistance. The need for sustainable, cross-species therapeutics is urgent. Guided by the One Health approach, which integrates human, animal, and environmental health, we investigated the antiparasitic potential of propolis-derived natural products.
Propolis is a complex resinous material produced by bees from local vegetation. It varies in composition depending on geographical and botanical sources. Using liquid chromatography coupled with high-resolution mass spectrometry (LC-MS), followed by principal component analysis (PCA), we profiled propolis samples collected from diverse geographical regions. This analysis revealed significant chemical diversity among samples. Orthogonal partial least squares (OPLS) regression analysis further identified bioactivity-associated markers: a butyrate ester of pinobanksin was linked to strong activity against T. brucei, while methyl ethers of chrysin and pinobanksin were associated with activity against T. congolense.
Our results indicate that the principal bioactive constituents across these samples are flavonoids—particularly phenolic compounds—which appear responsible for the observed broad-spectrum antiparasitic activity. Both crude and fractionated propolis extracts exhibited potent in vitro efficacy against Trypanosoma and Leishmania species, with low half-maximal effective concentrations (EC₅₀) and no detectable cytotoxicity to mammalian cells. Moreover, these compounds retained activity against drug-resistant strains, including diamidine-, arsenical-, and phenanthridine-resistant T. brucei, as well as miltefosine-resistant L. mexicana.
Altogether, these findings highlight propolis as a promising reservoir of flavonoid-based compounds for the rational development of safe, sustainable, and cross-species drugs targeting trypanosomatid diseases. This work supports a One Health-aligned strategy for integrated disease control and natural product drug discovery.
