In vitro activity of cinnamaldehyde on Leishmania (Leishmania) amazonensis

Tegumentary leishmaniasis is an endemic disease that urgently needs new and effective treatments. L. amazonensis is one of the main species involved in the transmission of this infectious and non-contagious disease. The currently available treatments for leishmaniasis have high toxicity and vary in efficacy. Natural compounds have been used as alternative therapies for various other diseases, often presenting excellent results with little or no adverse reaction. Cinnamaldehyde is the primary compound of essential oil from cinnamon bark; it is used in the cosmetic, pharmaceutical, and food industries for its antimicrobial and anti-inflammatory effects, as shown in the literature. As far as we know, no studies have evaluated cinnamaldehyde activity against L. amazonensis. In this context, we investigated the anti-Leishmania potential of cinnamaldehyde against promastigote and amastigote forms of L. amazonensis; cytotoxicity in erythrocytes, HaCat cells, and macrophages J774A.1; and its ability to stimulate nitric oxide. Cinnamaldehyde showed anti-Leishmania activity, with an average IC₅₀ of approximately 212 μM against promastigote forms of L. amazonensis (three study periods: 24, 48, and 72 h) and an IC₅₀ of 398.06 ± 42.10 μM against amastigote forms of L. amazonensis. Considerable toxicities to human erythrocytes and HaCat cells were not recorded from treatments with 4000 μM and 1000 μM of cinnamaldehyde, respectively. However, we recorded cytotoxicity with J774A.1 macrophages (0.48-1000 μM), which resulted in a low therapeutic selectivity index. The compound did not alter the production of nitric oxide in the cells evaluated. Overall, we observed that cinnamaldehyde showed anti-Leishmania activity and moderate toxicity. We encourage further research into the use of cinnamaldehyde to treat cutaneous leishmaniasis.