Antileishmania and immunomodulatory potential of cashew nut shell liquid and cardanol

Conventional treatments for leishmaniasis have caused serious adverse effects, poor tolerance, development of resistant strains. Natural products have been investigated as potential therapeutic alternatives. The cashew nut shell liquid (CNSL) is a natural source of phenolic compounds with several biological activities, where cardanol (CN) is considered one of the most important and promising compounds. This study aimed to evaluate antileishmanial, cytotoxic and immunomodulatory activities of CNSL and CN. Both showed antileishmanial potential, with IC₅₀ for CNSL and CN against Leishmania infantum: 148.12 and 56.74 μg/mL; against Leishmania braziliensis: 85.71 and 64.28 μg/mL; against Leishmania major: 153.56 and 122.31 μg/mL, respectively. The mean cytotoxic concentrations (CC₅₀) of CNSL and CN were 37.51 and 31.44 μg/mL, respectively. CNSL and CN significantly reduced the percentage of infected macrophages, with a selectivity index (SI) >20 for CN. CNSL and cardanol caused an increase in phagocytic capacity and lysosomal volume. Survival rates of Zophobas morio larvae at doses of 3; 30 and 300 mg/kg were: 85%, 75% and 60% in contact with CNSL and 85%, 60% and 40% in contact with CN, respectively. There was a significant difference between the survival curves of larvae when treated with CN, demonstrating a significant acute toxicity for this substance. Additional investigations are needed to evaluate these substances in the in vivo experimental infection model.