Antileishmania and immunomodulatory potential of cashew nut shell liquid and cardanol

Abstract

Leishmaniasis is a neglected disease caused by protozoa of the genus Leishmania, endemic in 98 countries, constituting a major public health problem. Conventional treatments cause serious adverse effects, poor tolerance, development of resistant strains, and are costly. Natural products have been investigated in the search for therapeutic alternatives. The cashew nut shell liquid (CNSL) is a natural source of phenolic compounds, showing antioxidant, anti-inflammatory, antimicrobials, antitumors, larvicides and insecticides, with cardanol (CN) being considered one of the most important and promising technical components. This study aimed to evaluate antileishmania, cytotoxic and immunomodulatory activities of CNSL and CN. The substances showed antileishmania potential, with values of mean inhibitory concentration (IC50) of 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, however, they did not exhibit significant induction of nitric oxide synthesis. 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.