Analysis of leishmanicidal and immunomodulatory activity of natural and synthetic products
Leishmania amazonensis, Treatment, immunomodulatory activity
Leishmaniases are a group of clinical manifestations caused by the parasite of the genus Leishmania. The World Health Organization (WHO) assumes that this disease affects 700 to 1 million individuals in vulnerable conditions annually. For infect several mammals, including man, it is considered a zoonosis with great impact on public health, where the main reservoir is the domestic dog. The treatments have several problems such as difficult administration, high toxicity and cost and cases of resistance have been reported. Given this scenario, the search for alternative treatments for leishmaniasis that can effectively eliminate the parasite and promote a satisfactory immune response in the host is necessary In this work, we analyzed the leishmanicidal activity of the sesquiterpene guayol isolated from the essential oil of Aloysia gratissima and of piperine (AF1) an amide found in the oil of Piper nigrum and its synthetic derivative N4-cyclohexyl-1,2,4-triazole-3- thione (AF2) formed from a hybridization with prothioconazole in Leishmania amazonensis one of the etiological agents of LTA in the New World in vitro together with its immunomodulatory activity in murine and dog macrophages through the expression of MHC receptors, Toll-like and inflammatory cytokines. Preliminary results show that (-)-Guaiol, AF1 and AF2 compounds have leishmanicidal activity with IC50 of 56.24 µM, 9.36 µM and 8.73 µM respectively. Macrophages showed no significant loss of viability after treatment with compounds remaining above 70%. Cytometry analyzes in unstimulated, LPS-stimulated or infected with L. amazonensis P388D1 cells indicate that there was a decrease in the population of MHCI + cells treated with 60 µM of AF1, AF2 and AF2+LPS. There was an increase in the population of MHCII+ cells treated with AF2, AF2+LPS and infected with L.a and treated with AF2. In double positive populations, there was an increase in treatment with AF1, AF2 and AF2+LPS. Finally, real-time PCR results demonstrate that unstimulated P388D1 cells treated with (-)-Guaiol increased IL-1β expression. AF1 led to reduced expression of TLR4 in cells after treatment. Preliminary results suggest that the compounds can modulate the immune profile of P388D1 lineage cells.