Neolignan Licarin A presents effect against Leishmania (Leishmania) major associated with immunomodulation in vitro

• Published in: Experimental parasitology Vol. 135; no. 2; pp. 307 - 313
• Main Authors: Néris, Patrícia L.N., Caldas, John P.A., Rodrigues, Yara K.S., Amorim, Francianne M., Leite, Jacqueline A., Rodrigues-Mascarenhas, Sandra, Barbosa-Filho, José M., Rodrigues, Luis C., Oliveira, Márcia R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-10-2013
• Subjects: adverse effects; amastigotes; amphotericin B; Amphotericin B - pharmacology; Animals; Antiprotozoal Agents - pharmacology; Antiprotozoal Agents - toxicity; Apoptosis; Cytokines - metabolism; Cytotoxicity; death; DNA; DNA Fragmentation; drugs; Female; IL-10; IL-6; Immunologic Factors - pharmacology; Immunologic Factors - toxicity; immunomodulation; Inhibitory Concentration 50; interleukin-10; Leishmania (Leishmania) major; Leishmania major; Leishmania major - drug effects; Leishmania major - genetics; leishmaniasis; Leishmaniasis, Cutaneous - drug therapy; Licarin A; Lignans - pharmacology; Lignans - toxicity; Macrophage; macrophages; Macrophages, Peritoneal - drug effects; Macrophages, Peritoneal - immunology; Macrophages, Peritoneal - parasitology; Meglumine - pharmacology; Meglumine - toxicity; Mice; Mice, Inbred BALB C; Nitric Oxide - metabolism; Organometallic Compounds - pharmacology; Organometallic Compounds - toxicity; parasites; parasitology; promastigotes; Cytotoxicity; Leishmania (Leishmania) major; Licarin A; IL-6; IL-10; Macrophage
• ISSN: 0014-4894; 1090-2449
• DOI: 10.1016/j.exppara.2013.07.007

•Licarin A inhibits the proliferation of Leishmania (L.) major promastigotesin vitro.•This neolignan induces DNA fragmentation on L. (L.) major promastigotes.•Licarin A is more effective against L. (L.) major intracellular amastigotes.•Decrease in IL-6 and IL-10 cytokines levels suggest immunomodulation by licarin A.
Leishmaniasis’ treatment is based mostly on pentavalent antimonials or amphotericin B long-term administration, expensive drugs associated with severe side effects. Considering these aforementioned, the search for alternative effective and safe leishmaniasis treatments is a necessity. This work evaluated a neolignan, licarin A anti-leishmanial activity chemically synthesized by our study group. It was observed that licarin A effectively inhibited Leishmania (Leishmania) major promastigotes (IC50 of 9.59±0.94μg/mL) growth, by inducing in these parasites genomic DNA fragmentation in a typical death pattern by apoptosis. Additionally, the neolignan proved to be even more active against intracellular amastigotes of the parasite (EC50 of 4.71±0.29μg/mL), and significantly more effective than meglumine antimoniate (EC50 of 216.2±76.7μg/mL) used as reference drug. The antiamastigote activity is associated with an immunomodulatory activity, since treatment with licarin A of the infected macrophages induced a decrease in the interleukin (IL)-6 and IL-10 production. This study demonstrates for the first time the antileishmanial activity of licarin A and suggests that the compound may be a promising in the development of a new leishmanicidal agent.