title: A novel function for kojic acid, a secondary metabolite from Aspergillus fungi, as antileishmanial agent.
abstract: Kojic acid (KA) is a fungal metabolite used as a topical treatment skin-whitening cosmetic agent for melasma in humans; however its potential as an anti-leishmanial agent is unknown. Chemotherapy is one of the most effective treatments for Leishmaniasis. However, the drugs available are expensive, invasive, require long-term treatment and have severe side effects. Thus, the development of new effective leishmanicidal agents is a necessity. In this study we investigated the anti-leishmanial effect of KA on L. amazonensis, following in vitro and in vivo infections. KA (50 μg/mL) was found to decrease the growth by 62% (IC50 34 μg/mL) and 79% (IC50 27.84 μg/mL) of promastigotes and amastigotes in vitro, respectively. Ultrastructural analysis of KA-treated amastigotes showed the presence of vesicles bodies into the flagellar pocket, and an intense intracellular vacuolization and swelling of the mitochondrion. During the in vitro interaction of parasites and the host cell, KA reverses the superoxide anions (O2-) inhibitory mechanism promoted by parasite. In addition, 4 weeks after KA-topical formulation treatment of infected animals, a healing process was observed with a high production of collagen fibers and a decrease in parasite burden. Thus, these results demonstrated the great potential of KA as an anti-leishmanial compound.
authors.affiliation: Universidade Federal do Pará, Instituto de Ciências Biológicas, Laboratório de Biologia Estrutural, Belém, Pará, Brazil; Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Bioimagem, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil; Laboratório de Microscopia Eletrônica, Instituto Evandro Chagas, Secretaria de Vigilância em Saúde do Ministério da Saúde, Belém, Pará, Brazil.
authors.forename: Ana Paula D
authors.initials: AP
authors.lastname: Rodrigues
authors.affiliation: Universidade Federal do Pará, Instituto de Ciências Biológicas, Laboratório de Biologia Estrutural, Belém, Pará, Brazil; Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Bioimagem, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Luis Henrique S
authors.initials: LH
authors.lastname: Farias
authors.affiliation: Universidade Federal do Pará, Instituto de Ciências Exatas e Naturais, Laboratório de Investigação Sistemática em Biotecnologia e Biodiversidade Molecular do Instituto de Ciências Exatas e Naturais, Belém, Pará, Brazil.
authors.forename: Antonio Sérgio C
authors.initials: AS
authors.lastname: Carvalho
authors.affiliation: Universidade Federal do Pará, Instituto de Ciências Exatas e Naturais, Laboratório de Investigação Sistemática em Biotecnologia e Biodiversidade Molecular do Instituto de Ciências Exatas e Naturais, Belém, Pará, Brazil.
authors.forename: Alberdan S
authors.initials: AS
authors.lastname: Santos
authors.affiliation: Universidade Federal do Pará, Instituto de Ciências Biológicas, Laboratório de Neuroquímica Molecular e Celular, Belém, Pará, Brazil.
authors.forename: José Luiz M
authors.initials: JL
authors.lastname: do Nascimento
authors.affiliation: Universidade Federal do Pará, Instituto de Ciências Biológicas, Laboratório de Biologia Estrutural, Belém, Pará, Brazil; Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Bioimagem, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Edilene O
authors.initials: EO
authors.lastname: Silva
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D001230:Aspergillus / Q000378:metabolism*; D002626:Chemistry, Pharmaceutical; D003094:Collagen / Q000096:biosynthesis; D006224:Cricetinae; D005260:Female; D007891:Leishmania / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000469:parasitology; D051379:Mice; D011753:Pyrones / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D064210:Secondary Metabolism; D013481:Superoxides / Q000378:metabolism
chemical_list: D000981:Antiprotozoal Agents; D011753:Pyrones; D013481:Superoxides; C011890:kojic acid; D003094:Collagen