Gallic and Ellagic Acids Are Promising Adjuvants to Conventional Amphotericin B for the Treatment of Cutaneous Leishmaniasis

• Published in: Antimicrobial agents and chemotherapy Vol. 64; no. 12
• Main Authors: Alves, Michel Muálem de Moraes, Arcanjo, Daniel Dias Rufino, Figueiredo, Kayo Alves, Oliveira, Jéssica Sara de Sousa Macêdo, Viana, Felipe José Costa, Coelho, Elvilene de Sousa, Lopes, Glaucia Lais Nunes, Gonçalves, Juan Carlos Ramos, Carvalho, André Luís Menezes, Rizzo, Márcia Dos Santos, Chaves, Mariana Helena, Mendonça, Ivete Lopes de, Carvalho, Fernando Aécio de Amorim
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 17.11.2020
• Subjects: Amphotericin B - pharmacology; Amphotericin B - therapeutic use; Animals; Antiprotozoal Agents - pharmacology; Antiprotozoal Agents - therapeutic use; Ellagic Acid - pharmacology; Experimental Therapeutics; Leishmania major; Leishmaniasis, Cutaneous - drug therapy; Mice; Mice, Inbred BALB C; phenolic compounds; poloxamer; drug association; leishmaniasis; activation of macrophages
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/aac.00807-20

In this study, we demonstrated the potential associative effect of combining conventional amphotericin B (Amph B) with gallic acid (GA) and with ellagic acid (EA) in topical formulations for the treatment of cutaneous leishmaniasis in BALB/c mice. Preliminary stability tests of the formulations and drug release studies with Amph B, GA, Amph B plus GA, EA, and Amph B plus EA were carried out, as well as assessment of the treatment of BALB/c mice infected with After 40 days of infection, the animals were divided into 6 groups and treated twice a day for 21 days with a gel containing Amph B, GA, Amph B plus GA, EA, or Amph B plus EA, and the negative-control group was treated with the vehicle. In the animals that received treatment, there was reduction of the lesion size and reduction of the parasitic load. Histopathological analysis of the treatments with GA, EA, and combinations with Amph B showed circumscribed lesions with the presence of fibroblasts, granulation tissue, and collagen deposition, as well as the presence of activated macrophages. The formulations containing GA and EA activated macrophages in all evaluated parameters, resulting in the activation of cells of the innate immune response, which can generate healing and protection. GA and EA produced an associative effect with Amph B, which makes them promising for use with conventional Amph B in the treatment of cutaneous leishmaniasis.