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

Abstract

In this study we demonstrated the potential association effect of conventional amphotericin B (Amph B) and Gallic acid (GA) or Ellagic acid (EA) in topical formulation for treatment of cutaneous leishmaniasis in BALB/c mice. Preliminary stability tests and in vitro drug release studies with Amph B, GA, Amph B + GA, EA and Amph B + EA in the composition and in vivo treatment of BALB/c mice infected by Leishmania major were performed. After 40 days of infection, the animals were divided into 6 groups, treated 2x/day, for 21 days with the gel of Amph B, GA, Amph B + GA, EA and Amph B + 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. In the histopathological analysis of the treatments with GA, EA and associated Amph B, circumscribed lesion with presence of fibroblasts, granulation tissue and collagens deposition, as well as presence of activated macrophages. The formulations containing GA and EA activated macrophages in all evaluated parameters, resulting, therefore, in the activation of cells of the innate immune response, which can generate healing and protection. GA and EA produced an association effect with Amph B, which makes them promising their use with conventional Amph B in the treatment of cutaneous leishmaniasis.

Natural Products That Target the Arginase in Leishmania Parasites Hold Therapeutic Promise

“…ECGC showed similar efficacy as Glucantime, which was used as a control drug [ 108 ]. GA was tested in a topical formulation in female BALB/c mice infected with L. major and demonstrated reduction in lesion size and parasite burden [ 119 ]. The study also tested amphotericin B in a topical formulation as control drug and GA showed similar efficacy [ 119 ].…”

“…GA was tested in a topical formulation in female BALB/c mice infected with L. major and demonstrated reduction in lesion size and parasite burden [ 119 ]. The study also tested amphotericin B in a topical formulation as control drug and GA showed similar efficacy [ 119 ]. Interestingly, the number of parasites remained lower several days after ending the treatment when GA was used; this did not occur with amphotericin B treatment [ 119 ].…”

“…The study also tested amphotericin B in a topical formulation as control drug and GA showed similar efficacy [ 119 ]. Interestingly, the number of parasites remained lower several days after ending the treatment when GA was used; this did not occur with amphotericin B treatment [ 119 ]. The authors attribute this to the immune modulatory effect of GA because ex vivo investigation of skin fragments showed macrophage activation in GA treated mice [ 119 ].…”

“…Interestingly, the number of parasites remained lower several days after ending the treatment when GA was used; this did not occur with amphotericin B treatment [ 119 ]. The authors attribute this to the immune modulatory effect of GA because ex vivo investigation of skin fragments showed macrophage activation in GA treated mice [ 119 ]. Importantly, none of these studies observed toxicities in the treated animals, advocating for the safety of EGCG and GA as anti-leishmanial treatments.…”

“…The green tea polyphenols also show encouraging results. EGCG and GA have been tested in mice infected with L. amazonensis , L. braziliensis or L. major and resulted in significant reductions in lesion size and parasite burden [ 108 , 115 , 116 , 119 ]. EGCG was evaluated in three studies; one study applied a topical formulation [ 116 ] and two studies used oral delivery [ 108 , 115 ].…”