Amburana cearensis (Cumaru) and Its Active Principles as Source of Anti-Leishmania Drugs: Immunomodulatory Activity of Coumarin (1,2-Benzopyrone)

<b>Background/Objectives</b>: In Brazil, <i>Leishmania braziliensis</i> is the main etiological agent of cutaneous leishmaniasis and represents an important public health problem. The actual pharmacotherapy of leishmaniasis has several disadvantages, making the development of new therapeutic options essential. The present study aimed to carry out the bioprospecting and selection of products of <i>Amburana cearensis,</i> including extracts and active principles with a leishmanicidal effect and to evaluate its possible mechanism of action. <b>Methods</b>: A dry extract of <i>A. cearensis</i> (DEAC) was characterized by HPLC, with the following active markers: coumarin (CM), amburoside A (AMR), and vanillic acid (VA). The leishmanicidal effect of DEAC was assessed, and the in vitro inhibitory action of the phenolic fraction, including CM, AMR, and VA, on promastigote and amastigote forms were determined. <b>Results</b>: CM showed the best reductions (maximal inhibition: 57%) of the promastigote form of <i>L. braziliensis</i>, followed by the plant extract (40% inhibition) and other test drugs (maximal reduction: 29%). The treatment of macrophages infected by <i>L. brasiliensis</i> with CM (10 μg/mL) reduced the intracellular parasite load (amastigote form, maximal reduction: 50%), increased the production of nitric oxide, TNF-α, IL-12, and IL-10, and decreased the production of IL-4. These effects were not related to cytotoxicity (MTT test). Glucantime (4 mg/mL, standard drug) reduced the amastigote form by 65%. <b>Conclusions</b>: CM showed promising leishmanicidal activity against both forms of <i>L. brasiliensis</i>, and this effect seems to be associated, at least in part, to its immunomodulatory action by tilting the Th1/Th2 imbalance in favor of Th1.