In Vitro Activity of Gallic Acid-Paromomycin Combination Against Leishmania guyanensis and Human Cell Lymphoproliferative Primary Immune Response

Cutaneous leishmaniasis remains a therapeutic challenge due to toxicity, parasitic resistance, and the limitations of conventional drugs. In this context, combination therapies using natural immunomodulatory compounds have emerged as a promising alternative. This study evaluated the antileishmanial, cytotoxic, and immunomodulatory effects of gallic acid (GA) combined with paromomycin sulfate (PAR) using in vitro models. IC50 values were determined in promastigote and amastigote forms of Leishmania (Viannia) guyanensis, and CC50 values were assessed in RAW 264.7 macrophages. Peripheral blood mononuclear cells (PBMCs) from healthy volunteers (n = 13) were stimulated with GA, PAR, GA + PAR, or controls to evaluate lymphoproliferation and cytokine production. GA showed higher activity against intracellular amastigotes (IC50 = 11.4 µM), while GA + PAR also demonstrated activity (IC50 = 20.5 µM). PAR alone showed limited efficacy. The combination exhibited limited antiparasitic activity, with effects mainly at higher concentrations and without consistent superiority over GA monotherapy. Immunologically, GA + PAR displayed a balanced cytokine profile without inducing excessive proliferation. These findings suggest a complementary immunomodulatory effect, although further studies are needed to confirm its therapeutic relevance.