Macrophage activation and leishmanicidal activity by galactomannan and its oxovanadium (IV/V) complex in vitro

Compounds that activate macrophage antimicrobial activity are potential targets for treatment of leishmaniasis. The present study investigated the in vitro immunomodulatory effects of a galactomannan (GALMAN-A) isolated from seeds of Mimosa scabrella and its oxovanadium (IV/V) complex (GALMAN-A:VO2+/VO3+) on macrophage activity. GALMAN-A increased nitric oxide levels by ~33% at a concentration of 250μg/ml, while GALMAN-A:VO2+/VO3+ decreased nitric oxide levels by ~33% at a concentration of 50μg/ml. Furthermore, GALMAN-A increased interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) levels by 5.5 and 2.3 times, respectively, at a concentration of 25μg/ml; at the same concentration, GALMAN-A:VO2+/VO3+ promoted an increase in IL-1β and IL-6 production by 8 and 5.5 times, respectively. However, neither GALMAN-A nor GALMAN-A:VO2+/VO3+ affected tumor necrosis factor alpha (TNF-α) or interleukin-10 (IL-10) levels. Importantly, both GALMAN-A and GALMAN-A:VO2+/VO3+ exhibited leishmanicidal activity on amastigotes of Leishmania (L.) amazonensis, reaching ~60% activity at concentrations of 100 and 25μg/ml, respectively. These results indicate that GALMAN-A is three times more potent and its oxovanadium complex is twelve times more potent than Glucantime (300μg/ml), which is the drug of choice in leishmaniasis treatment. The IC50 value for GALMAN-A:VO2+/VO3+ was 74.4μg/ml (0.58μg/ml of vanadium). Thus, the significant activation of macrophages and the noted leishmanicidal effect demonstrate the need for further studies to clarify the mechanisms of action of these compounds. GALMAN-A at a concentration of 100μg/ml and the GALMAN-A:VO2+/VO3+ complex at a concentration of 25μg/ml, exhibited leishmanicidal activity of ~60% at concentration levels three fold lower for GALMAN-A and twelve fold lower for GALMAN-A:VO2+/VO3+ than Glucantime (300μg/ml). For this reason, these polymers should be researched for the treatment of leishmaniasis. [Display omitted] •Galactomannan (GALMAN-A) and GALMAN-A:VO2+/VO3+ are potent activators of macrophage.•GALMAN-A and GALMAN-A:VO2+/VO3+ showed leishmanicidal activity in vitro.•GALMAN-A and GALMAN-A:VO2+/VO3+ could be classified as BRMs.