## 2 Results and Discussion
### Effect of Curcumin on NO Production of \(L\). infintum-Infected Macrophages
\begin{table}
\begin{tabular}{l c c c} \hline \hline  & \multicolumn{2}{c}{**L. _amazonensis_**} & \multicolumn{2}{c}{_L. infantum_} \\ \cline{2-3}  & \(\mathbf{IC_{50}\)\(\pm\) SE [**] [**g/mL**]} & **SI** & \(\mathbf{IC_{50}\)\(\pm\) SE [**] [**g/mL**]} & **SI** \\ \hline HEXCURC & 102.3 \(\pm\) 7.6 \({}^{\text{a}}\) & 0.47 & 69.6 \(\pm\) 0.2 \({}^{\text{a}}\) & 0.7 \\ DCCURC & 59.6 \(\pm\) 10.3 \({}^{\text{a,b}}\) & 0.9 & 28.2 \(\pm\) 1.5 \({}^{\text{b}}\) & 1.95 \\ ETOHCURC & 53.3 \(\pm\) 9.9 \({}^{\text{b,c}}\) & 1.3 & 74.7 \(\pm\) 1.4 \({}^{\text{a}}\) & 0.94 \\ Curcumin (**1**) & 5.5 \(\pm\) 0.45 \({}^{\text{d}}\) & 12.7 & 15.5 \(\pm\) 1.7 \({}^{\text{c}}\) & 4.5 \\ PAT & 11.9 \(\pm\) 3.1 \({}^{\text{c,d}}\) & 2.6 & \textless{6.25} & \textgreater{4.9} \\ \hline \hline \end{tabular} Results are expressed as the mean values \(\pm\) standard error from three independent experiments. Means with different superscript letters within a column indicate significant differences (One-way ANOVA, Tukey post hoc test, \(p<0.05\)). HEXCURC: \(C\). _longa_ hexane extract; DCCURC: C. _longa_ dichloromethane extract; ETOHCURC: \(C\). _long_ ethanol extract; PAT: potassium antimony(III) tartrate hydrate, as a source of trivalent antimony (5b(III)), reference drug control.  
\end{table} 
Table 4: Assessment of \(C\). _longa_ extracts and **1** anti-promastigotes activity and selectivity indexes (SI) based on macrophages (RAW 264.7) and parasite ratio (CC\({}_{50}\)/IC\({}_{50}\)). sional treatment with curcumin nanoemulsion significantly reduced the parasite burden in _L. major-_infected mice after four weeks of treatment [64]. The variability in results reported in the literature on the antileishmanial effects of curcumin may be attributed to several factors, such as the varying sensitivity among pathogenic species of the _Leishmania_ genus [53], differences in tested concentrations, treatment duration, parasite load, and the solvent of choice to solubilize curcumin, which has included DMSO [63; 26], sodium hydroxide solutions or acetone [60], or in nanoformulations [64]. The results presented here highlight curcumin as a potential candidate to expand the therapeutic arsenal against visceral leishmaniasis caused by _L. infantum_. The investigation of the mechanisms of action of leishmaniasisicidal agents is important for developing new multi-target strategies against leishmaniasisiasis, aiming to overcome the current challenges of conventional treatments. In addition to the favorable results with **1**, the inhibition of _Li_ARG by the turmerone-rich extract (HEXCURC) highlights the inhibitory potential of these sesquiterpenes on the enzyme, suggesting a possible antileishmanial mechanism of action. This is supported by in silico molecular docking assays, which showed that all major compounds from _C. longa_ formed favorable complexes with _Li_ARG, with turmerones displaying a particularly advantageous orientation within the enzyme's active site. These findings underscore the promising potential of sesquiterpenes in targeting _Leishmania_ spp. arginase.