## 1 Introduction  
_Leishmania_ spp. (Trypanosomatidae) are medically significant protozoa that cause a wide range of clinical manifestations collectively known as leishmaniasis. Infections caused by these parasites can lead to ulcerated lesions on the skin and mucous membranes, as tegumetary leishmaniasis, or they can affect internal organs, resulting in visceral leishmaniasisiasis [1]. The treatment of choice, primarily based on pentavalent antimonials, amphoteric B, and miltefosine, depends on several factors such as the parasite species involved and the patient's immune status. Despite the therapeutic arsenal, the drugs do not provide a sterile cure, and the disease can reemerge specially in cases of immunosuppression [2]. Additionally, current treatments face several challenges, including the emergence of resistant parasite strains, high toxicity, variable efficacy, and high rates of treatment abandonment [3; 4]. In this scenario, identifying new drug candidates that target key metabolic pathways in parasites may represent a strong strategy for more efficiently combating leishmaniasisiasis.  
Arginase has emerged as a significant therapeutic target against leishmaniasis. The hydrolysis of L-arginine by arginase is the first step in the biosynthesis of polyamines, cationic molecules fundamental for transmembrane transport and parasite differentiation. Additionally, polyamines participate in the synthesis of trypanothione, which plays a protective role against reactive oxygen species (ROS) that can induce parasite death [5]. Host cells, particularly macrophages, also express the enzyme, but this is not considered an issue since arginase competes with inducible nitric oxide synthase (iNOS) for the L-arginine substrate. Inhibiting host cell arginase may therefore enhance their microbicidal activity by increasing the availability of L-arginine for iNOS [6]. Several anti-_Leishmania_ agents have demonstrated inhibitory activity against _Leishmania_ arginase, with flavonoids being the most extensively studied [7; 8; 9; 10]. Additionally, cinnamic acid derivatives [10; 11], chalcones [12], phenylhydrazides [13], fucogalactan [14], and benzimidazole [15] have also exhibited inhibitory effects.  
_Curcuna longa_ (Zingiberaceae), native to Southeast Asia, has been widely distributed across the world, particularly in tropical and subtropical regions [16]. The rhizome of _C. longa_ is traditionally used as a food ingredient for its distinctive flavor and digestive properties [17]. Extracts from _C. longa_ and its major components, especially curcuminoids and turmerones, have been extensively studied as bioactive agents against various illnesses, including leishmaniasis. These chemical classes have served as starting points for synthesizing new compound analogues [18; 19], developing nanoformulations [20; 21], exploring combination therapies [22; 23], and employing photodynamic therapy [24; 25], all showing great potential for disease control. Previously described mechanisms of action include apoptosis induction, the increased production of reactive oxygen species (ROS), mitochondrial dysfunction, the disruption of calcium homeostasis, the depletion of trypanothione, and enzymatic inhibition [18; 20; 26; 27].  
In the present study, we describe a novel mode of action of curcuminoids and turmerone-rich extracts from _C. longa_ against _Leishmania_. The hexane, dichloromethane, and ethanol extracts and the main component curcumin inhibited _L. infattum_ recombinant arginase (_Li_ARG) in addition to killing the parasite. In silico analysis revealed that other curcuminoids and turmerones present in the fractions are also capable of binding to the enzyme. These findings provide a new mode of action of _C. longa_ main compounds, especially curcumin, against _Leishman_ parasites.