Spíndola Flora F S, Pinheiro Anderson S, Mpalantinos Maria Athana, Silva Jefferson R A, Neto Walter S M F, Conceição Raissa A, Barreto Eduarda M, Abrahim-Vieira Barbara A, Rodrigues Carlos R, Souza Alessandra M T, Nico Dirlei, Amaral Ana Claudia F, Garcia Andreza R, Rodrigues Igor A
Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil.
Departamento de Bioquímica, Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil.
Pharmaceuticals (Basel). 2025 Jun 6;18(6):851. doi: 10.3390/ph18060851.
: The anti- potential of and its derivatives, such as curcuminoids, is well-established, yet their mechanisms of action remain underexplored. This study investigates the inhibitory effects of extracts and curcumin on arginase, a key enzyme in polyamine and trypanothione biosynthesis, and evaluates their antiparasitic activity. : Extracts were prepared via rhizome successive maceration with hexane (HEXCURC), dichloromethane (DCCURC), and ethanol (ETOHCURC) and chemically characterized by a combination of chromatographic and spectrometric methods. The inhibition of recombinant arginase (ARG) was assessed by urea quantification, while molecular docking explored interactions between the main compounds annotated in the extracts and the enzyme's active site. Biological activity was tested against promastigotes, intracellular amastigotes, and mammalian cells. : LC-MS and GC-MS revealed curcuminoids and turmerones as main compounds annotated in the extracts. DCCURC, HEXCURC, and curcumin showed the strongest ARG inhibition (IC = 10.04, 14.4, and 17.55 μg/mL, respectively). Docking analysis revealed that curcumin, demethoxycurcumin, and bisdemethoxycurcumin bind near the active site, with binding energies of -3.43, -4.14, and -3.99 kcal/mol, respectively. Curcumin demonstrated superior anti-promastigote activity (IC = 15.01 μg/mL) and selectivity (SI = 12.7) compared to the extracts. It also significantly reduced amastigote burden in infected macrophages (IC = 13.6 μg/mL). : This is the first report demonstrating that extracts and curcumin inhibit ARG. These findings support curcumin's potential as a lead compound for developing multi-target therapies against leishmaniasis, combining enzyme inhibition with direct antiparasitic effects.
姜黄及其衍生物（如姜黄素类化合物）的抗寄生虫潜力已得到充分证实，但其作用机制仍有待深入研究。本研究调查了姜黄提取物和姜黄素对精氨酸酶的抑制作用，精氨酸酶是多胺和锥虫硫醇生物合成中的关键酶，并评估了它们的抗寄生虫活性。提取物通过用己烷（HEXCURC）、二氯甲烷（DCCURC）和乙醇（ETOHCURC）对根茎进行连续浸渍制备，并通过色谱和光谱方法相结合进行化学表征。通过尿素定量评估重组利什曼原虫精氨酸酶（ARG）的抑制作用，同时分子对接探索提取物中注释的主要化合物与酶活性位点之间的相互作用。针对前鞭毛体、细胞内无鞭毛体和哺乳动物细胞测试了生物活性。LC-MS和GC-MS显示姜黄素类化合物和姜黄酮是提取物中注释的主要化合物。DCCURC、HEXCURC和姜黄素显示出最强的ARG抑制作用（IC50分别为10.04、14.4和17.55μg/mL）。对接分析表明，姜黄素、去甲氧基姜黄素和双去甲氧基姜黄素结合在活性位点附近，结合能分别为-3.43、-4.14和-3.99kcal/mol。与提取物相比，姜黄素表现出优异的抗前鞭毛体活性（IC50 = 15.01μg/mL）和选择性（SI = 12.7）。它还显著降低了感染巨噬细胞中的无鞭毛体负荷（IC50 = 13.6μg/mL）。这是第一份证明姜黄提取物和姜黄素抑制ARG的报告。这些发现支持姜黄素作为开发针对利什曼病的多靶点疗法的先导化合物的潜力，将酶抑制与直接抗寄生虫作用相结合。
