Cordeiro Maria Clara C, Tomé Fernanda D, Arruda Felipe S, da Fonseca Simone Gonçalves, Nagib Patrícia R A, Celes Mara R N
Department of Bioscience and Technology, Institute of Tropical Pathology and Public Health, Federal University of Goiás, Goiânia 74605-050, GO, Brazil.
Department of Microbiology, Immunology and Parasitology, Biological Science Institute, Federal University of Juiz de Fora, Juiz de Fora 36036-900, MG, Brazil.
Pharmaceutics. 2023 Oct 21;15(10):2505. doi: 10.3390/pharmaceutics15102505.
Malaria is a parasitic infection responsible for high morbidity and mortality rates worldwide. During the disease, phagocytosis of infected red blood cells by the macrophages induces the production of reactive oxygen (ROS) and nitrogen species (RNS), culminating in parasite death. Curcumin (CUR) is a bioactive compound that has been demonstrated to reduce the production of pro-inflammatory cytokines and chemokines produced by macrophages but to reduce parasitemia in infected mice. Hence, the main purpose of this study is to investigate whether curcumin may interfere with macrophage function and polarization after infection in vitro. In our findings, non-polarized macrophage (M0), classically activated (M1), and alternatively activated (M2) phenotypes showed significantly increased phagocytosis of infected red blood cells (iRBCs) when compared to phagocytosis of uninfected red blood cells (RBCs) 3 h after infection. After 24 h, M1 macrophages exposed to RBCs + CUR showed greater elimination capacity when compared to macrophages exposed to iRBCs + CUR, suggesting the interference of curcumin with the microbicidal activity. Additionally, curcumin increased the phagocytic activity of macrophages when used in non-inflammatory conditions (M0) and reduced the inducible nitric oxide synthase (iNOS) and arginase activities in all macrophage phenotypes infected (M0, M1, and M2), suggesting interference in arginine availability by curcumin and balance promotion in macrophage polarization in neutral phenotype (M0). These results support the view of curcumin treatment in malaria as an adjuvant, promoting a balance between pro- and anti-inflammatory responses for a better clinical outcome.
疟疾是一种寄生虫感染，在全球范围内导致高发病率和死亡率。在疾病过程中，巨噬细胞对受感染红细胞的吞噬作用会诱导活性氧（ROS）和活性氮（RNS）的产生，最终导致寄生虫死亡。姜黄素（CUR）是一种生物活性化合物，已被证明可减少巨噬细胞产生的促炎细胞因子和趋化因子，但可降低感染小鼠的寄生虫血症。因此，本研究的主要目的是调查姜黄素在体外感染后是否可能干扰巨噬细胞功能和极化。在我们的研究结果中，与感染后3小时未感染红细胞（RBC）的吞噬作用相比，未极化巨噬细胞（M0）、经典激活（M1）和交替激活（M2）表型对感染红细胞（iRBC）的吞噬作用显著增加。24小时后，与暴露于iRBC + CUR的巨噬细胞相比，暴露于RBC + CUR的M1巨噬细胞显示出更大的清除能力，这表明姜黄素对杀菌活性有干扰作用。此外，姜黄素在非炎症条件下（M0）使用时可增加巨噬细胞的吞噬活性，并降低所有感染的巨噬细胞表型（M0、M1和M2）中的诱导型一氧化氮合酶（iNOS）和精氨酸酶活性，这表明姜黄素对精氨酸可用性有干扰作用，并促进中性表型（M0）巨噬细胞极化的平衡。这些结果支持将姜黄素治疗疟疾作为一种佐剂的观点，促进促炎和抗炎反应之间的平衡以获得更好的临床结果。
