Curcumin as a Stabilizer of Macrophage Polarization during <i>Plasmodium</i> Infection

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...

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Main Authors: Maria Clara C. Cordeiro, Fernanda D. Tomé, Felipe S. Arruda, Simone Gonçalves da Fonseca, Patrícia R. A. Nagib, Mara R. N. Celes
Format: Article
Language:English
Published: MDPI AG 2023-10-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/15/10/2505
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author Maria Clara C. Cordeiro
Fernanda D. Tomé
Felipe S. Arruda
Simone Gonçalves da Fonseca
Patrícia R. A. Nagib
Mara R. N. Celes
author_facet Maria Clara C. Cordeiro
Fernanda D. Tomé
Felipe S. Arruda
Simone Gonçalves da Fonseca
Patrícia R. A. Nagib
Mara R. N. Celes
author_sort Maria Clara C. Cordeiro
collection DOAJ
description 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 <i>Plasmodium berghei</i> 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.
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spelling doaj.art-d337201c6f7541569d16d453dedd90002023-11-19T17:45:28ZengMDPI AGPharmaceutics1999-49232023-10-011510250510.3390/pharmaceutics15102505Curcumin as a Stabilizer of Macrophage Polarization during <i>Plasmodium</i> InfectionMaria Clara C. Cordeiro0Fernanda D. Tomé1Felipe S. Arruda2Simone Gonçalves da Fonseca3Patrícia R. A. Nagib4Mara R. N. Celes5Department of Bioscience and Technology, Institute of Tropical Pathology and Public Health, Federal University of Goiás, Goiânia 74605-050, GO, BrazilDepartment of Bioscience and Technology, Institute of Tropical Pathology and Public Health, Federal University of Goiás, Goiânia 74605-050, GO, BrazilDepartment of Bioscience and Technology, Institute of Tropical Pathology and Public Health, Federal University of Goiás, Goiânia 74605-050, GO, BrazilDepartment of Bioscience and Technology, Institute of Tropical Pathology and Public Health, Federal University of Goiás, Goiânia 74605-050, GO, BrazilDepartment of Microbiology, Immunology and Parasitology, Biological Science Institute, Federal University of Juiz de Fora, Juiz de Fora 36036-900, MG, BrazilDepartment of Bioscience and Technology, Institute of Tropical Pathology and Public Health, Federal University of Goiás, Goiânia 74605-050, GO, BrazilMalaria 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 <i>Plasmodium berghei</i> 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.https://www.mdpi.com/1999-4923/15/10/2505RAW 264.7 cellscurcuminmalariaiNOSarginasephagocytosis
spellingShingle Maria Clara C. Cordeiro
Fernanda D. Tomé
Felipe S. Arruda
Simone Gonçalves da Fonseca
Patrícia R. A. Nagib
Mara R. N. Celes
Curcumin as a Stabilizer of Macrophage Polarization during <i>Plasmodium</i> Infection
Pharmaceutics
RAW 264.7 cells
curcumin
malaria
iNOS
arginase
phagocytosis
title Curcumin as a Stabilizer of Macrophage Polarization during <i>Plasmodium</i> Infection
title_full Curcumin as a Stabilizer of Macrophage Polarization during <i>Plasmodium</i> Infection
title_fullStr Curcumin as a Stabilizer of Macrophage Polarization during <i>Plasmodium</i> Infection
title_full_unstemmed Curcumin as a Stabilizer of Macrophage Polarization during <i>Plasmodium</i> Infection
title_short Curcumin as a Stabilizer of Macrophage Polarization during <i>Plasmodium</i> Infection
title_sort curcumin as a stabilizer of macrophage polarization during i plasmodium i infection
topic RAW 264.7 cells
curcumin
malaria
iNOS
arginase
phagocytosis
url https://www.mdpi.com/1999-4923/15/10/2505
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