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The Biological Activity of Natural Alkaloids against Herbivores, Cancerous Cells and Pathogens
Open AccessArticle

Curine Inhibits Macrophage Activation and Neutrophil Recruitment in a Mouse Model of Lipopolysaccharide-Induced Inflammation

Laboratório de Investigação em Genética e Hematologia Translacional, Instituto Gonçalo Moniz, FIOCRUZ, Salvador 40296-710, Brazil
Laboratório de Imunofarmacologia, Departamento de Fisiologia e Patologia, UFPB, João Pessoa 58051-900, Brazil
Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro 21040-360, Brazil
Laboratório de Fitoquímica, Departamento de Ciências Farmacêuticas, UFPB, João Pessoa 58051-900, Brazil
Author to whom correspondence should be addressed.
Toxins 2019, 11(12), 705;
Received: 18 September 2019 / Revised: 20 October 2019 / Accepted: 22 October 2019 / Published: 3 December 2019
(This article belongs to the Special Issue Biological Activities of Alkaloids: From Toxicology to Pharmacology)
Curine is a bisbenzylisoquinoline alkaloid (BBA) with anti-allergic, analgesic, and anti-inflammatory properties. Previous studies have demonstrated that this alkaloid is orally active at non-toxic doses. However, the mechanisms underlying its anti-inflammatory effects remain to be elucidated. This work aimed to investigate the effects of curine on macrophage activation and neutrophil recruitment. Using a murine model of lipopolysaccharide (LPS)-induced pleurisy, we demonstrated that curine significantly inhibited the recruitment of neutrophils in association with the inhibition of cytokines tumor necrosis factor (TNF-α), interleukin (IL)-1β, IL-6, monocyte chemotactic protein (CCL2/MCP-1) as well as leukotriene B4 in the pleural lavage of mice. Curine treatment reduced cytokine levels and the expression of iNOS in in vitro cultures of macrophages stimulated with LPS. Treatment with a calcium channel blocker resulted in comparable inhibition of TNF-α and IL-1β production, as well as iNOS expression by macrophages, suggesting that the anti-inflammatory effects of curine may be related to the inhibition of calcium-dependent mechanisms involved in macrophage activation. In conclusion, curine presented anti-inflammatory effects that are associated with inhibition of macrophage activation and neutrophil recruitment by inhibiting the production of inflammatory cytokines, LTB4 and nitric oxide (NO), and possibly by negatively modulating Ca2+ influx. View Full-Text
Keywords: Curine; alkaloid; macrophage; neutrophil; lipopolysaccharide Curine; alkaloid; macrophage; neutrophil; lipopolysaccharide
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Ribeiro-Filho, J.; Carvalho Leite, F.; Surrage Calheiros, A.; de Brito Carneiro, A.; Alves Azeredo, J.; Fernandes de Assis, E.; da Silva Dias, C.; Regina Piuvezam, M.; T. Bozza, P. Curine Inhibits Macrophage Activation and Neutrophil Recruitment in a Mouse Model of Lipopolysaccharide-Induced Inflammation. Toxins 2019, 11, 705.

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