cis-Aconitic Acid, a Constituent of Echinodorus grandiflorus Leaves, Inhibits Antigen-Induced Arthritis and Gout in Mice

Diego Pinto de Oliveira; Eliana de Faria Garcia; Mariana Assíria de Oliveira; Luiza C. M. Candido; Fernanda M. Coelho; Vivian Vasconcelos Costa; Nathália Vieira Batista; Celso Martins Queiroz-Junior; Larissa Froede Brito; Lirlândia Pires Sousa; Daniele G. Souza; Flávio Almeida Amaral; Rodrigo Maia de Pádua; Mauro Martins Teixeira; Fernão Castro Braga

doi:10.1055/a-1676-4371

Planta Medica, Table of Contents

Planta Med 2022; 88(13): 1123-1131
DOI: 10.1055/a-1676-4371

Biological and Pharmacological Activity

Original Papers

cis-Aconitic Acid, a Constituent of Echinodorus grandiflorus Leaves, Inhibits Antigen-Induced Arthritis and Gout in Mice

Diego Pinto de Oliveira

¹Department of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

,

Eliana de Faria Garcia

¹Department of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

,

Mariana Assíria de Oliveira

¹Department of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

,

Luiza C. M. Candido

²Department of Microbiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

,

Fernanda M. Coelho

²Department of Microbiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

,

Vivian Vasconcelos Costa

²Department of Microbiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

,

Nathália Vieira Batista

³Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

,

Celso Martins Queiroz-Junior

³Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

,

Larissa Froede Brito

⁴Department of Clinical and Toxicological Analyses, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

,

Lirlândia Pires Sousa

⁴Department of Clinical and Toxicological Analyses, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

,

Daniele G. Souza

²Department of Microbiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

,

Flávio Almeida Amaral

³Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

,

Rodrigo Maia de Pádua

¹Department of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

,

Mauro Martins Teixeira

³Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

,

Fernão Castro Braga

¹Department of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

› Author Affiliations

Abstract

cis-Aconitic acid is a constituent from the leaves of Echinodorus grandiflorus, a medicinal plant traditionally used in Brazil to treat inflammatory conditions, including arthritic diseases. The present study aimed to investigate the anti-arthritic effect of cis-aconitic acid in murine models of antigen-induced arthritis and monosodium urate-induced gout. The possible underlying mechanisms of action was evaluated in THP-1 macrophages. Oral treatment with cis-aconitic acid (10, 30, and 90 mg/kg) reduced leukocyte accumulation in the joint cavity and C-X-C motif chemokine ligand 1 and IL-1β levels in periarticular tissue. cis-Aconitic acid treatment reduced joint inflammation in tissue sections of antigen-induced arthritis mice and these effects were associated with decreased mechanical hypernociception. Administration of cis-aconitic acid (30 mg/kg p. o.) also reduced leukocyte accumulation in the joint cavity after the injection of monosodium urate crystals. cis-Aconitic acid reduced in vitro the release of TNF-α and phosphorylation of IκBα in lipopolysaccharide-stimulated THP-1 macrophages, suggesting that inhibition of nuclear factor kappa B activation was an underlying mechanism of cis-aconitic acid-induced anti-inflammatory effects. In conclusion, cis-aconitic acid has significant anti-inflammatory effects in antigen-induced arthritis and monosodium urate-induced arthritis in mice, suggesting its potential for the treatment of inflammatory diseases of the joint in humans. Additionally, our findings suggest that this compound may contribute to the anti-inflammatory effect previously reported for E. grandiflorus extracts.

Key words

cis-aconitic acid - rheumatoid arthritis - gout - complete Freundʼs adjuvant - Echinodorus grandiflorus - Alismataceae - NFκB

Full Text

References

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