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

  • Planta Med. 2022 Oct;88(13):1123-1131. doi: 10.1055/a-1676-4371.
Diego Pinto de Oliveira  1 ,  Eliana de Faria Garcia  1 ,  Mariana Assíria de Oliveira  1 ,  Luiza C M Candido  2 ,  Fernanda M Coelho  2 ,  Vivian Vasconcelos Costa  2 ,  Nathália Vieira Batista  3 ,  Celso Martins Queiroz-Junior  3 ,  Larissa Froede Brito  4 ,  Lirlândia Pires Sousa  4 ,  Daniele G Souza  2 ,  Flávio Almeida Amaral  3 ,  Rodrigo Maia de Pádua  1 ,  Mauro Martins Teixeira  3 ,  Fernão Castro Braga  1
Affiliations
  • 1. Department of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
  • 2. Department of Microbiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
  • 3. Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
  • 4. Department of Clinical and Toxicological Analyses, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
PMID: 34763354 DOI: 10.1055/a-1676-4371
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.

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