Nootkatone Inhibits Acute and Chronic Inflammatory Responses in Mice

  • Molecules. 2020 May 7;25(9):2181. doi: 10.3390/molecules25092181.
Lindaiane Bezerra Rodrigues Dantas  1 ,  Ana Letícia Moreira Silva  1 ,  Cícero Pedro da Silva Júnior  2 ,  Isabel Sousa Alcântara  2 ,  Maria Rayane Correia de Oliveira  2 ,  Anita Oliveira Brito Pereira Bezerra Martins  2 ,  Jaime Ribeiro-Filho  3 ,  Henrique Douglas Melo Coutinho  4 ,  Fabíolla Rocha Santos Passos  5 ,  Lucindo José Quintans-Junior  5 ,  Irwin Rose Alencar de Menezes  2 ,  Raffaele Pezzani  6  7 ,  Sara Vitalini  8
Affiliations
  • 1. Departamento de Saúde, Centro Universitário Dr. Leão Sampaio-UNILEÃO, Av. Leão Sampaio, 400-Lagoa Seca, Juazeiro do Norte 63040-000, Ceará, Brazil.
  • 2. Laboratory of Pharmacology and Molecular Chemistry, Department of Biological Chemistry, Regional University of Cariri, Rua Coronel Antônio Luis 1161, Pimenta, Crato 63105-000, Ceará, Brazil.
  • 3. Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador 45500-000, Bahia, Brazil.
  • 4. Microbiology and Biology Molecular Laboratory, Department of Chemical Biology, Regional University of Cariri, Crato 63105-000, Ceara, Brazil.
  • 5. Graduate Program in Health Sciences, Federal University of Sergipe, Aracaju, Sergipe 49100-000, Brazil.
  • 6. O.U. Endocrinology, Department of Medicine (DIMED), University of Padova, via Ospedale 105, 35128 Padova, Italy.
  • 7. AIROB, Associazione Italiana per la Ricerca Oncologica di Base, 35128 Padova, Italy.
  • 8. Department of Agricultural and Environmental Sciences, Milan State University, via G. Celoria 2, 20133 Milan, Italy.
PMID: 32392744 DOI: 10.3390/molecules25092181
Abstract

Nootkatone (NTK) is a sesquiterpenoid found in essential oils of many species of Citrus (Rutaceae). Considering previous reports demonstrating that NTK inhibited inflammatory signaling pathways, this study aimed to investigate the effects of this compound in mice models of acute and chronic inflammation. Murine models of paw edema induced by carrageenan, dextran, histamine, and arachidonic acid, as well as carrageenan-induced peritonitis and pleurisy, were used to evaluate the effects of NTK on acute inflammation. A murine model of granuloma induced by cotton pellets was used to access the impact of NTK treatment on chronic inflammation. In the acute inflammation models, NTK demonstrated antiedematogenic effects and inhibited leukocyte recruitment, which was associated with decreased vascular permeability, inhibition of myeloperoxidase (MPO), interleukin (IL)1-β, and tumor necrosis factor (TNF)-α production. In silico analysis suggest that NTZ anti-inflammatory effects may also occur due to inhibition of cyclooxygenase (COX)-2 activity and antagonism of the Histamine Receptor type 1 (H1). These mechanisms might have contributed to the reduction of granuloma weight and protein concentration in the homogenates, observed in the chronic inflammation model. In conclusion, NTK exerted anti-inflammatory effects that are associated with inhibition of IL1-β and TNF-α production, possibly due to inhibition of COX-2 activity and antagonism of the H1 receptor. However, further studies are required to characterize the effects of this compound on chronic inflammation.

Keywords
acute inflammation; anti-inflammatory; granuloma; nootkatone.
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