{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T07:16:29Z","timestamp":1792653389174,"version":"4.5.0"},"reference-count":29,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,5,7]],"date-time":"2020-05-07T00:00:00Z","timestamp":1588809600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["304291\/2017-0"],"award-info":[{"award-number":["304291\/2017-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>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-\u03b2, and tumor necrosis factor (TNF)-\u03b1 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-\u03b2 and TNF-\u03b1 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.<\/jats:p>","DOI":"10.3390\/molecules25092181","type":"journal-article","created":{"date-parts":[[2020,5,8]],"date-time":"2020-05-08T03:45:20Z","timestamp":1588909520000},"page":"2181","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Nootkatone Inhibits Acute and Chronic Inflammatory Responses in Mice"],"prefix":"10.3390","volume":"25","author":[{"given":"Lindaiane","family":"Bezerra Rodrigues Dantas","sequence":"first","affiliation":[{"name":"Departamento de Sa\u00fade, Centro Universit\u00e1rio Dr. Le\u00e3o Sampaio-UNILE\u00c3O, Av. Le\u00e3o Sampaio, 400-Lagoa Seca, Juazeiro do Norte 63040-000, Cear\u00e1, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Let\u00edcia Moreira","family":"Silva","sequence":"additional","affiliation":[{"name":"Departamento de Sa\u00fade, Centro Universit\u00e1rio Dr. Le\u00e3o Sampaio-UNILE\u00c3O, Av. Le\u00e3o Sampaio, 400-Lagoa Seca, Juazeiro do Norte 63040-000, Cear\u00e1, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00edcero Pedro","family":"da Silva J\u00fanior","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology and Molecular Chemistry, Department of Biological Chemistry, Regional University of Cariri, Rua Coronel Ant\u00f4nio Luis 1161, Pimenta, Crato 63105-000, Cear\u00e1, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2537-0134","authenticated-orcid":false,"given":"Isabel Sousa","family":"Alc\u00e2ntara","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology and Molecular Chemistry, Department of Biological Chemistry, Regional University of Cariri, Rua Coronel Ant\u00f4nio Luis 1161, Pimenta, Crato 63105-000, Cear\u00e1, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2568-0519","authenticated-orcid":false,"given":"Maria Rayane","family":"Correia de Oliveira","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology and Molecular Chemistry, Department of Biological Chemistry, Regional University of Cariri, Rua Coronel Ant\u00f4nio Luis 1161, Pimenta, Crato 63105-000, Cear\u00e1, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Oliveira Brito Pereira Bezerra Martins","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology and Molecular Chemistry, Department of Biological Chemistry, Regional University of Cariri, Rua Coronel Ant\u00f4nio Luis 1161, Pimenta, Crato 63105-000, Cear\u00e1, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3126-6509","authenticated-orcid":false,"given":"Jaime","family":"Ribeiro-Filho","sequence":"additional","affiliation":[{"name":"Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation, Salvador 45500-000, Bahia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6634-4207","authenticated-orcid":false,"given":"Henrique Douglas Melo","family":"Coutinho","sequence":"additional","affiliation":[{"name":"Microbiology and Biology Molecular Laboratory, Department of Chemical Biology, Regional University of Cariri, Crato 63105-000, Ceara, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fab\u00edolla","family":"Rocha Santos Passos","sequence":"additional","affiliation":[{"name":"Graduate Program in Health Sciences, Federal University of Sergipe, Aracaju, Sergipe 49100-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5155-938X","authenticated-orcid":false,"given":"Lucindo Jos\u00e9","family":"Quintans-Junior","sequence":"additional","affiliation":[{"name":"Graduate Program in Health Sciences, Federal University of Sergipe, Aracaju, Sergipe 49100-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1065-9581","authenticated-orcid":false,"given":"Irwin Rose","family":"Alencar de Menezes","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology and Molecular Chemistry, Department of Biological Chemistry, Regional University of Cariri, Rua Coronel Ant\u00f4nio Luis 1161, Pimenta, Crato 63105-000, Cear\u00e1, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3156-2500","authenticated-orcid":false,"given":"Raffaele","family":"Pezzani","sequence":"additional","affiliation":[{"name":"O.U. Endocrinology, Department of Medicine (DIMED), University of Padova, via Ospedale 105, 35128 Padova, Italy"},{"name":"AIROB, Associazione Italiana per la Ricerca Oncologica di Base, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7557-9473","authenticated-orcid":false,"given":"Sara","family":"Vitalini","sequence":"additional","affiliation":[{"name":"Department of Agricultural and Environmental Sciences, Milan State University, via G. Celoria 2, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.immuni.2014.02.009","article-title":"Proresolving lipid mediators and mechanisms in the resolution of acute inflammation","volume":"40","author":"Buckley","year":"2014","journal-title":"Immunity"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1007\/s00441-017-2753-2","article-title":"Partners in crime: Neutrophils and monocytes\/macrophages in inflammation and disease","volume":"371","author":"Nicholls","year":"2018","journal-title":"Cell Tissue Res."},{"key":"ref_3","unstructured":"Hannoodee, S., and Nasuruddin, D.N. (2020). 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