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diseases are the focus of several clinical studies, due to limitations and serious side effects of available therapies. Plant-based drugs (e.g., salicylic acid, morphine) have become landmarks in the pharmaceutical field. Therefore, we investigated the immunomodulatory effects of flowers, leaves, and roots from Echinacea purpurea. Ethanolic (EE) and dichloromethanolic extracts (DE) were obtained using the Accelerated Solvent Extractor and aqueous extracts (AE) were prepared under stirring. Their chemical fingerprint was evaluated by liquid chromatography\u2013high resolution mass spectrometry (LC-HRMS). The pro- and anti-inflammatory effects, as well as the reduction in intracellular reactive oxygen and nitrogen species (ROS\/RNS), of the different extracts were evaluated using non-stimulated and lipopolysaccharide-stimulated macrophages. Interestingly, AE were able to stimulate macrophages to produce pro-inflammatory cytokines (tumor necrosis factor -TNF-\u03b1, interleukin -IL-1\u03b2, and IL-6), and to generate ROS\/RNS. Conversely, under an inflammatory scenario, all extracts reduced the amount of pro-inflammatory mediators. DE, alkylamides-enriched extracts, showed the strongest anti-inflammatory activity. Moreover, E. purpurea extracts demonstrated generally a more robust anti-inflammatory activity than clinically used anti-inflammatory drugs (dexamethasone, diclofenac, salicylic acid, and celecoxib). Therefore, E. purpurea extracts may be used to develop new effective therapeutic formulations for disorders in which the immune system is either overactive or impaired.<\/jats:p>","DOI":"10.3390\/ijms232113616","type":"journal-article","created":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T11:56:36Z","timestamp":1667908596000},"page":"13616","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["On the Bioactivity of Echinacea purpurea Extracts to Modulate the Production of Inflammatory Mediators"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9158-3114","authenticated-orcid":false,"given":"Sara F.","family":"Vieira","sequence":"first","affiliation":[{"name":"3B\u2019s Research Group, I3Bs\u2014Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ci\u00eancia e Tecnologia, Zona Industrial da Gandra, Barco, 4805-017 Guimar\u00e3es, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, 4710-057 Braga\/Guimar\u00e3es, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9151-516X","authenticated-orcid":false,"given":"Virg\u00ednia M. F.","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"TOXRUN\u2014Toxicology Research Unit, University Institute of Health Sciences (IUCS), CESPU, CRL, 4585-116 Gandra, Portugal"},{"name":"UNIPRO\u2014Oral Pathology and Rehabilitation Research Unit, University Institute of Health Sciences (IUCS), CESPU, CRL, 4585-116 Gandra, Portugal"}]},{"given":"Carmen P.","family":"Llaguno","sequence":"additional","affiliation":[{"name":"Departamento de Edafolox\u00eda e Qu\u00edmica Agr\u00edcola, Facultade de Biolox\u00eda, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain"}]},{"given":"Felipe","family":"Mac\u00edas","sequence":"additional","affiliation":[{"name":"Departamento de Edafolox\u00eda e Qu\u00edmica Agr\u00edcola, Facultade de Biolox\u00eda, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3320-730X","authenticated-orcid":false,"given":"Maria Elizabeth","family":"Tiritan","sequence":"additional","affiliation":[{"name":"TOXRUN\u2014Toxicology Research Unit, University Institute of Health Sciences (IUCS), CESPU, CRL, 4585-116 Gandra, Portugal"},{"name":"Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es, Avenida General Norton de Matos, S\/N, 4450-208 Matosinhos, Portugal"},{"name":"Laborat\u00f3rio de Qu\u00edmica Org\u00e2nica e Farmac\u00eautica, Departamento de Ci\u00eancias Qu\u00edmicas, Faculdade de Farm\u00e1cia da Universidade do Porto, Rua Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4295-6129","authenticated-orcid":false,"given":"Rui L.","family":"Reis","sequence":"additional","affiliation":[{"name":"3B\u2019s Research Group, I3Bs\u2014Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ci\u00eancia e Tecnologia, Zona Industrial da Gandra, Barco, 4805-017 Guimar\u00e3es, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, 4710-057 Braga\/Guimar\u00e3es, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3770-9393","authenticated-orcid":false,"given":"Helena","family":"Ferreira","sequence":"additional","affiliation":[{"name":"3B\u2019s Research Group, I3Bs\u2014Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ci\u00eancia e Tecnologia, Zona Industrial da Gandra, Barco, 4805-017 Guimar\u00e3es, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, 4710-057 Braga\/Guimar\u00e3es, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3041-0687","authenticated-orcid":false,"given":"Nuno M.","family":"Neves","sequence":"additional","affiliation":[{"name":"3B\u2019s Research Group, I3Bs\u2014Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ci\u00eancia e Tecnologia, Zona Industrial da Gandra, Barco, 4805-017 Guimar\u00e3es, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, 4710-057 Braga\/Guimar\u00e3es, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1038\/nature07201","article-title":"Origin and physiological roles of inflammation","volume":"454","author":"Medzhitov","year":"2008","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1084\/jem.185.9.1661","article-title":"Lipopolysaccharide (LPS)-induced macrophage activation and signal transduction in the absence of Src-family kinases Hck, Fgr, and Lyn","volume":"185","author":"Meng","year":"1997","journal-title":"J. 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