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Therefore, herein, we investigated the potential of E. purpurea aqueous extracts (AEs) obtained from flowers (F), leaves (L), or roots (R) as an immune booster in human primary monocyte\u2010derived macrophages (hMDMs). Additionally, to identify the main class of compounds (phenolic\/carboxylic acids vs. alkylamides) responsible for the bioactivity, the three AEs were fractioned by semi-preparative high-performance liquid chromatography (HPLC). The AEs and the isolated phenolic\/carboxylic acidic fractions were not cytotoxic for hMDMs for all tested concentrations, as confirmed by the metabolic activity and DNA content assays. Moreover, AE drastically induced the production of the interleukin (IL)-6 and tumor necrosis factor (TNF)-\u03b1, with a minimal effect on IL-1\u03b2 and prostaglandin E2 (PGE2), supporting their potential for macrophage activation. Interestingly, in the presence\n          of the phenolic\/carboxylic acidic fractions, this efficacy considerably decreased, suggesting a complementary effect between compounds. AE also triggered the phosphorylation of the extracellular signal-regulated kinase (ERK) 1\/2 and p38 signaling pathways and upregulated the cyclooxygenase (COX)-2 expression in hMDMs. Overall, AE-F was demonstrated to be the most powerful immunostimulant extract that can be related to their higher number in identified bioactive compounds compared to AE-L and AE-R. These results highlight the efficiency of E. purpurea AE to enhance the function of a key cell type of the immune system and their potential as immunostimulant formulations for patients with a compromised immune system due to certain diseases (e.g., acquired immunodeficiencies) and treatments (e.g., chemotherapy).<\/jats:p>","DOI":"10.1055\/a-2436-9664","type":"journal-article","created":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T22:43:07Z","timestamp":1729204987000},"page":"1143-1155","source":"Crossref","is-referenced-by-count":4,"title":["Evaluation of Echinacea purpurea Extracts as Immunostimulants: Impact on Macrophage Activation"],"prefix":"10.1055","volume":"90","author":[{"given":"Sara F.","family":"Vieira","sequence":"additional","affiliation":[{"name":"3B\u02bcs Research Group, I3BS \u2013 Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimar\u00e3es, Portugal"},{"name":"ICVS\/3B\u02bcs\u2013PT Government Associate Laboratory, Braga\/Guimar\u00e3es, Portugal"}]},{"given":"Samuel M.","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"ICVS\/3B\u02bcs\u2013PT Government Associate Laboratory, Braga\/Guimar\u00e3es, Portugal"},{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal"}]},{"given":"Virg\u00ednia M. F.","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"TOXRUN \u2013 Toxicology Research Unit, University Institute of Health Sciences, CESPU, Gandra, Portugal"},{"name":"UNIPRO \u2013 Oral Pathology and Rehabilitation Research Unit, University Institute of Health Sciences (IUCS), CESPU, Gandra, Portugal"}]},{"given":"Maria E.","family":"Tiritan","sequence":"additional","affiliation":[{"name":"TOXRUN \u2013 Toxicology Research Unit, University Institute of Health Sciences, CESPU, Gandra, Portugal"},{"name":"Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), University of Porto, 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, Porto, Portugal"}]},{"given":"Cristina","family":"Cunha","sequence":"additional","affiliation":[{"name":"ICVS\/3B\u02bcs\u2013PT Government Associate Laboratory, Braga\/Guimar\u00e3es, Portugal"},{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal"}]},{"given":"Agostinho","family":"Carvalho","sequence":"additional","affiliation":[{"name":"ICVS\/3B\u02bcs\u2013PT Government Associate Laboratory, Braga\/Guimar\u00e3es, Portugal"},{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal"}]},{"given":"Rui L.","family":"Reis","sequence":"additional","affiliation":[{"name":"3B\u02bcs Research Group, I3BS \u2013 Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimar\u00e3es, Portugal"},{"name":"ICVS\/3B\u02bcs\u2013PT Government Associate Laboratory, Braga\/Guimar\u00e3es, Portugal"}]},{"given":"Helena","family":"Ferreira","sequence":"additional","affiliation":[{"name":"3B\u02bcs Research Group, I3BS \u2013 Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimar\u00e3es, Portugal"},{"name":"ICVS\/3B\u02bcs\u2013PT Government Associate Laboratory, 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\u02bcs Research Group, I3BS \u2013 Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimar\u00e3es, Portugal"},{"name":"ICVS\/3B\u02bcs\u2013PT Government Associate Laboratory, Braga\/Guimar\u00e3es, Portugal"}]}],"member":"194","published-online":{"date-parts":[[2024,10,17]]},"reference":[{"key":"ref1","volume-title":"WHO Monographs on 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