{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T04:10:39Z","timestamp":1778127039299,"version":"3.51.4"},"reference-count":63,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T00:00:00Z","timestamp":1675900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"FCT","doi-asserted-by":"publisher","award":["PD\/BD\/135246\/2017"],"award-info":[{"award-number":["PD\/BD\/135246\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT","doi-asserted-by":"publisher","award":["COVID\/BD\/152012\/2021"],"award-info":[{"award-number":["COVID\/BD\/152012\/2021"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT","doi-asserted-by":"publisher","award":["SFRH\/BD\/136814\/2018"],"award-info":[{"award-number":["SFRH\/BD\/136814\/2018"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT","doi-asserted-by":"publisher","award":["CEECIND\/04058\/2018"],"award-info":[{"award-number":["CEECIND\/04058\/2018"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT","doi-asserted-by":"publisher","award":["PD\/00169\/2013"],"award-info":[{"award-number":["PD\/00169\/2013"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT","doi-asserted-by":"publisher","award":["NORTE-01-0145-FEDER-000039"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000039"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT","doi-asserted-by":"publisher","award":["NORTE-01-0145-FEDER-000021"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000021"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"HEALTH-UNORTE","award":["PD\/BD\/135246\/2017"],"award-info":[{"award-number":["PD\/BD\/135246\/2017"]}]},{"name":"HEALTH-UNORTE","award":["COVID\/BD\/152012\/2021"],"award-info":[{"award-number":["COVID\/BD\/152012\/2021"]}]},{"name":"HEALTH-UNORTE","award":["SFRH\/BD\/136814\/2018"],"award-info":[{"award-number":["SFRH\/BD\/136814\/2018"]}]},{"name":"HEALTH-UNORTE","award":["CEECIND\/04058\/2018"],"award-info":[{"award-number":["CEECIND\/04058\/2018"]}]},{"name":"HEALTH-UNORTE","award":["PD\/00169\/2013"],"award-info":[{"award-number":["PD\/00169\/2013"]}]},{"name":"HEALTH-UNORTE","award":["NORTE-01-0145-FEDER-000039"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000039"]}]},{"name":"HEALTH-UNORTE","award":["NORTE-01-0145-FEDER-000021"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000021"]}]},{"name":"Norte2020","award":["PD\/BD\/135246\/2017"],"award-info":[{"award-number":["PD\/BD\/135246\/2017"]}]},{"name":"Norte2020","award":["COVID\/BD\/152012\/2021"],"award-info":[{"award-number":["COVID\/BD\/152012\/2021"]}]},{"name":"Norte2020","award":["SFRH\/BD\/136814\/2018"],"award-info":[{"award-number":["SFRH\/BD\/136814\/2018"]}]},{"name":"Norte2020","award":["CEECIND\/04058\/2018"],"award-info":[{"award-number":["CEECIND\/04058\/2018"]}]},{"name":"Norte2020","award":["PD\/00169\/2013"],"award-info":[{"award-number":["PD\/00169\/2013"]}]},{"name":"Norte2020","award":["NORTE-01-0145-FEDER-000039"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000039"]}]},{"name":"Norte2020","award":["NORTE-01-0145-FEDER-000021"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Echinacea purpurea is traditionally used in the treatment of inflammatory diseases. Therefore, we investigated the anti-inflammatory capacity of E. purpurea dichloromethanolic (DE) and ethanolic extracts obtained from flowers and roots (R). To identify the class of compounds responsible for the strongest bioactivity, the extracts were fractionated into phenol\/carboxylic acid (F1) and alkylamide fraction (F2). The chemical fingerprint of bioactive compounds in the fractions was evaluated by LC-HRMS. E. purpurea extracts and fractions significantly reduced pro-inflammatory cytokines (interleukin 6 and\/or tumor necrosis factor) and reactive oxygen and nitrogen species (ROS\/RNS) production by lipopolysaccharide-stimulated primary human monocyte-derived macrophages. Dichloromethanolic extract obtained from roots (DE-R) demonstrated the strongest anti-inflammatory activity. Moreover, fractions exhibited greater anti-inflammatory activity than whole extract. Indeed, alkylamides must be the main compounds responsible for the anti-inflammatory activity of extracts; thus, the fractions presenting high content of these compounds presented greater bioactivity. It was demonstrated that alkylamides exert their anti-inflammatory activity through the downregulation of the phosphorylation of p38, ERK 1\/2, STAT 3, and\/or NF-\u03baB signaling pathways, and\/or downregulation of cyclooxygenase 2 expression. E. purpurea extracts and fractions, mainly DE-R-F2, are promising and powerful plant-based anti-inflammatory formulations that can be further used as a basis for the treatment of inflammatory diseases.<\/jats:p>","DOI":"10.3390\/antiox12020425","type":"journal-article","created":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T02:56:13Z","timestamp":1675997773000},"page":"425","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Echinacea purpurea Fractions Represent Promising Plant-Based Anti-Inflammatory Formulations"],"prefix":"10.3390","volume":"12","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\u2013PT Government Associate Laboratory, Braga, Guimar\u00e3es, Portugal"}]},{"given":"Samuel M.","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"ICVS\/3B\u2019s\u2013PT Government Associate Laboratory, Braga, Guimar\u00e3es, Portugal"},{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, 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, 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, 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"}]},{"given":"Cristina","family":"Cunha","sequence":"additional","affiliation":[{"name":"ICVS\/3B\u2019s\u2013PT Government Associate Laboratory, Braga, Guimar\u00e3es, Portugal"},{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8935-8030","authenticated-orcid":false,"given":"Agostinho","family":"Carvalho","sequence":"additional","affiliation":[{"name":"ICVS\/3B\u2019s\u2013PT Government Associate Laboratory, Braga, Guimar\u00e3es, Portugal"},{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, 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\u2013PT Government Associate Laboratory, 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\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\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\u2013PT Government Associate Laboratory, Braga, Guimar\u00e3es, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1038\/s41591-019-0675-0","article-title":"Chronic inflammation in the etiology of disease across the life span","volume":"25","author":"Furman","year":"2019","journal-title":"Nat. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/j.cell.2010.03.006","article-title":"Inflammation 2010: New adventures of an old flame","volume":"140","author":"Medzhitov","year":"2010","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1038\/nri910","article-title":"NF-kappaB regulation in the immune system","volume":"2","author":"Li","year":"2002","journal-title":"Nat. Rev. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/nri3495","article-title":"Mitogen-activated protein kinases in innate immunity","volume":"13","author":"Arthur","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/nri3859","article-title":"Eicosanoid storm in infection and inflammation","volume":"15","author":"Dennis","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/ni.3153","article-title":"IL-6 as a keystone cytokine in health and disease","volume":"16","author":"Hunter","year":"2015","journal-title":"Nat. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/nrd.2016.39","article-title":"Resolution of inflammation: A new therapeutic frontier","volume":"15","author":"Fullerton","year":"2016","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Hirayama, D., Iida, T., and Nakase, H. (2017). The Phagocytic Function of Macrophage-Enforcing Innate Immunity and Tissue Homeostasis. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19010092"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1089\/ars.2012.5149","article-title":"Reactive oxygen species in inflammation and tissue injury","volume":"20","author":"Mittal","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/S0899-9007(96)00000-8","article-title":"Inflammation, free radicals, and antioxidants","volume":"12","author":"Conner","year":"1996","journal-title":"Nutrition"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2563","DOI":"10.1016\/j.bbamcr.2014.05.014","article-title":"Cytokines and chemokines: At the crossroads of cell signalling and inflammatory disease","volume":"1843","author":"Turner","year":"2014","journal-title":"Biochim. Biophys. Acta-Mol. Cell Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"18001","DOI":"10.1038\/nrdp.2018.1","article-title":"Rheumatoid arthritis","volume":"4","author":"Smolen","year":"2018","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1038\/s41584-022-00749-9","article-title":"Synovial inflammation in osteoarthritis progression","volume":"18","author":"Coras","year":"2022","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1186\/ar116","article-title":"Pharmacological basis for the therapy of pain and inflammation with nonsteroidal anti-inflammatory drugs","volume":"2","author":"Steinmeyer","year":"2000","journal-title":"Arthritis Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/sj.bjp.0706736","article-title":"How corticosteroids control inflammation: Quintiles prize lecture 2005","volume":"148","author":"Barnes","year":"2006","journal-title":"Br. J. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"279","DOI":"10.3389\/fphar.2019.00279","article-title":"Biological therapies in immune-mediated inflammatory diseases: Can biosimilars reduce access inequities?","volume":"10","author":"Baumgart","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"14534","DOI":"10.1038\/s41598-019-51067-2","article-title":"NSAIDs disrupt intestinal homeostasis by suppressing macroautophagy in intestinal epithelial cells","volume":"9","author":"Bryan","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1111\/apt.15097","article-title":"Review article: Managing the adverse events caused by anti-TNF therapy in inflammatory bowel disease","volume":"49","author":"Shivaji","year":"2019","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1021\/acs.jnatprod.9b01285","article-title":"Natural products as sources of new drugs over the nearly four decades from 01\/1981 to 09\/2019","volume":"83","author":"Newman","year":"2020","journal-title":"J. Nat. Prod."},{"key":"ref_20","unstructured":"WHO (1999). WHO Monographs on Selected Medicinal Plants-Volume 1, World Health Organization."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1093\/ecam\/neh118","article-title":"Echinacea: A miracle herb against aging and cancer? Evidence in vivo in mice","volume":"2","author":"Miller","year":"2005","journal-title":"Evid. Based. Complement. Alternat. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.3390\/plants11091244","article-title":"Echinacea purpurea (L.) Moench: Biological and Pharmacological Properties. A Review","volume":"11","author":"Jurca","year":"2022","journal-title":"Plants"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.jep.2015.09.007","article-title":"Echinacea complex\u2013chemical view and anti-asthmatic profile","volume":"175","author":"Capek","year":"2015","journal-title":"J. Ethnopharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1039\/C6RA25901D","article-title":"Cichoric acid regulates the hepatic glucose homeostasis via AMPK pathway and activates the antioxidant response in high glucose-induced hepatocyte injury","volume":"7","author":"Zhu","year":"2017","journal-title":"RSC Adv."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1021\/jm0509039","article-title":"Immuno-suppressive effect of blocking the CD28 signaling pathway in T-cells by an active component of Echinacea found by a novel pharmaceutical screening method","volume":"49","author":"Dong","year":"2006","journal-title":"J. Med. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.jep.2017.10.012","article-title":"Mast cell degranulation and calcium influx are inhibited by an Echinacea purpurea extract and the alkylamide dodeca-2E,4E-dienoic acid isobutylamide","volume":"212","author":"Gulledge","year":"2018","journal-title":"J. Ethnopharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/j.jnutbio.2009.08.010","article-title":"Comparative metabolomics approach coupled with cell- and gene-based assays for species classification and anti-inflammatory bioactivity validation of Echinacea plants","volume":"21","author":"Hou","year":"2010","journal-title":"J. Nutr. Biochem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1016\/j.intimp.2006.02.003","article-title":"Echinacea alkylamides inhibit interleukin-2 production by Jurkat T cells","volume":"6","author":"Sasagawa","year":"2006","journal-title":"Int. Immunopharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1021\/np040245f","article-title":"Macrophage activating effects of new alkamides from the roots of Echinacea species","volume":"68","author":"Chen","year":"2005","journal-title":"J. Nat. Prod."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"14192","DOI":"10.1074\/jbc.M601074200","article-title":"Alkylamides from Echinacea are a new class of cannabinomimetics. Cannabinoid type 2 receptor-dependent and -independent immunomodulatory effects","volume":"281","author":"Raduner","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"11966","DOI":"10.1021\/jf202958r","article-title":"Echinacea alkamides prevent lipopolysaccharide\/D-galactosamine-induced acute hepatic injury through JNK pathway-mediated HO-1 expression","volume":"59","author":"Hou","year":"2011","journal-title":"J. Agric. Food Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"106974","DOI":"10.1016\/j.intimp.2020.106974","article-title":"Echinacea polysaccharide alleviates LPS-induced lung injury via inhibiting inflammation, apoptosis and activation of the TLR4\/NF-\u03baB signal pathway","volume":"88","author":"Zhang","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.cellimm.2015.07.003","article-title":"Echinacea purpurea root extract inhibits TNF release in response to Pam3Csk4 in a phosphatidylinositol-3-kinase dependent manner","volume":"297","author":"Fast","year":"2015","journal-title":"Cell. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.ijbiomac.2021.07.095","article-title":"Echinacea purpurea polysaccharide prepared by fractional precipitation prevents alcoholic liver injury in mice by protecting the intestinal barrier and regulating liver-related pathways","volume":"187","author":"Jiang","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"7576","DOI":"10.1039\/D0FO01367F","article-title":"Post-screening characterization of an acidic polysaccharide from Echinacea purpurea with potent anti-inflammatory properties in vivo","volume":"11","author":"Li","year":"2020","journal-title":"Food Funct."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.ijbiomac.2020.01.129","article-title":"Polysaccharide from Echinacea purpurea reduce the oxidant stress in vitro and in vivo","volume":"149","author":"Hou","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.fct.2017.06.041","article-title":"Cichoric acid improved hyperglycaemia and restored muscle injury via activating antioxidant response in MLD-STZ-induced diabetic mice","volume":"107","author":"Zhu","year":"2017","journal-title":"Food Chem. Toxicol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1007\/s11095-008-9754-5","article-title":"Blocking effect of an immuno-suppressive agent, cynarin, on CD28 of T-cell receptor","volume":"26","author":"Dong","year":"2009","journal-title":"Pharm. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"112503","DOI":"10.1016\/j.phytochem.2020.112503","article-title":"Sesquiterpenes from Echinacea purpurea and their anti-inflammatory activities","volume":"179","author":"Cheng","year":"2020","journal-title":"Phytochemistry"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.jep.2008.11.028","article-title":"Echinacea increases arginase activity and has anti-inflammatory properties in RAW 264.7 macrophage cells, indicative of alternative macrophage activation","volume":"122","author":"Zhai","year":"2009","journal-title":"J. Ethnopharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/j.intimp.2009.03.006","article-title":"Synergistic immunomopharmacological effects of N-alkylamides in Echinacea purpurea herbal extracts","volume":"9","author":"Chicca","year":"2009","journal-title":"Int. Immunopharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Vieira, S.F., Gon\u00e7alves, V.M.F., Llaguno, C.P., Mac\u00edas, F., Tiritan, M.E., Reis, R.L., Ferreira, H., and Neves, N.M. (2022). On the Bioactivity of Echinacea purpurea Extracts to Modulate the Production of Inflammatory Mediators. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232113616"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Vieira, S.F., Ferreira, H., and Neves, N.M. (2020). Antioxidant and anti-Inflammatory activities of cytocompatible Salvia officinalis extracts: A comparison between traditional and soxhlet extraction. Antioxidants, 9.","DOI":"10.3390\/antiox9111157"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"10425","DOI":"10.1021\/jf2025677","article-title":"Chromatographic methods for metabolite profiling of virus- and phytoplasma-infected plants of Echinacea purpurea","volume":"59","author":"Pellati","year":"2011","journal-title":"J. Agric. Food Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.chroma.2005.11.008","article-title":"High performance liquid chromatography\/electrospray ionization mass spectrometry for simultaneous analysis of alkamides and caffeic acid derivatives from Echinacea purpurea extracts","volume":"1103","author":"Cech","year":"2006","journal-title":"J. Chromatogr. A"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1016\/j.jpba.2009.02.011","article-title":"Comparison of alkylamide yield in ethanolic extracts prepared from fresh versus dry Echinacea purpurea utilizing HPLC\u2013ESI-MS","volume":"49","author":"Spelman","year":"2009","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"12131","DOI":"10.1021\/jf303292t","article-title":"Seasonal variations in the concentrations of lipophilic compounds and phenolic acids in the roots of Echinacea purpurea and Echinacea pallida","volume":"60","author":"Thomsen","year":"2012","journal-title":"J. Agric. Food Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/S0021-9673(98)00447-6","article-title":"Analysis of alkamides in roots and achenes of Echinacea purpurea by liquid chromatography\u2013electrospray mass spectrometry","volume":"815","author":"He","year":"1998","journal-title":"J. Chromatogr. A"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"8086","DOI":"10.1021\/jf201158k","article-title":"Analysis of alkylamides in Echinacea plant materials and dietary supplements by ultrafast liquid chromatography with diode array and mass spectrometric detection","volume":"59","author":"Mudge","year":"2011","journal-title":"J. Agric. Food Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1055\/s-2006-962030","article-title":"TLC and HPLC analysis of alkamides in Echinacea drugs","volume":"55","author":"Bauer","year":"1989","journal-title":"Planta Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2282","DOI":"10.1038\/s41467-020-16120-z","article-title":"Phagosomal removal of fungal melanin reprograms macrophage metabolism to promote antifungal immunity","volume":"11","author":"Campos","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"478","DOI":"10.3389\/fimmu.2013.00478","article-title":"TNF receptor 2 and disease: Autoimmunity and regenerative medicine","volume":"4","author":"Faustman","year":"2013","journal-title":"Front. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/S0731-7085(03)00645-9","article-title":"Analysis of phenolic compounds and radical scavenging activity of Echinacea spp","volume":"35","author":"Pellati","year":"2004","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.lwt.2011.09.026","article-title":"Caffeic acid derivatives, total phenols, antioxidant and antimutagenic activities of Echinacea purpurea flower extracts","volume":"46","author":"Tsai","year":"2012","journal-title":"LWT-Food Sci. Technol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.redox.2015.09.005","article-title":"Reactive oxygen species and mitochondria: A nexus of cellular homeostasis","volume":"6","author":"Alvarez","year":"2015","journal-title":"Redox Biol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Zeeshan, H.M.A., Lee, G.H., Kim, H.-R., and Chae, H.-J. (2016). Endoplasmic Reticulum Stress and Associated ROS. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17030327"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1016\/j.bbadis.2011.12.001","article-title":"Role of peroxisomes in ROS\/RNS-metabolism: Implications for human disease","volume":"1822","author":"Fransen","year":"2012","journal-title":"Biochim. Biophys. Acta-Mol. Basis Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1098\/rstb.1985.0164","article-title":"Biological antioxidants","volume":"311","author":"Burton","year":"1985","journal-title":"Philos. Trans. R. Soc. London. B Biol. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S1532-0456(02)00271-5","article-title":"The generation of free radicals by nitric oxide synthase","volume":"134","author":"Porasuphatana","year":"2003","journal-title":"Comp. Biochem. Physiol. Part C Toxicol. Pharmacol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1080\/08820130600745786","article-title":"Alkylamides from echinacea modulate induced immune responses in macrophages","volume":"36","author":"Matthias","year":"2007","journal-title":"Immunol. Investig."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.febslet.2004.10.064","article-title":"Echinacea alkylamides modulate TNF-alpha gene expression via cannabinoid receptor CB2 and multiple signal transduction pathways","volume":"577","author":"Gertsch","year":"2004","journal-title":"FEBS Lett."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"20725","DOI":"10.1007\/s11356-020-08557-y","article-title":"Chicoric acid prevents methotrexate hepatotoxicity via attenuation of oxidative stress and inflammation and up-regulation of PPAR\u03b3 and Nrf2\/HO-1 signaling","volume":"27","author":"Hussein","year":"2020","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1007\/s00011-019-01241-z","article-title":"Chicoric acid prevents methotrexate-induced kidney injury by suppressing NF-\u03baB\/NLRP3 inflammasome activation and up-regulating Nrf2\/ARE\/HO-1 signaling","volume":"68","author":"Hussein","year":"2019","journal-title":"Inflamm. Res."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/12\/2\/425\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:28:22Z","timestamp":1760120902000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/12\/2\/425"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,9]]},"references-count":63,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["antiox12020425"],"URL":"https:\/\/doi.org\/10.3390\/antiox12020425","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,9]]}}}