{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T08:27:01Z","timestamp":1787387221274,"version":"build-2736575974"},"reference-count":42,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2019,10,4]],"date-time":"2019-10-04T00:00:00Z","timestamp":1570147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science and Technology Major Projects for &quot;Major New Drugs Innovation and Development&quot;","award":["2017ZX09301024"],"award-info":[{"award-number":["2017ZX09301024"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81673618"],"award-info":[{"award-number":["81673618"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background: The production and maturation of interleukin (IL)-1\u03b2, regulated by the NF-\u03baB and NLRP3 signaling pathways, lie at the core of gout. This study aimed to evaluate the antigout effect of Cichorium intybus L. (also known as chicory) in vivo and in vitro. Methods: A gout animal model was established with monosodium urate (MSU) crystal injections. Rats were orally administered with chicory extract or colchicine. Levels of ankle edema, inflammatory activity, and IL-1\u03b2 release were observed. Several essential targets of the NF-\u03baB and NLRP3 signaling pathways were detected. Primary macrophages were isolated to verify the antigout mechanism of chicory extract as well as chicoric acid in vitro. Results: Improvements of swelling degree, inflammatory activity, and histopathological lesion in MSU-injected ankles were observed in the treatment with chicory extract. Further, the chicory extract significantly decreased IL-1\u03b2 release by suppressing the NF-\u03baB and NLRP3 signaling pathways in gout rats. Similar to the in vivo results, IL-1\u03b2 release was also inhibited by chicory extract and chicoric acid, a specific effective compound in chicory, through the NF-\u03baB and NLRP3 signaling pathways. Conclusion: This study suggests that chicory extract and chicoric acid may be used as promising therapeutic agents against gout by inhibiting the NF-\u03baB and NLRP3 signaling pathways.<\/jats:p>","DOI":"10.3390\/ijms20194921","type":"journal-article","created":{"date-parts":[[2019,10,4]],"date-time":"2019-10-04T10:54:58Z","timestamp":1570186498000},"page":"4921","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Cichorium intybus L. Extract Suppresses Experimental Gout by Inhibiting the NF-\u03baB and NLRP3 Signaling Pathways"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2265-3742","authenticated-orcid":false,"given":"Yu","family":"Wang","sequence":"first","affiliation":[{"name":"School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijian","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuoxi","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanfan","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s12325-014-0175-z","article-title":"A review of uric acid, crystal deposition disease, and gout","volume":"32","author":"Dalbeth","year":"2015","journal-title":"Adv. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1730","DOI":"10.1002\/acr.22648","article-title":"Physical Function, Hyperuricemia, and Gout in Older Adults","volume":"67","author":"Burke","year":"2015","journal-title":"Arthritis Care Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.semarthrit.2015.02.004","article-title":"The economic burden of gout: A systematic review","volume":"45","author":"Rai","year":"2015","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/s13075-015-0610-9","article-title":"Gout and risk of chronic kidney disease and nephrolithiasis: meta-analysis of observational studies","volume":"17","author":"Roughley","year":"2015","journal-title":"Arthritis Res. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1093\/rheumatology\/kep364","article-title":"Gout: an independent risk factor for all-cause and cardiovascular mortality","volume":"49","author":"Kuo","year":"2010","journal-title":"Rheumatology."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1136\/annrheumdis-2016-210588","article-title":"The unclosing premature mortality gap in gout: a general population-based study","volume":"76","author":"Fisher","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"ii2","DOI":"10.1093\/rheumatology\/kep086","article-title":"New insights into the epidemiology of gout","volume":"48","author":"Doherty","year":"2009","journal-title":"Rheumatology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.semarthrit.2016.08.006","article-title":"The rising prevalence and incidence of gout in British Columbia, Canada: Population-based trends from 2000 to 2012","volume":"46","author":"Rai","year":"2017","journal-title":"Semin Arthritis Rheum."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1136\/annrheumdis-2013-204463","article-title":"Rising burden of gout in the UK but continuing suboptimal management: a nationwide population study","volume":"74","author":"Kuo","year":"2015","journal-title":"Ann. Rheum. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"R28","DOI":"10.1186\/ar2143","article-title":"A pilot study of IL-1 inhibition by anakinra in acute gout","volume":"9","author":"So","year":"2007","journal-title":"Arthritis Res. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"52797","DOI":"10.1074\/jbc.M403823200","article-title":"Signaling events involved in macrophage chemokine expression in response to monosodium urate crystals","volume":"279","author":"Jaramillo","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1038\/icb.2014.5","article-title":"Caspases and inflammasomes in metabolic inflammation","volume":"92","author":"Skeldon","year":"2014","journal-title":"Immunol. Cell Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"415","DOI":"10.2165\/00063030-200013060-00005","article-title":"Optimisation of the Treatment of Acute Gout","volume":"13","author":"Mielgo","year":"2000","journal-title":"Biodrugs."},{"key":"ref_14","first-page":"513","article-title":"A double-blind randomized controlled trial appraising the symptom-modifying effects of colchicine on osteoarthritis of the knee","volume":"29","author":"Aran","year":"2011","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"18","DOI":"10.5414\/CN109212","article-title":"Drug-induced kidney injury: A large case series from the Berlin Case-Control Surveillance Study","volume":"89","author":"Douros","year":"2018","journal-title":"Clin Nephrol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Zhong, H., Zhong, Z., Li, H., Zhou, T., and Xie, W. (2018). A rare case report of heavy dose colchicine induced acute kidney injury. BMC Pharmacol Toxicol., 19.","DOI":"10.1186\/s40360-018-0260-z"},{"key":"ref_17","first-page":"1060","article-title":"Studies on Industrial Importance and Medicinal Value of Chicory Plant (Cichorium intybus L.)","volume":"4","author":"Subhash","year":"2016","journal-title":"Int. J. Adv. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1096\/fj.201601071R","article-title":"Chicoric acid supplementation prevents systemic inflammation-induced memory impairment and amyloidogenesis via inhibition of NF-\u03baB","volume":"31","author":"Liu","year":"2017","journal-title":"Faseb J."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"El-Sayed, Y.S., Lebda, M.A., and Mohammed, H. (2015). Neoman, S.A. Chicory (Cichorium intybus L.) Root Extract Regulates the Oxidative Status and Antioxidant Gene Transcripts in CCl4-Induced Hepatotoxicity. PLOS ONE, 10.","DOI":"10.1371\/journal.pone.0121549"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1007\/s10298-008-0313-3","article-title":"Aper\u00e7u ethnobotanique et phytopharmacologique sur Cichorium intybus L.","volume":"6","author":"Rammal","year":"2008","journal-title":"Phytotherapie."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1016\/j.fct.2006.12.019","article-title":"Toxicological evaluation of a chicory root extract","volume":"45","author":"Schmidt","year":"2007","journal-title":"Food Chem. Toxicol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"9455","DOI":"10.3390\/molecules20059455","article-title":"Relationship between High-Performance Liquid Chromatography Fingerprints and Uric Acid-Lowering Activities of Cichorium intybus L.","volume":"20","author":"Zhu","year":"2015","journal-title":"Molecules"},{"key":"ref_23","first-page":"3818","article-title":"Molecular docking analysis of xanthine oxidase inhibition by constituents of cichory","volume":"40","author":"Wang","year":"2015","journal-title":"China J. Chin. Mater. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1764212","DOI":"10.1155\/2018\/1764212","article-title":"Effects of Chicory on Serum Uric Acid, Renal Function, and GLUT9 Expression in Hyperuricaemic Rats with Renal Injury and In Vitro Verification with Cells","volume":"2018","author":"Jin","year":"2018","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s12986-017-0190-6","article-title":"Cichorium intybus L. promotes intestinal uric acid excretion by modulating ABCG2 in experimental hyperuricemia","volume":"14","author":"Wang","year":"2017","journal-title":"Nutr. Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.aca.2015.03.047","article-title":"Preparation and application of molecularly imprinted polymer for isolation of chicoric acid from Chicorium intybus L. medical plant","volume":"877","author":"Saad","year":"2015","journal-title":"Anal. Chim. Acta."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"44","DOI":"10.4103\/0257-7941.150780","article-title":"Anti-inflammatory activity of roots of Cichorium intybus due to its inhibitory effect on various cytokines and antioxidant activity","volume":"34","author":"Rizvi","year":"2014","journal-title":"Anc. Sci. Life."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"29600","DOI":"10.18632\/oncotarget.16768","article-title":"Chicoric acid is a potent anti-atherosclerotic ingredient by anti-oxidant action and anti-inflammation capacity","volume":"8","author":"Tsai","year":"2017","journal-title":"Oncotarget"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"54","DOI":"10.7861\/clinmedicine.17-1-54","article-title":"Gout - a guide for the general and acute physicians","volume":"17","author":"Abhishek","year":"2017","journal-title":"Clin Med"},{"key":"ref_30","first-page":"301","article-title":"Trends in Hyperuricemia and Gout Prevalence: Nutrition and Health Survey in Taiwan from 1993-1996 to 2005-2008","volume":"20","author":"Chuang","year":"2011","journal-title":"Asia Pac. J Clin. Nutr."},{"key":"ref_31","first-page":"410","article-title":"Burden of gout in the Nordic region, 1990\u20132015: findings from the Global Burden of Disease Study 2015. Scand","volume":"47","author":"Kiadaliri","year":"2018","journal-title":"J Rheumatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"574","DOI":"10.3899\/jrheum.170806","article-title":"The Rising Incidence of Gout and the Increasing Burden of Comorbidities: A Population-based Study over 20 Years","volume":"45","author":"Elfishawi","year":"2018","journal-title":"J Rheumatol."},{"key":"ref_33","first-page":"25","article-title":"Febuxostat: the evidence for its use in the treatment of hyperuricaemia and gout","volume":"4","author":"Gaffo","year":"2009","journal-title":"Core Evid."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1111\/j.0105-2896.2009.00860.x","article-title":"Mechanisms of uric acid crystal-mediated autoinflammation","volume":"233","author":"Martinon","year":"2010","journal-title":"Immunol. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1038\/icb.2009.98","article-title":"Crystal-induced neutrophil activation","volume":"88","author":"Naccache","year":"2010","journal-title":"Immunolo Cell Biol."},{"key":"ref_36","first-page":"S410","article-title":"Placebo-controlled study of rilonacept for gout flare prophylaxis during intiation of urate-lowering therapy","volume":"60","author":"Schumacher","year":"2009","journal-title":"Ann. Rheum. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3185","DOI":"10.1182\/blood-2012-05-432104","article-title":"Selective inhibition of the NLRP3 inflammasome by targeting to promyelocytic leukemia protein in mouse and human","volume":"121","author":"Lo","year":"2013","journal-title":"Blood."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.it.2011.01.003","article-title":"Inflammasome activation and IL-1beta and IL-18 processing during infection","volume":"32","author":"Netea","year":"2011","journal-title":"Trends Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1093\/rheumatology\/keh640","article-title":"Mechanisms of inflammation in gout","volume":"44","author":"Busso","year":"2005","journal-title":"Rheumatology."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3213","DOI":"10.4049\/jimmunol.138.10.3213","article-title":"Interleukin 1 (IL 1) as a mediator of crystal arthritis. Stimulation of T cell and synovial fi broblast mitogenesis by urate crystal-induced IL 1","volume":"138","author":"Malawista","year":"1987","journal-title":"J Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/0304-3959(87)90072-8","article-title":"Ankle joint urate arthritis (AJUA) in rats: an alternative animal model of arthritis to that produced by Freund\u2019s adjuvant","volume":"28","author":"Coderre","year":"1987","journal-title":"Pain."},{"key":"ref_42","unstructured":"Zhang, X., Goncalves, R., and Mosser, D.M. (2008). Current Protocols in Immunology, John Wiley & Sons, Inc.. [1st ed.]."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/19\/4921\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:27:33Z","timestamp":1760189253000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/19\/4921"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,4]]},"references-count":42,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2019,10]]}},"alternative-id":["ijms20194921"],"URL":"https:\/\/doi.org\/10.3390\/ijms20194921","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,4]]}}}