{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T06:59:42Z","timestamp":1792738782943,"version":"4.5.0"},"reference-count":48,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T00:00:00Z","timestamp":1600905600000},"content-version":"vor","delay-in-days":267,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:p><jats:italic>Background<\/jats:italic>. Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by sacroiliitis and spinal rigidity of the axial joints. The role of oxidative stress and increased proinflammatory cytokines is well documented in AS pathogenesis. Punicalagin (2,3\u2010hexahydroxydiphenoyl\u2010gallagyl\u2010D\u2010glucose), an ellagitannin widely present in pomegranates, is found to exhibit potent anti\u2010inflammatory, antiproliferative, and antioxidative effects. The present study was undertaken to investigate the effects of punicalagin in a rodent model of AS. <jats:italic>Methods<\/jats:italic>. BALB\/c mice induced spondylitis were sacrificed 24\u2009h after the last injection of proteoglycan extract. Histological scoring was done to assess the degree of the disease. The expression of JAK2\/STAT3 proteins and proteins of the nuclear factor\u2010<jats:italic>\u03ba<\/jats:italic>B (NF\u2010<jats:italic>\u03ba<\/jats:italic>B) pathway was determined by immunoblotting. Serum levels of inflammatory mediators\u2014TNF\u2010<jats:italic>\u03b1<\/jats:italic>, IL\u20101<jats:italic>\u03b2<\/jats:italic>, IL\u20106, IL\u201017A, and IL\u201023\u2014were assessed. Levels of lipid peroxidation and reactive oxygen species (ROS) were quantified. Antioxidant status as a measure of activities of antioxidant enzymes\u2014catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD)\u2014was determined. <jats:italic>Results<\/jats:italic>. Punicalagin effectively improved antioxidant status and decreased lipid peroxidation, ROS production, and serum levels of inflammatory mediators. NF\u2010<jats:italic>\u03ba<\/jats:italic>B pathway and JAK2\/STAT3 signaling were significantly (<jats:italic>p<\/jats:italic> &lt; 0.05) downregulated. Punicalagin effectively regulated the production of cytokines by the Th17 cells and the IL\u201017A\/IL\u201023 axis. <jats:italic>Conclusion<\/jats:italic>. The observations suggest that punicalagin exerts a protective role in AS via reducing oxidative stress and regulating NF\u2010<jats:italic>\u03ba<\/jats:italic>B\/TH17\/JAK2\/STAT3 signal. Punicalagin thus could be explored further as a potent candidate compound in the treatment of AS.<\/jats:p>","DOI":"10.1155\/2020\/4918239","type":"journal-article","created":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T23:32:15Z","timestamp":1600990335000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Punicalagin Exerts Protective Effects against Ankylosing Spondylitis by Regulating NF\u2010<i>\u03ba<\/i>B\u2010TH17\/JAK2\/STAT3 Signaling and Oxidative Stress"],"prefix":"10.1155","volume":"2020","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4176-494X","authenticated-orcid":false,"given":"Xinzhe","family":"Feng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8026-9557","authenticated-orcid":false,"given":"Qinyuan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6003-7011","authenticated-orcid":false,"given":"Chen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0176-9834","authenticated-orcid":false,"given":"Wenwen","family":"Tong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5159-1523","authenticated-orcid":false,"given":"Weidong","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,9,24]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60635-7"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1505066"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11882-014-0489-6"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.05.097"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.907589"},{"key":"e_1_2_10_6_2","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2015-208902"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2017.56"},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2295"},{"key":"e_1_2_10_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.23655"},{"key":"e_1_2_10_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1261"},{"key":"e_1_2_10_11_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI21404"},{"key":"e_1_2_10_12_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-018-0680-z"},{"key":"e_1_2_10_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2013.12.032"},{"key":"e_1_2_10_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2006.03.018"},{"key":"e_1_2_10_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-008-8064-8"},{"key":"e_1_2_10_16_2","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-202698"},{"key":"e_1_2_10_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00754.x"},{"key":"e_1_2_10_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2017.23"},{"key":"e_1_2_10_19_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.11.5699"},{"key":"e_1_2_10_20_2","doi-asserted-by":"publisher","DOI":"10.5152\/eurjrheum.2015.0031"},{"key":"e_1_2_10_21_2","doi-asserted-by":"publisher","DOI":"10.3109\/s10165-009-0230-9"},{"key":"e_1_2_10_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-8981(02)00373-X"},{"key":"e_1_2_10_23_2","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/171573"},{"key":"e_1_2_10_24_2","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2016.3410"},{"key":"e_1_2_10_25_2","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/2673076"},{"key":"e_1_2_10_26_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms151119458"},{"key":"e_1_2_10_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2017.11.030"},{"key":"e_1_2_10_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2017.01.025"},{"key":"e_1_2_10_29_2","doi-asserted-by":"publisher","DOI":"10.1631\/jzus.b1600224"},{"key":"e_1_2_10_30_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00696"},{"key":"e_1_2_10_31_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar4096"},{"key":"e_1_2_10_32_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI23738"},{"key":"e_1_2_10_33_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2004.029710"},{"key":"e_1_2_10_34_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2006.065888"},{"key":"e_1_2_10_35_2","first-page":"1032","article-title":"The influence of illness and variables associated with functional limitations in Chinese patients with ankylosing spondylitis","volume":"34","author":"Tam L. 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