{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T01:23:01Z","timestamp":1772500981201,"version":"3.50.1"},"reference-count":40,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,2,19]],"date-time":"2021-02-19T00:00:00Z","timestamp":1613692800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018537","name":"National Science and Technology Major Project","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018537","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002367","name":"Chinese Academy of Sciences","doi-asserted-by":"publisher","award":["XDA12020231"],"award-info":[{"award-number":["XDA12020231"]}],"id":[{"id":"10.13039\/501100002367","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["18431907100"],"award-info":[{"award-number":["18431907100"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2016YFA0502301"],"award-info":[{"award-number":["2016YFA0502301"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012402","name":"CAS Key Laboratory of Receptor Research","doi-asserted-by":"publisher","award":["SIMM1904YKF-01"],"award-info":[{"award-number":["SIMM1904YKF-01"]}],"id":[{"id":"10.13039\/501100012402","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013279","name":"National Key New Drug Creation and Manufacturing Program, Ministry of Science and Technology","doi-asserted-by":"publisher","award":["2018ZX09711002-006-011"],"award-info":[{"award-number":["2018ZX09711002-006-011"]}],"id":[{"id":"10.13039\/501100013279","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Advanced Research"],"published-print":{"date-parts":[[2021,11]]},"DOI":"10.1016\/j.jare.2021.02.006","type":"journal-article","created":{"date-parts":[[2021,3,7]],"date-time":"2021-03-07T11:05:07Z","timestamp":1615115107000},"page":"241-251","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":23,"special_numbering":"C","title":["Identification of phosphodiesterase-4 as the therapeutic target of arctigenin in alleviating psoriatic skin inflammation"],"prefix":"10.1016","volume":"33","author":[{"given":"Heng","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianglei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caigui","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunlan","family":"Feng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moting","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huimin","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haixia","family":"Su","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Qi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yechun","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.jare.2021.02.006_b0005","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.freeradbiomed.2015.08.008","article-title":"Osthol attenuates neutrophilic oxidative stress and hemorrhagic shock-induced lung injury via inhibition of phosphodiesterase 4","volume":"89","author":"Tsai","year":"2015","journal-title":"Free Radical Biol. Med."},{"key":"10.1016\/j.jare.2021.02.006_b0010","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.freeradbiomed.2017.03.002","article-title":"6-Hydroxy-5,7-dimethoxy-flavone suppresses the neutrophil respiratory burst via selective PDE4 inhibition to ameliorate acute lung injury","volume":"106","author":"Tsai","year":"2017","journal-title":"Free Radical Biol. Med."},{"issue":"35","key":"10.1016\/j.jare.2021.02.006_b0015","doi-asserted-by":"crossref","first-page":"6372","DOI":"10.1039\/C8OB01388H","article-title":"Natural products as modulators of the cyclic-AMP pathway: evaluation and synthesis of lead compounds","volume":"16","author":"Sengupta","year":"2018","journal-title":"Org. Biomol. Chem."},{"issue":"5","key":"10.1016\/j.jare.2021.02.006_b0020","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/aps.2018.32","article-title":"Overview of the anti-inflammatory effects, pharmacokinetic properties and clinical efficacies of arctigenin and arctiin from Arctium lappa L","volume":"39","author":"Gao","year":"2018","journal-title":"Acta Pharmacol. Sin."},{"issue":"6","key":"10.1016\/j.jare.2021.02.006_b0025","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1007\/s10753-018-0856-x","article-title":"Arctiin Prevents LPS-Induced Acute Lung Injury via Inhibition of PI3K\/AKT Signaling Pathway in Mice","volume":"41","author":"Zhou","year":"2018","journal-title":"Inflammation"},{"key":"10.1016\/j.jare.2021.02.006_b0030","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.biopha.2018.03.060","article-title":"Arctigenin protects against liver injury from acute hepatitis by suppressing immune cells in mice","volume":"102","author":"Cheng","year":"2018","journal-title":"Biomed. Pharmacother."},{"issue":"2","key":"10.1016\/j.jare.2021.02.006_b0035","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1007\/s10753-014-9969-z","article-title":"Arctigenin attenuates lipopolysaccharide-induced acute lung injury in rats","volume":"38","author":"Shi","year":"2015","journal-title":"Inflammation"},{"key":"10.1016\/j.jare.2021.02.006_b0040","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.3389\/fimmu.2018.01881","article-title":"Quantitative Proteomic Analysis Reveals That Arctigenin Alleviates Concanavalin A-Induced Hepatitis Through Suppressing Immune System and Regulating Autophagy","volume":"9","author":"Feng","year":"2018","journal-title":"Front. Immunol."},{"issue":"4","key":"10.1016\/j.jare.2021.02.006_b0045","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.bcp.2015.06.008","article-title":"Arctigenin exerts anti-colitis efficacy through inhibiting the differentiation of Th1 and Th17 cells via an mTORC1-dependent pathway","volume":"96","author":"Wu","year":"2015","journal-title":"Biochem. Pharmacol."},{"issue":"2","key":"10.1016\/j.jare.2021.02.006_b0050","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.intimp.2014.09.026","article-title":"Arctigenin but not arctiin acts as the major effective constituent of Arctium lappa L. fruit for attenuating colonic inflammatory response induced by dextran sulfate sodium in mice","volume":"23","author":"Wu","year":"2014","journal-title":"Int. Immunopharmacol."},{"issue":"1\u20133","key":"10.1016\/j.jare.2021.02.006_b0055","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.ejphar.2013.01.014","article-title":"Arctigenin ameliorates inflammation in vitro and in vivo by inhibiting the PI3K\/AKT pathway and polarizing M1 macrophages to M2-like macrophages","volume":"708","author":"Hyam","year":"2013","journal-title":"Eur. J. Pharmacol."},{"issue":"8","key":"10.1016\/j.jare.2021.02.006_b0060","doi-asserted-by":"crossref","first-page":"5356","DOI":"10.1007\/s12035-015-9462-1","article-title":"Arctigenin Suppress Th17 Cells and Ameliorates Experimental Autoimmune Encephalomyelitis Through AMPK and PPAR-gamma\/ROR-gammat Signaling","volume":"53","author":"Li","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"10.1016\/j.jare.2021.02.006_b0065","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mce.2016.11.026","article-title":"Modulation of signaling through GPCR-cAMP-PKA pathways by PDE4 depends on stimulus intensity: Possible implications for the pathogenesis of acrodysostosis without hormone resistance","volume":"442","author":"Motte","year":"2017","journal-title":"Mol. Cell. Endocrinol."},{"issue":"12","key":"10.1016\/j.jare.2021.02.006_b0070","doi-asserted-by":"crossref","first-page":"8082","DOI":"10.4049\/jimmunol.174.12.8082","article-title":"Evidence for a role of phosphodiesterase 4 in lipopolysaccharide-stimulated prostaglandin E2 production and matrix metalloproteinase-9 activity in human amniochorionic membranes","volume":"174","author":"Oger","year":"2005","journal-title":"J. Immunol."},{"issue":"7","key":"10.1016\/j.jare.2021.02.006_b0075","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/j.cellsig.2016.01.007","article-title":"Phosphodiesterase 4 in inflammatory diseases: Effects of apremilast in psoriatic blood and in dermal myofibroblasts through the PDE4\/CD271 complex","volume":"28","author":"Schafer","year":"2016","journal-title":"Cell. Signal."},{"issue":"13","key":"10.1016\/j.jare.2021.02.006_b0080","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1111\/bph.14667","article-title":"Inhibition of phosphodiesterase-4 attenuates murine ulcerative colitis through interference with mucosal immunity","volume":"176","author":"Li","year":"2019","journal-title":"Br. J. Pharmacol."},{"issue":"4","key":"10.1016\/j.jare.2021.02.006_b0085","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/nrd4228","article-title":"Advances in targeting cyclic nucleotide phosphodiesterases","volume":"13","author":"Maurice","year":"2014","journal-title":"Nat. Rev. Drug Discov."},{"issue":"3","key":"10.1016\/j.jare.2021.02.006_b0090","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1038\/bjp.2008.307","article-title":"PDE4 inhibitors: current status","volume":"155","author":"Spina","year":"2008","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.jare.2021.02.006_b0095","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.3389\/fphar.2018.01048","article-title":"Phosphodiesterase-4 Inhibitors for the Treatment of Inflammatory Diseases","volume":"9","author":"Li","year":"2018","journal-title":"Front. Pharmacol."},{"issue":"5","key":"10.1016\/j.jare.2021.02.006_b0100","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/nri3646","article-title":"Mechanisms regulating skin immunity and inflammation","volume":"14","author":"Pasparakis","year":"2014","journal-title":"Nat. Rev. Immunol."},{"issue":"12","key":"10.1016\/j.jare.2021.02.006_b0105","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1038\/ni1275","article-title":"Immune cell migration in inflammation: present and future therapeutic targets","volume":"6","author":"Luster","year":"2005","journal-title":"Nat. Immunol."},{"issue":"9","key":"10.1016\/j.jare.2021.02.006_b0110","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1038\/nri1689","article-title":"Getting under the skin: the immunogenetics of psoriasis","volume":"5","author":"Bowcock","year":"2005","journal-title":"Nat. Rev. Immunol."},{"issue":"6","key":"10.1016\/j.jare.2021.02.006_b0115","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1038\/ni.3742","article-title":"Interleukin 17 is a chief orchestrator of immunity","volume":"18","author":"Veldhoen","year":"2017","journal-title":"Nat. Immunol."},{"issue":"9","key":"10.1016\/j.jare.2021.02.006_b0120","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/nri3707","article-title":"The IL-23-IL-17 immune axis: from mechanisms to therapeutic testing","volume":"14","author":"Gaffen","year":"2014","journal-title":"Nat. Rev. Immunol."},{"issue":"11","key":"10.1016\/j.jare.2021.02.006_b0125","doi-asserted-by":"crossref","first-page":"5579","DOI":"10.1021\/acs.jmedchem.9b00518","article-title":"Structure-Aided Identification and Optimization of Tetrahydro-isoquinolines as Novel PDE4 Inhibitors Leading to Discovery of an Effective Antipsoriasis Agent","volume":"62","author":"Zhang","year":"2019","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.jare.2021.02.006_b0130","doi-asserted-by":"crossref","DOI":"10.1016\/j.bcp.2020.113958","article-title":"DC591017, a phosphodiesterase-4 (PDE4) inhibitor with robust anti-inflammation through regulating PKA-CREB signaling","volume":"177","author":"Li","year":"2020","journal-title":"Biochem. Pharmacol."},{"issue":"9","key":"10.1016\/j.jare.2021.02.006_b0135","doi-asserted-by":"crossref","first-page":"5836","DOI":"10.4049\/jimmunol.0802999","article-title":"Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23\/IL-17 axis","volume":"182","author":"van der Fits","year":"2009","journal-title":"J. Immunol."},{"issue":"7","key":"10.1016\/j.jare.2021.02.006_b0140","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1111\/exd.12448","article-title":"Skin-penetrating methotrexate alleviates imiquimod-induced psoriasiform dermatitis via decreasing IL-17-producing gamma delta T cells","volume":"23","author":"Byamba","year":"2014","journal-title":"Exp. Dermatol."},{"key":"10.1016\/j.jare.2021.02.006_b0145","doi-asserted-by":"crossref","first-page":"7687","DOI":"10.1038\/ncomms8687","article-title":"Adiponectin regulates psoriasiform skin inflammation by suppressing IL-17 production from gammadelta-T cells","volume":"6","author":"Shibata","year":"2015","journal-title":"Nat. Commun."},{"issue":"12","key":"10.1016\/j.jare.2021.02.006_b0150","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1111\/all.12763","article-title":"PDK1\/Akt\/PDE4D axis identified as a target for asthma remedy synergistic with beta2 AR agonists by a natural agent arctigenin","volume":"70","author":"Fang","year":"2015","journal-title":"Allergy"},{"issue":"3","key":"10.1016\/j.jare.2021.02.006_b0155","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.jep.2009.01.038","article-title":"In vitro anti-inflammatory effects of arctigenin, a lignan from Arctium lappa L., through inhibition on iNOS pathway","volume":"122","author":"Zhao","year":"2009","journal-title":"J. Ethnopharmacol."},{"issue":"4","key":"10.1016\/j.jare.2021.02.006_b0160","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1085\/jgp.200709881","article-title":"Roles of GRK and PDE4 activities in the regulation of beta2 adrenergic signaling","volume":"131","author":"Xin","year":"2008","journal-title":"J. Gen. Physiol."},{"issue":"4","key":"10.1016\/j.jare.2021.02.006_b0165","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1007\/s10753-015-0115-3","article-title":"Arctigenin Protects against Lipopolysaccharide-Induced Pulmonary Oxidative Stress and Inflammation in a Mouse Model via Suppression of MAPK, HO-1, and iNOS Signaling","volume":"38","author":"Zhang","year":"2015","journal-title":"Inflammation"},{"key":"10.1016\/j.jare.2021.02.006_b0170","doi-asserted-by":"crossref","first-page":"376","DOI":"10.3389\/fphar.2017.00376","article-title":"Elucidation of Arctigenin Pharmacokinetics and Tissue Distribution after Intravenous, Oral, Hypodermic and Sublingual Administration in Rats and Beagle Dogs: Integration of In Vitro and In Vivo Findings","volume":"8","author":"Li","year":"2017","journal-title":"Front. Pharmacol."},{"issue":"12","key":"10.1016\/j.jare.2021.02.006_b0175","doi-asserted-by":"crossref","first-page":"1818","DOI":"10.1111\/cas.13086","article-title":"Phase I trial of GBS-01 for advanced pancreatic cancer refractory to gemcitabine","volume":"107","author":"Ikeda","year":"2016","journal-title":"Cancer Sci."},{"issue":"9","key":"10.1016\/j.jare.2021.02.006_b0180","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1080\/14728222.2017.1370454","article-title":"Targeting methionine cycle as a potential therapeutic strategy for immune disorders","volume":"21","author":"Li","year":"2017","journal-title":"Expert Opin. Ther. Targets"},{"issue":"2","key":"10.1016\/j.jare.2021.02.006_b0185","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1159\/000495291","article-title":"Psoriasis: Keratinocytes or Immune Cells \u2013 Which Is the Trigger?","volume":"235","author":"Benhadou","year":"2019","journal-title":"Dermatology"},{"issue":"1","key":"10.1016\/j.jare.2021.02.006_b0190","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s40246-018-0158-2","article-title":"Mutational analysis of epidermal and hyperproliferative type I keratins in mild and moderate psoriasis vulgaris patients: a possible role in the pathogenesis of psoriasis along with disease severity","volume":"12","author":"Tamilselvi","year":"2018","journal-title":"Hum. Genomics"},{"key":"10.1016\/j.jare.2021.02.006_b0195","first-page":"E6162","article-title":"Keratinocytes contribute intrinsically to psoriasis upon loss of Tnip1 function","volume":"11341","author":"Ippagunta","year":"2016","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"10","key":"10.1016\/j.jare.2021.02.006_b0200","doi-asserted-by":"crossref","first-page":"2168","DOI":"10.1016\/j.jid.2017.05.015","article-title":"Nrf2 promotes keratinocyte proliferation in psoriasis through up-regulation of Keratin 6, Keratin 16 and Keratin 17","volume":"137","author":"Yang","year":"2017","journal-title":"J. Invest. Dermatol."}],"container-title":["Journal of Advanced Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2090123221000321?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2090123221000321?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T20:52:04Z","timestamp":1761857524000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2090123221000321"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11]]},"references-count":40,"alternative-id":["S2090123221000321"],"URL":"https:\/\/doi.org\/10.1016\/j.jare.2021.02.006","relation":{},"ISSN":["2090-1232"],"issn-type":[{"value":"2090-1232","type":"print"}],"subject":[],"published":{"date-parts":[[2021,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Identification of phosphodiesterase-4 as the therapeutic target of arctigenin in alleviating psoriatic skin inflammation","name":"articletitle","label":"Article Title"},{"value":"Journal of Advanced Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jare.2021.02.006","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 The Authors. Published by Elsevier B.V. on behalf of Cairo University. This is an open access article under the CC BY license (http:\/\/creativecommons.org\/licenses\/by\/4.0\/).","name":"copyright","label":"Copyright"}]}}