{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T23:32:51Z","timestamp":1790983971702,"version":"4.1.0"},"reference-count":39,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82201808"],"award-info":[{"award-number":["82201808"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Phytomedicine"],"published-print":{"date-parts":[[2024,2]]},"DOI":"10.1016\/j.phymed.2023.155280","type":"journal-article","created":{"date-parts":[[2023,12,17]],"date-time":"2023-12-17T10:08:22Z","timestamp":1702807702000},"page":"155280","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":13,"special_numbering":"C","title":["Troxerutin dampened hypothalamic neuroinflammation via microglial IL-22\/IL-22R1\/IRF3 activation in dihydrotestosterone-induced polycystic ovary syndrome rats"],"prefix":"10.1016","volume":"124","author":[{"given":"Zixuan","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huihui","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueli","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Zhuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renyu","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuying","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaonan","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7617-5438","authenticated-orcid":false,"given":"Ruiqin","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.phymed.2023.155280_bib0001","doi-asserted-by":"crossref","DOI":"10.1016\/j.bcp.2022.115026","article-title":"Regulation of IRF3 activation in human antiviral signaling pathways","volume":"200","author":"Al Hamrashdi","year":"2022","journal-title":"Biochem. Pharmacol."},{"issue":"2","key":"10.1016\/j.phymed.2023.155280_bib0002","doi-asserted-by":"crossref","DOI":"10.3390\/nu13020520","article-title":"Hypothalamic inflammation as a potential pathophysiologic basis for the heterogeneity of clinical, hormonal, and metabolic presentation in PCOS","volume":"13","author":"Barlampa","year":"2021","journal-title":"Nutrients"},{"issue":"8","key":"10.1016\/j.phymed.2023.155280_bib0003","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1002\/glia.23846","article-title":"Regulatory function of microRNAs in microglia","volume":"68","author":"Brites","year":"2020","journal-title":"Glia"},{"key":"10.1016\/j.phymed.2023.155280_bib0004","doi-asserted-by":"crossref","first-page":"458","DOI":"10.3389\/fncel.2018.00458","article-title":"The interleukin-10 family of cytokines and their role in the CNS","volume":"12","author":"Burmeister","year":"2018","journal-title":"Front. Cell Neurosci."},{"issue":"10","key":"10.1016\/j.phymed.2023.155280_bib0006","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1038\/ncpendmet0637","article-title":"The reproductive phenotype in polycystic ovary syndrome","volume":"3","author":"Chang","year":"2007","journal-title":"Nat. Clin. Pract. Endocrinol. Metab."},{"issue":"6","key":"10.1016\/j.phymed.2023.155280_bib0007","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1038\/s41593-018-0145-x","article-title":"Microglial immune checkpoint mechanisms","volume":"21","author":"Deczkowska","year":"2018","journal-title":"Nat. Neurosci."},{"issue":"6","key":"10.1016\/j.phymed.2023.155280_bib0008","doi-asserted-by":"crossref","first-page":"e13136","DOI":"10.1111\/jne.13136","article-title":"Unusual suspects: glial cells in fertility regulation and their suspected role in polycystic ovary syndrome","volume":"34","author":"Desroziers","year":"2022","journal-title":"J. Neuroendocrinol."},{"issue":"5","key":"10.1016\/j.phymed.2023.155280_bib0009","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1210\/er.2015-1018","article-title":"Scientific statement on the diagnostic criteria, epidemiology, pathophysiology, and molecular genetics of polycystic ovary syndrome","volume":"36","author":"Dumesic","year":"2015","journal-title":"Endocr. Rev."},{"issue":"5","key":"10.1016\/j.phymed.2023.155280_bib0010","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/nrendo.2018.24","article-title":"Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment","volume":"14","author":"Escobar-Morreale","year":"2018","journal-title":"Nat. Rev. Endocrinol."},{"issue":"1","key":"10.1016\/j.phymed.2023.155280_bib0011","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1186\/s13048-020-00701-z","article-title":"Troxerutin protects against DHT-induced polycystic ovary syndrome in rats","volume":"13","author":"Gao","year":"2020","journal-title":"J. Ovarian Res."},{"issue":"5","key":"10.1016\/j.phymed.2023.155280_bib0012","doi-asserted-by":"crossref","first-page":"E405","DOI":"10.1152\/ajpendo.00150.2022","article-title":"Troxerutin attenuates insulin resistance via pancreatic IL-22\/JAK1\/STAT3 signaling activation in dihydrotestosterone-induced polycystic ovary syndrome rats","volume":"323","author":"Gao","year":"2022","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"10.1016\/j.phymed.2023.155280_bib0013","doi-asserted-by":"crossref","DOI":"10.1016\/j.expneurol.2021.113947","article-title":"C1q inhibits differentiation of oligodendrocyte progenitor cells via Wnt\/\u03b2-catenin signaling activation in a cuprizone-induced mouse model of multiple sclerosis","volume":"348","author":"Gao","year":"2022","journal-title":"Exp. Neurol."},{"issue":"4","key":"10.1016\/j.phymed.2023.155280_bib0014","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/nrendo.2010.217","article-title":"Polycystic ovary syndrome: etiology, pathogenesis and diagnosis","volume":"7","author":"Goodarzi","year":"2011","journal-title":"Nat. Rev. Endocrinol."},{"issue":"5","key":"10.1016\/j.phymed.2023.155280_bib0015","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1007\/s11011-019-00454-9","article-title":"Troxerutin exerts neuroprotection against lipopolysaccharide (LPS) induced oxidative stress and neuroinflammation through targeting SIRT1\/SIRT3 signaling pathway","volume":"34","author":"Jamali-Raeufy","year":"2019","journal-title":"Metab. Brain Dis."},{"issue":"2","key":"10.1016\/j.phymed.2023.155280_bib0016","doi-asserted-by":"crossref","DOI":"10.3390\/ijms23020757","article-title":"The roles of IL-22 and its receptor in the regulation of inflammatory responses in the brain","volume":"23","author":"Lee","year":"2022","journal-title":"Int. J. Mol. Sci."},{"issue":"3","key":"10.1016\/j.phymed.2023.155280_bib0017","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/s41582-020-00435-y","article-title":"Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here?","volume":"17","author":"Leng","year":"2021","journal-title":"Nat. Rev. Neurol."},{"issue":"2","key":"10.1016\/j.phymed.2023.155280_bib0018","doi-asserted-by":"crossref","DOI":"10.3390\/nu14020279","article-title":"Yogurt enriched with inulin ameliorated reproductive functions and regulated gut microbiota in dehydroepiandrosterone-induced polycystic ovary syndrome mice","volume":"14","author":"Li","year":"2022","journal-title":"Nutrients"},{"issue":"10","key":"10.1016\/j.phymed.2023.155280_bib0019","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1084\/jem.20061308","article-title":"Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides","volume":"203","author":"Liang","year":"2006","journal-title":"J. Exp. Med."},{"issue":"3","key":"10.1016\/j.phymed.2023.155280_bib0020","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.physbeh.2009.05.020","article-title":"Hyperandrogenemia, psychological distress, and food cravings in young women","volume":"98","author":"Lim","year":"2009","journal-title":"Physiol. Behav."},{"key":"10.1016\/j.phymed.2023.155280_bib0021","doi-asserted-by":"crossref","first-page":"215","DOI":"10.3389\/fncel.2018.00215","article-title":"Microglia responses to pro-inflammatory stimuli (LPS, IFN\u03b3+TNF\u03b1) and reprogramming by resolving cytokines (IL-4, IL-10)","volume":"12","author":"Lively","year":"2018","journal-title":"Front. Cell Neurosci."},{"issue":"4","key":"10.1016\/j.phymed.2023.155280_bib0022","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1111\/bph.13139","article-title":"Microglial M1\/M2 polarization and metabolic states","volume":"173","author":"Orihuela","year":"2016","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.phymed.2023.155280_bib0023","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1186\/s12974-015-0335-3","article-title":"Interleukin-22 is increased in multiple sclerosis patients and targets astrocytes","volume":"12","author":"Perriard","year":"2015","journal-title":"J. Neuroinflamm."},{"issue":"1","key":"10.1016\/j.phymed.2023.155280_bib0024","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1186\/s12974-017-1024-1","article-title":"Lysophosphatidic acid via LPA-receptor 5\/protein kinase D-dependent pathways induces a motile and pro-inflammatory microglial phenotype","volume":"14","author":"Plastira","year":"2017","journal-title":"J. Neuroinflamm."},{"issue":"2","key":"10.1016\/j.phymed.2023.155280_bib0025","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1530\/JOE-19-0589","article-title":"The therapeutic effect of interleukin-22 in high androgen-induced polycystic ovary syndrome","volume":"245","author":"Qi","year":"2020","journal-title":"J. Endocrinol."},{"issue":"8","key":"10.1016\/j.phymed.2023.155280_bib0026","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1038\/s41591-019-0509-0","article-title":"Gut microbiota-bile acid-interleukin-22 axis orchestrates polycystic ovary syndrome","volume":"25","author":"Qi","year":"2019","journal-title":"Nat. Med."},{"issue":"2","key":"10.1016\/j.phymed.2023.155280_bib0027","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1097\/MPA.0b013e3181594258","article-title":"Interleukin 22 receptor 1 expression in pancreas islets","volume":"36","author":"Shioya","year":"2008","journal-title":"Pancreas"},{"issue":"1","key":"10.1016\/j.phymed.2023.155280_bib0028","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1186\/s12974-019-1641-y","article-title":"DHEA attenuates microglial activation via induction of JMJD3 in experimental subarachnoid haemorrhage","volume":"16","author":"Tao","year":"2019","journal-title":"J. Neuroinflamm."},{"issue":"12","key":"10.1016\/j.phymed.2023.155280_bib0029","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1002\/glia.21233","article-title":"Interferon regulatory factor 3 inhibits astrocyte inflammatory gene expression through suppression of the proinflammatory miR-155 and miR-155*","volume":"59","author":"Tarassishin","year":"2011","journal-title":"Glia"},{"key":"10.1016\/j.phymed.2023.155280_bib0030","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1186\/1742-2094-8-187","article-title":"Interferon regulatory factor 3 plays an anti-inflammatory role in microglia by activating the PI3K\/Akt pathway","volume":"8","author":"Tarassishin","year":"2011","journal-title":"J. Neuroinflamm."},{"issue":"8","key":"10.1016\/j.phymed.2023.155280_bib0031","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1038\/ni.1770","article-title":"Identification of a human helper T cell population that has abundant production of interleukin 22 and is distinct from T(H)-17, T(H)1 and T(H)2 cells","volume":"10","author":"Trifari","year":"2009","journal-title":"Nat. Immunol."},{"issue":"6","key":"10.1016\/j.phymed.2023.155280_bib0032","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1507\/endocrj.K09E-185","article-title":"GnRH pulsatility, the pituitary response and reproductive dysfunction","volume":"56","author":"Tsutsumi","year":"2009","journal-title":"Endocr. J."},{"issue":"12","key":"10.1016\/j.phymed.2023.155280_bib0033","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/j.tem.2018.08.005","article-title":"New perspectives on the pathogenesis of PCOS: neuroendocrine origins","volume":"29","author":"Walters","year":"2018","journal-title":"Trends Endocrinol. Metab."},{"issue":"7521","key":"10.1016\/j.phymed.2023.155280_bib0034","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/nature13564","article-title":"Interleukin-22 alleviates metabolic disorders and restores mucosal immunity in diabetes","volume":"514","author":"Wang","year":"2014","journal-title":"Nature"},{"issue":"11","key":"10.1016\/j.phymed.2023.155280_bib0035","doi-asserted-by":"crossref","first-page":"5397","DOI":"10.4049\/jimmunol.168.11.5397","article-title":"Cutting edge: immune cells as sources and targets of the IL-10 family members?","volume":"168","author":"Wolk","year":"2002","journal-title":"J. Immunol."},{"issue":"1","key":"10.1016\/j.phymed.2023.155280_bib0036","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s00281-009-0188-x","article-title":"Biology of interleukin-22","volume":"32","author":"Wolk","year":"2010","journal-title":"Semin. Immunopathol."},{"issue":"1","key":"10.1016\/j.phymed.2023.155280_bib0037","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s12035-022-03074-0","article-title":"Protective role of acetate against depressive-like behaviour associated with letrozole-induced PCOS rat model: involvement of HDAC2 and DNA methylation","volume":"60","author":"Wolugbom","year":"2023","journal-title":"Mol. Neurobiol."},{"key":"10.1016\/j.phymed.2023.155280_bib0038","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.brainresbull.2018.09.014","article-title":"S100A8\/A9 induces microglia activation and promotes the apoptosis of oligodendrocyte precursor cells by activating the NF-\u03baB signaling pathway","volume":"143","author":"Wu","year":"2018","journal-title":"Brain Res. Bull."},{"key":"10.1016\/j.phymed.2023.155280_bib0039","article-title":"Troxerutin stimulates osteoblast differentiation of mesenchymal stem cell and facilitates bone fracture healing","volume":"12","author":"Yang","year":"2021","journal-title":"Front. Pharmacol."},{"issue":"4","key":"10.1016\/j.phymed.2023.155280_bib0040","doi-asserted-by":"crossref","first-page":"e13685","DOI":"10.1111\/aji.13685","article-title":"The T(H) 22-mediated IL-22 deficiency associated with premature ovarian insufficiency","volume":"89","author":"Zhang","year":"2023","journal-title":"Am. J. Reprod. Immunol."}],"container-title":["Phytomedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0944711323006384?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0944711323006384?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T23:45:13Z","timestamp":1777592713000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0944711323006384"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2]]},"references-count":39,"alternative-id":["S0944711323006384"],"URL":"https:\/\/doi.org\/10.1016\/j.phymed.2023.155280","relation":{},"ISSN":["0944-7113"],"issn-type":[{"value":"0944-7113","type":"print"}],"subject":[],"published":{"date-parts":[[2024,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Troxerutin dampened hypothalamic neuroinflammation via microglial IL-22\/IL-22R1\/IRF3 activation in dihydrotestosterone-induced polycystic ovary syndrome rats","name":"articletitle","label":"Article Title"},{"value":"Phytomedicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.phymed.2023.155280","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 Elsevier GmbH. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"155280"}}