{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T03:36:34Z","timestamp":1789616194970,"version":"build-2803163510"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82071005"],"award-info":[{"award-number":["82071005"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Endocrinol Invest"],"DOI":"10.1007\/s40618-025-02746-7","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T06:23:08Z","timestamp":1762755788000},"page":"547-559","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Puerarin suppress adipogenesis and inflammation on orbital fibroblasts from patients with thyroid eye disease"],"prefix":"10.1007","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0788-2523","authenticated-orcid":false,"given":"Lan","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijia","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuihong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honglei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4226-662X","authenticated-orcid":false,"given":"Dongmei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,10]]},"reference":[{"key":"2746_CR1","doi-asserted-by":"publisher","first-page":"G43","DOI":"10.1530\/EJE-21-0479","volume":"185","author":"L Bartalena","year":"2021","unstructured":"Bartalena L, Kahaly GJ, Baldeschi L et al (2021) The 2021 European group on graves\u2019 orbitopathy (EUGOGO) clinical practice guidelines for the medical management of graves\u2019 orbitopathy. Eur J Endocrinol 185:G43\u2013G67. https:\/\/doi.org\/10.1530\/EJE-21-0479","journal-title":"Eur J Endocrinol"},{"key":"2746_CR2","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1007\/s40618-020-01361-y","volume":"44","author":"PJ Dolman","year":"2021","unstructured":"Dolman PJ (2021) Dysthyroid optic neuropathy: evaluation and management. J Endocrinol Invest 44:421\u2013429. https:\/\/doi.org\/10.1007\/s40618-020-01361-y","journal-title":"J Endocrinol Invest"},{"key":"2746_CR3","doi-asserted-by":"publisher","first-page":"6352","DOI":"10.1167\/iovs.15-16870","volume":"56","author":"CY Kim","year":"2015","unstructured":"Kim CY, Lee HJ, Chae MK et al (2015) Therapeutic effect of Resveratrol on oxidative stress in graves\u2019 orbitopathy orbital fibroblasts. Investig Ophthalmol Vis Sci 56:6352\u20136361. https:\/\/doi.org\/10.1167\/iovs.15-16870","journal-title":"Investig Ophthalmol Vis Sci"},{"key":"2746_CR4","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1007\/s10792-025-03564-9","volume":"45","author":"J Dwivedi","year":"2025","unstructured":"Dwivedi J, Kaushal S, Arora P et al (2025) Molecular pathway and mechanism responsible for the progress of thyroid-associated orbitopathy. Int Ophthalmol 45:197. https:\/\/doi.org\/10.1007\/s10792-025-03564-9","journal-title":"Int Ophthalmol"},{"key":"2746_CR5","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1167\/iovs.66.9.68","volume":"66","author":"R Liu","year":"2025","unstructured":"Liu R, Xin X, Ma S et al (2025) Epac1 inhibits orbital fibroblast activation to ameliorate Thyroid-Associated Orbitopathy-Like features through the JAK\/STAT signaling pathway. Invest Ophthalmol Vis Sci 66:68. https:\/\/doi.org\/10.1167\/iovs.66.9.68","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2746_CR6","doi-asserted-by":"publisher","unstructured":"Aj RVDC C et al (2022) Enrichment of IGF-1R and PPAR\u03b3 signalling pathways in orbital inflammatory diseases: steps toward Understanding pathogenesis. Br J Ophthalmol 106. https:\/\/doi.org\/10.1136\/bjophthalmol-2020-318330","DOI":"10.1136\/bjophthalmol-2020-318330"},{"key":"2746_CR7","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1136\/bjophthalmol-2015-307399","volume":"100","author":"JJ Khong","year":"2016","unstructured":"Khong JJ, McNab AA, Ebeling PR et al (2016) Pathogenesis of thyroid eye disease: review and update on molecular mechanisms. Br J Ophthalmol 100:142\u2013150. https:\/\/doi.org\/10.1136\/bjophthalmol-2015-307399","journal-title":"Br J Ophthalmol"},{"key":"2746_CR8","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/j.ecl.2021.12.004","volume":"51","author":"TD Hoang","year":"2022","unstructured":"Hoang TD, Stocker DJ, Chou EL, Burch HB (2022) 2022 update on clinical management of graves\u2019 disease and thyroid eye disease. Endocrinol Metab Clin North Am 51:287\u2013304. https:\/\/doi.org\/10.1016\/j.ecl.2021.12.004","journal-title":"Endocrinol Metab Clin North Am"},{"key":"2746_CR9","doi-asserted-by":"publisher","first-page":"2347","DOI":"10.1002\/ptr.6417","volume":"33","author":"S Wang","year":"2019","unstructured":"Wang S, Yang F-J, Shang L-C et al (2019) Puerarin protects against high-fat high-sucrose diet-induced non-alcoholic fatty liver disease by modulating PARP-1\/PI3K\/AKT signaling pathway and facilitating mitochondrial homeostasis. Phytother Res 33:2347\u20132359. https:\/\/doi.org\/10.1002\/ptr.6417","journal-title":"Phytother Res"},{"key":"2746_CR10","doi-asserted-by":"publisher","first-page":"111325","DOI":"10.1016\/j.biopha.2021.111325","volume":"137","author":"Y Liu","year":"2021","unstructured":"Liu Y, Qiu Y, Chen Q et al (2021) Puerarin suppresses the hepatic gluconeogenesis via activation of PI3K\/Akt signaling pathway in diabetic rats and HepG2 cells. Biomed Pharmacother 137:111325. https:\/\/doi.org\/10.1016\/j.biopha.2021.111325","journal-title":"Biomed Pharmacother"},{"key":"2746_CR11","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1186\/s12944-023-01969-y","volume":"22","author":"M Yang","year":"2023","unstructured":"Yang M, Xia L, Song J et al (2023) Puerarin ameliorates metabolic dysfunction-associated fatty liver disease by inhibiting ferroptosis and inflammation. Lipids Health Dis 22:202. https:\/\/doi.org\/10.1186\/s12944-023-01969-y","journal-title":"Lipids Health Dis"},{"key":"2746_CR12","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1016\/j.freeradbiomed.2024.12.005","volume":"227","author":"S Jiang","year":"2025","unstructured":"Jiang S, Qiu S, Mu Y et al (2025) Puerarin reduces susceptibility to ventricular arrhythmias and inhibits ferroptosis via Sirt1\/Nrf2 signaling in high-fat-diet rats. Free Radic Biol Med 227:472\u2013484. https:\/\/doi.org\/10.1016\/j.freeradbiomed.2024.12.005","journal-title":"Free Radic Biol Med"},{"key":"2746_CR13","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1007\/s00210-023-02653-9","volume":"397","author":"W Deng","year":"2024","unstructured":"Deng W, Zhang W, He Q (2024) Study on the mechanism of puerarin against osteoarthritis from ferroptosis based on network Pharmacology and bioinformatics. Naunyn Schmiedebergs Arch Pharmacol 397:959\u2013968. https:\/\/doi.org\/10.1007\/s00210-023-02653-9","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"key":"2746_CR14","doi-asserted-by":"publisher","first-page":"156048","DOI":"10.1016\/j.phymed.2024.156048","volume":"135","author":"Q Tao","year":"2024","unstructured":"Tao Q, Liang Q, Fu Y et al (2024) Puerarin ameliorates colitis by direct suppression of macrophage M1 polarization in DSS mice. Phytomedicine 135:156048. https:\/\/doi.org\/10.1016\/j.phymed.2024.156048","journal-title":"Phytomedicine"},{"key":"2746_CR15","doi-asserted-by":"publisher","first-page":"155813","DOI":"10.1016\/j.phymed.2024.155813","volume":"132","author":"Z Hu","year":"2024","unstructured":"Hu Z, Chen D, Yan P et al (2024) Puerarin suppresses macrophage M1 polarization to alleviate renal inflammatory injury through antagonizing TLR4\/MyD88-mediated NF-\u03baB p65 and JNK\/FoxO1 activation. Phytomedicine 132:155813. https:\/\/doi.org\/10.1016\/j.phymed.2024.155813","journal-title":"Phytomedicine"},{"key":"2746_CR16","doi-asserted-by":"publisher","first-page":"109436","DOI":"10.1016\/j.exer.2023.109436","volume":"230","author":"F Shen","year":"2023","unstructured":"Shen F, Liu J, Fang L et al (2023) Development and application of animal models to study thyroid-associated ophthalmopathy. Exp Eye Res 230:109436. https:\/\/doi.org\/10.1016\/j.exer.2023.109436","journal-title":"Exp Eye Res"},{"key":"2746_CR17","doi-asserted-by":"publisher","first-page":"12200","DOI":"10.3390\/ijms222212200","volume":"22","author":"O Habanjar","year":"2021","unstructured":"Habanjar O, Diab-Assaf M, Caldefie-Chezet F, Delort L (2021) 3D cell culture systems: tumor Application, Advantages, and disadvantages. Int J Mol Sci 22:12200. https:\/\/doi.org\/10.3390\/ijms222212200","journal-title":"Int J Mol Sci"},{"key":"2746_CR18","doi-asserted-by":"publisher","first-page":"W357","DOI":"10.1093\/nar\/gkz382","volume":"47","author":"A Daina","year":"2019","unstructured":"Daina A, Michielin O, Zoete V (2019) SwissTargetPrediction: updated data and new features for efficient prediction of protein targets of small molecules. Nucleic Acids Res 47:W357\u2013W364. https:\/\/doi.org\/10.1093\/nar\/gkz382","journal-title":"Nucleic Acids Res"},{"key":"2746_CR19","doi-asserted-by":"publisher","first-page":"W32","DOI":"10.1093\/nar\/gku293","volume":"42","author":"D Gfeller","year":"2014","unstructured":"Gfeller D, Grosdidier A, Wirth M et al (2014) SwissTargetPrediction: a web server for target prediction of bioactive small molecules. Nucleic Acids Res 42:W32\u201338. https:\/\/doi.org\/10.1093\/nar\/gku293","journal-title":"Nucleic Acids Res"},{"key":"2746_CR20","doi-asserted-by":"publisher","first-page":"D609","DOI":"10.1093\/nar\/gkae1010","volume":"53","author":"The UniProt Consortium","year":"2025","unstructured":"The UniProt Consortium (2025) UniProt: the universal protein knowledgebase in 2025. Nucleic Acids Res 53:D609\u2013D617. https:\/\/doi.org\/10.1093\/nar\/gkae1010","journal-title":"Nucleic Acids Res"},{"key":"2746_CR21","doi-asserted-by":"publisher","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","volume":"51","author":"D Szklarczyk","year":"2023","unstructured":"Szklarczyk D, Kirsch R, Koutrouli M et al (2023) The STRING database in 2023: protein-protein association networks and functional enrichment analyses for any sequenced genome of interest. Nucleic Acids Res 51:D638\u2013D646. https:\/\/doi.org\/10.1093\/nar\/gkac1000","journal-title":"Nucleic Acids Res"},{"key":"2746_CR22","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1101\/gr.1239303","volume":"13","author":"P Shannon","year":"2003","unstructured":"Shannon P, Markiel A, Ozier O et al (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13:2498\u20132504. https:\/\/doi.org\/10.1101\/gr.1239303","journal-title":"Genome Res"},{"key":"2746_CR23","doi-asserted-by":"publisher","first-page":"W216","DOI":"10.1093\/nar\/gkac194","volume":"50","author":"BT Sherman","year":"2022","unstructured":"Sherman BT, Hao M, Qiu J et al (2022) DAVID: a web server for functional enrichment analysis and functional annotation of gene lists (2021 update). Nucleic Acids Res 50:W216\u2013W221. https:\/\/doi.org\/10.1093\/nar\/gkac194","journal-title":"Nucleic Acids Res"},{"key":"2746_CR24","doi-asserted-by":"publisher","first-page":"W159","DOI":"10.1093\/nar\/gkac394","volume":"50","author":"Y Liu","year":"2022","unstructured":"Liu Y, Yang X, Gan J et al (2022) CB-Dock2: improved protein\u2013ligand blind Docking by integrating cavity detection, Docking and homologous template fitting. Nucleic Acids Res 50:W159\u2013W164. https:\/\/doi.org\/10.1093\/nar\/gkac394","journal-title":"Nucleic Acids Res"},{"key":"2746_CR25","doi-asserted-by":"publisher","first-page":"177732","DOI":"10.1016\/j.ejphar.2025.177732","volume":"1000","author":"S Wang","year":"2025","unstructured":"Wang S, Liu Y, Cui M et al (2025) Cinnamaldehyde enhances the intervention effect of puerarin on stroke from the perspectives of pharmacokinetics and pharmacodynamics. Eur J Pharmacol 1000:177732. https:\/\/doi.org\/10.1016\/j.ejphar.2025.177732","journal-title":"Eur J Pharmacol"},{"key":"2746_CR26","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1167\/tvst.12.6.12","volume":"12","author":"W Wang","year":"2023","unstructured":"Wang W, Zhang J-W, Qin Y-J et al (2023) Establishment and comparison of two different animal models of graves\u2019 orbitopathy. Transl Vis Sci Technol 12:12. https:\/\/doi.org\/10.1167\/tvst.12.6.12","journal-title":"Transl Vis Sci Technol"},{"key":"2746_CR27","doi-asserted-by":"publisher","first-page":"4966","DOI":"10.4049\/jimmunol.162.8.4966","volume":"162","author":"MC Many","year":"1999","unstructured":"Many MC, Costagliola S, Detrait M et al (1999) Development of an animal model of autoimmune thyroid eye disease. J Immunol 162:4966\u20134974","journal-title":"J Immunol"},{"key":"2746_CR28","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1007\/s10456-011-9227-z","volume":"14","author":"SR Pickens","year":"2011","unstructured":"Pickens SR, Chamberlain ND, Volin MV et al (2011) Anti-CXCL5 therapy ameliorates IL-17-induced arthritis by decreasing joint vascularization. Angiogenesis 14:443\u2013455. https:\/\/doi.org\/10.1007\/s10456-011-9227-z","journal-title":"Angiogenesis"},{"key":"2746_CR29","doi-asserted-by":"publisher","first-page":"CD001989","DOI":"10.1002\/14651858.CD001989.pub3","volume":"1","author":"JC Lin","year":"2023","unstructured":"Lin JC, Song S, Ng SM et al (2023) Interventions for acute non-arteritic central retinal artery occlusion. Cochrane Database Syst Rev 1:CD001989. https:\/\/doi.org\/10.1002\/14651858.CD001989.pub3","journal-title":"Cochrane Database Syst Rev"},{"key":"2746_CR30","doi-asserted-by":"publisher","first-page":"11636","DOI":"10.1080\/21655979.2022.2070586","volume":"13","author":"H Tang","year":"2022","unstructured":"Tang H, Kong L, Yang Y et al (2022) Puerarin suppresses hypoxia-induced vascular endothelial growth factor upregulation in human retinal pigmented epithelial cells by blocking JAK2\/STAT3 pathway. Bioengineered 13:11636\u201311645. https:\/\/doi.org\/10.1080\/21655979.2022.2070586","journal-title":"Bioengineered"},{"key":"2746_CR31","doi-asserted-by":"publisher","first-page":"114524","DOI":"10.1016\/j.ejpb.2024.114524","volume":"204","author":"Y Long","year":"2024","unstructured":"Long Y, Hu J, Liu Y et al (2024) Development of puerarin-loaded poly(lactic acid) microspheres for sustained ocular delivery: in vitro\/vivo evaluation. Eur J Pharm Biopharm 204:114524. https:\/\/doi.org\/10.1016\/j.ejpb.2024.114524","journal-title":"Eur J Pharm Biopharm"}],"container-title":["Journal of Endocrinological Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40618-025-02746-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40618-025-02746-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40618-025-02746-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T05:17:53Z","timestamp":1774415873000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40618-025-02746-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,10]]},"references-count":31,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["2746"],"URL":"https:\/\/doi.org\/10.1007\/s40618-025-02746-7","relation":{},"ISSN":["1720-8386"],"issn-type":[{"value":"1720-8386","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,10]]},"assertion":[{"value":"8 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 November 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The datasets generated during and\/or analysed during the current study are available from the corresponding author on reasonable request.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data availablity"}},{"value":"Written informed consent was obtained from all the patients. This study was approved by the Ethics Committee of Beijing Tongren Hospital (NO.TRECKY2018-056-GZ(2022)-07).","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent and ethics approval"}}]}}