{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T10:56:56Z","timestamp":1774004216026,"version":"3.50.1"},"reference-count":35,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT, South Korea","doi-asserted-by":"publisher","award":["RS-2025-16068439"],"award-info":[{"award-number":["RS-2025-16068439"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004085","name":"Ministry of Education, Science and Technology","doi-asserted-by":"publisher","award":["2021R1I1A2055834"],"award-info":[{"award-number":["2021R1I1A2055834"]}],"id":[{"id":"10.13039\/501100004085","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2023A1515012483"],"award-info":[{"award-number":["2023A1515012483"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002462","name":"Chungnam National University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002462","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2018R1D1A1B07050779"],"award-info":[{"award-number":["2018R1D1A1B07050779"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["iScience"],"published-print":{"date-parts":[[2026,1]]},"DOI":"10.1016\/j.isci.2025.114292","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T16:45:22Z","timestamp":1764607522000},"page":"114292","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["GSK3\u03b2\/HIF-1\u03b1 signaling-dependent anti-parasite effect of Cynanchi atrati Radix"],"prefix":"10.1016","volume":"29","author":[{"given":"Fei-Fei","family":"Gao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guan-Hao","family":"Hong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin-Cheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia-hui","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Sun","family":"Yun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"In-Wook","family":"Choi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae-Min","family":"Yuk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin-tian","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gang Min","family":"Hur","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2639-1727","authenticated-orcid":false,"given":"Guang-Ho","family":"Cha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.isci.2025.114292_bib1","doi-asserted-by":"crossref","first-page":"R770","DOI":"10.1016\/j.cub.2018.05.035","article-title":"Toxoplasma gondii","volume":"28","author":"Kochanowsky","year":"2018","journal-title":"Curr. Biol."},{"key":"10.1016\/j.isci.2025.114292_bib2","doi-asserted-by":"crossref","first-page":"103","DOI":"10.3389\/fcimb.2019.00103","article-title":"Mechanisms of Human Innate Immune Evasion by Toxoplasma gondii","volume":"9","author":"Lima","year":"2019","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"10.1016\/j.isci.2025.114292_bib3","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.ijpara.2008.08.002","article-title":"The immunobiology of the innate response to Toxoplasma gondii","volume":"39","author":"Miller","year":"2009","journal-title":"Int. J. Parasitol."},{"key":"10.1016\/j.isci.2025.114292_bib4","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2021.114748","article-title":"A review of the ethnopharmacology, phytochemistry and pharmacology of Cynanchumatratum","volume":"284","author":"Zhang","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.isci.2025.114292_bib5","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/j.phymed.2016.02.017","article-title":"In vitro activity of (-)-deoxypergularinine, on its own and in combination with anti-tubercular drugs, against resistant strains of Mycobacterium tuberculosis","volume":"23","author":"Nam","year":"2016","journal-title":"Phytomedicine"},{"key":"10.1016\/j.isci.2025.114292_bib6","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.fitote.2014.03.027","article-title":"Seco-pregnane steroidal glycosides from the roots of Cynanchum atratum and their anti-TMV activity","volume":"97","author":"Yan","year":"2014","journal-title":"Fitoterapia"},{"key":"10.1016\/j.isci.2025.114292_bib7","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1094\/PDIS-05-22-1261-PDN","article-title":"First Report of Alternaria alternata Causing Leaf Spot of Cynanchum atratum in China","volume":"107","author":"Sun","year":"2023","journal-title":"Plant Dis."},{"key":"10.1016\/j.isci.2025.114292_bib8","first-page":"751-2","article-title":"[Antifebrile and anti-inflammatory effects of radix Cynanchi atrati]","volume":"20","author":"Xue","year":"1995","journal-title":"Zhongguo Zhongyao Zazhi"},{"key":"10.1016\/j.isci.2025.114292_bib9","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1021\/np000428b","article-title":"Bioactive constituents of the roots of Cynanchum atratum","volume":"64","author":"Day","year":"2001","journal-title":"J. Nat. Prod."},{"key":"10.1016\/j.isci.2025.114292_bib10","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1016\/j.jep.2011.06.022","article-title":"Water extract of Cynanchi atrati Radix regulates inflammation and apoptotic cell death through suppression of IKK-mediated NF-\u03baB signaling","volume":"137","author":"Jeon","year":"2011","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.isci.2025.114292_bib11","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1002\/pca.998","article-title":"Identification and quantification of C21 steroidal saponins from Radix Cynanchi Atrati by high-performance liquid chromatography with evaporative light scattering detection and electrospray mass spectrometric detection","volume":"18","author":"Liang","year":"2007","journal-title":"Phytochem. Anal."},{"key":"10.1016\/j.isci.2025.114292_bib12","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.steroids.2008.10.007","article-title":"Twelve pregnane glycosides from Cynanchum atratum","volume":"74","author":"Bai","year":"2009","journal-title":"Steroids"},{"key":"10.1016\/j.isci.2025.114292_bib13","first-page":"1895","article-title":"[Studies on chemical constituents from root of Cynanchum atratum]","volume":"32","author":"Yuan","year":"2007","journal-title":"Zhongguo Zhongyao Zazhi"},{"key":"10.1016\/j.isci.2025.114292_bib14","doi-asserted-by":"crossref","first-page":"184","DOI":"10.3389\/fcimb.2020.00184","article-title":"VEGF Production Is Regulated by the AKT\/ERK1\/2 Signaling Pathway and Controls the Proliferation of Toxoplasma gondii in ARPE-19 Cells","volume":"10","author":"Quan","year":"2020","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"10.1016\/j.isci.2025.114292_bib15","doi-asserted-by":"crossref","first-page":"461","DOI":"10.3347\/kjp.2020.58.4.461","article-title":"Neuroprotective Effect of Chronic Intracranial Toxoplasma gondii Infection in a Mouse Cerebral Ischemia Model","volume":"58","author":"Lee","year":"2020","journal-title":"Korean J. Parasitol."},{"key":"10.1016\/j.isci.2025.114292_bib16","doi-asserted-by":"crossref","first-page":"26852","DOI":"10.1074\/jbc.M110.147041","article-title":"Toxoplasma gondii activates hypoxia-inducible factor (HIF) by stabilizing the HIF-1alpha subunit via type I activin-like receptor kinase receptor signaling","volume":"285","author":"Wiley","year":"2010","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.isci.2025.114292_bib17","doi-asserted-by":"crossref","first-page":"8635","DOI":"10.1158\/0008-5472.CAN-08-0917","article-title":"Sphingosine kinase 1: a new modulator of hypoxia inducible factor 1alpha during hypoxia in human cancer cells","volume":"68","author":"Ader","year":"2008","journal-title":"Cancer Res."},{"key":"10.1016\/j.isci.2025.114292_bib18","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1182\/blood-2011-08-375014","article-title":"GSK-3\u03b2 regulates cell growth, migration, and angiogenesis via Fbw7 and USP28-dependent degradation of HIF-1\u03b1","volume":"119","author":"Fl\u00fcgel","year":"2012","journal-title":"Blood"},{"key":"10.1016\/j.isci.2025.114292_bib19","doi-asserted-by":"crossref","first-page":"11","DOI":"10.3389\/fcell.2016.00011","article-title":"Hypoxia-Inducible Factors (HIFs) and Phosphorylation: Impact on Stability, Localization, and Transactivity","volume":"4","author":"Kietzmann","year":"2016","journal-title":"Front. Cell Dev. Biol."},{"key":"10.1016\/j.isci.2025.114292_bib20","doi-asserted-by":"crossref","DOI":"10.1016\/j.actatropica.2020.105560","article-title":"Toxoplasma gondii Chinese I genotype Wh6 strain infection induces tau phosphorylation via activating GSK3\u03b2 and causes hippocampal neuron apoptosis","volume":"210","author":"Tao","year":"2020","journal-title":"Acta Trop."},{"key":"10.1016\/j.isci.2025.114292_bib21","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.39887","article-title":"Characterization of a Toxoplasma effector uncovers an alternative GSK3\/\u03b2-catenin-regulatory pathway of inflammation","volume":"7","author":"He","year":"2018","journal-title":"eLife"},{"key":"10.1016\/j.isci.2025.114292_bib22","article-title":"The essential kinase TgGSK regulates centrosome division and endodyogeny in Toxoplasma gondii","author":"Krueger","year":"2024","journal-title":"bioRxiv"},{"key":"10.1016\/j.isci.2025.114292_bib23","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1038\/cdd.2016.101","article-title":"Leishmania donovani inhibits macrophage apoptosis and pro-inflammatory response through AKT-mediated regulation of \u03b2-catenin and FOXO-1","volume":"23","author":"Gupta","year":"2016","journal-title":"Cell Death Differ."},{"key":"10.1016\/j.isci.2025.114292_bib24","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.00462-15","article-title":"siRNA Screening Identifies the Host Hexokinase 2 (HK2) Gene as an Important Hypoxia-Inducible Transcription Factor 1 (HIF-1) Target Gene in Toxoplasma gondii-Infected Cells","volume":"6","author":"Menendez","year":"2015","journal-title":"mBio"},{"key":"10.1016\/j.isci.2025.114292_bib25","doi-asserted-by":"crossref","first-page":"31277","DOI":"10.1074\/jbc.M300763200","article-title":"Regulation of hypoxia-inducible factor-1alpha protein level during hypoxic conditions by the phosphatidylinositol 3-kinase\/Akt\/glycogen synthase kinase 3beta pathway in HepG2 cells","volume":"278","author":"Mottet","year":"2003","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.isci.2025.114292_bib26","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1007\/s40268-017-0206-8","article-title":"Adverse Event Profile of Pyrimethamine-Based Therapy in Toxoplasmosis: A Systematic Review","volume":"17","author":"Ben-Harari","year":"2017","journal-title":"Drugs R&D"},{"key":"10.1016\/j.isci.2025.114292_bib27","doi-asserted-by":"crossref","DOI":"10.1128\/CMR.00057-17","article-title":"Treatment of Toxoplasmosis: Historical Perspective, Animal Models, and Current Clinical Practice","volume":"31","author":"Dunay","year":"2018","journal-title":"Clin. Microbiol. Rev."},{"key":"10.1016\/j.isci.2025.114292_bib28","doi-asserted-by":"crossref","DOI":"10.1016\/j.phytochem.2025.114442","article-title":"Anti-Toxoplasma gondii screening of eight species used in Cote d'Ivoire, and bio-guided isolation of three previously undescribed nor-sesquiterpenoids and one benzyl glycoside from Elaeis guineensis leaves","volume":"234","author":"Ouattara","year":"2025","journal-title":"Phytochemistry"},{"key":"10.1016\/j.isci.2025.114292_bib29","doi-asserted-by":"crossref","first-page":"36","DOI":"10.3389\/fcimb.2019.00036","article-title":"The Activin Receptor, Activin-Like Kinase 4, Mediates Toxoplasma Gondii Activation of Hypoxia Inducible Factor-1","volume":"9","author":"Lis","year":"2019","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"10.1016\/j.isci.2025.114292_bib30","first-page":"5731","article-title":"HIF-1alpha-mediated up-regulation of vascular endothelial growth factor, independent of basic fibroblast growth factor, is important in the switch to the angiogenic phenotype during early tumorigenesis","volume":"61","author":"Fang","year":"2001","journal-title":"Cancer Res."},{"key":"10.1016\/j.isci.2025.114292_bib31","doi-asserted-by":"crossref","first-page":"22423","DOI":"10.1073\/pnas.2014639117","article-title":"4-Hydroxyacetophenone modulates the actomyosin cytoskeleton to reduce metastasis","volume":"117","author":"Bryan","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.isci.2025.114292_bib32","doi-asserted-by":"crossref","first-page":"542","DOI":"10.20546\/ijcmas.2019.812.072","article-title":"An experimental study on the effect of pyrimethamine-loaded niosomes in the treatment of acute toxoplasmosis","volume":"8","author":"El Mansory","year":"2019","journal-title":"Int. J. Curr. Microbiol. Appl. Sci."},{"key":"10.1016\/j.isci.2025.114292_bib33","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.jep.2014.02.037","article-title":"Anti-melanoma activity of Cynanchi atrati Radix is mediated by regulation of NF-kappa B activity and pro-apoptotic proteins","volume":"153","author":"Son","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.isci.2025.114292_bib34","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1128\/EC.3.4.992-1003.2004","article-title":"Dynamics of Toxoplasma gondii differentiation","volume":"3","author":"Dzierszinski","year":"2004","journal-title":"Eukaryot. Cell"},{"key":"10.1016\/j.isci.2025.114292_bib35","doi-asserted-by":"crossref","first-page":"6437","DOI":"10.1073\/pnas.1316841111","article-title":"Avirulent strains of Toxoplasma gondii infect macrophages by active invasion from the phagosome","volume":"111","author":"Zhao","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["iScience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589004225025532?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589004225025532?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T08:41:31Z","timestamp":1773996091000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2589004225025532"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":35,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["S2589004225025532"],"URL":"https:\/\/doi.org\/10.1016\/j.isci.2025.114292","relation":{},"ISSN":["2589-0042"],"issn-type":[{"value":"2589-0042","type":"print"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"GSK3\u03b2\/HIF-1\u03b1 signaling-dependent anti-parasite effect of Cynanchi atrati Radix","name":"articletitle","label":"Article Title"},{"value":"iScience","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.isci.2025.114292","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"114292"}}