{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T04:57:48Z","timestamp":1790485068940,"version":"4.1.0"},"reference-count":49,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"Korea government","doi-asserted-by":"publisher","award":["RS-2025-23323186"],"award-info":[{"award-number":["RS-2025-23323186"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"award":["RS-2025-23323186"],"award-info":[{"award-number":["RS-2025-23323186"]}],"id":[{"id":"https:\/\/ror.org\/01wpjm123","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Ministry of Education","award":["2026-ANCHOR-10-002"],"award-info":[{"award-number":["2026-ANCHOR-10-002"]}]},{"name":"Ministry of Education","award":["RS-2022-NF000886"],"award-info":[{"award-number":["RS-2022-NF000886"]}]},{"award":["2026-ANCHOR-10-002"],"award-info":[{"award-number":["2026-ANCHOR-10-002"]}],"id":[{"id":"https:\/\/ror.org\/01p262204","id-type":"ROR","asserted-by":"publisher"}]},{"award":["RS-2022-NF000886"],"award-info":[{"award-number":["RS-2022-NF000886"]}],"id":[{"id":"https:\/\/ror.org\/01p262204","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Epilepsy is a chronic neurological disorder in which current antiseizure medications are limited by incomplete seizure control and variable therapeutic responses, highlighting the need to identify new bioactive candidates. Passiflora incarnata (P. incarnata) has demonstrated neuropharmacological and anticonvulsant properties. However, the individual phytochemicals and molecular mechanisms underlying these effects remain incompletely characterized. In this study, we integrated network pharmacology with cellular validation to identify epilepsy-relevant phytochemicals of P. incarnata and evaluate their neuroprotective effects. Eleven phytochemicals underwent target prediction and were compared with epilepsy-associated genes, yielding 147 common targets. Protein\u2013protein interaction analysis identified 134 interacting proteins and 590 interactions, with GABAA receptor subunits prominently represented among the top hub genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses further identified GABA-related functions and neuroactive ligand\u2013receptor signaling. Integration of compound\u2013target functional profiling with structural analysis prioritized the luteolin-derived flavonoid lineage, leading to the selection of orientin, a C-glycosylflavone constituent of P. incarnata, and luteolin, its structurally related core flavone scaffold, for experimental validation. In differentiated SH-SY5Y cells, pretreatment with orientin or luteolin attenuated L-glutamic acid-induced cellular injury in the presence of glycine, as evidenced by improved cell viability and reduced lactate dehydrogenase release. Both compounds also markedly reduced glutamate-induced intracellular Ca2+ accumulation. Notably, thapsigargin substantially reversed these Ca2+-lowering effects, suggesting a potential role for ER-associated Ca2+ regulatory mechanisms. The predicted GABAergic targets were not directly validated, and the cellular findings demonstrate neuroprotection against glutamate-induced excitotoxicity rather than direct GABAA receptor modulation or antiseizure efficacy. Collectively, these findings demonstrate the utility of network pharmacology-guided prioritization for identifying bioactive constituents of P. incarnata and support orientin as a neuroprotective candidate for further mechanistic and in vivo investigation.<\/jats:p>","DOI":"10.3390\/ijms27198605","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:40:13Z","timestamp":1790358013000},"page":"8605","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Network Pharmacology-Guided Identification of Orientin from Passiflora incarnata Reveals Neuroprotective Effects Against Glutamate-Induced Excitotoxicity Through Regulation of Calcium Homeostasis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7662-5601","authenticated-orcid":false,"given":"Jinyoung","family":"Park","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Kangwon National University School of Medicine, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Muhammad","family":"Yasir","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Kangwon National University School of Medicine, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Eun-Taek","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Medical Environmental Biology and Tropical Medicine, Kangwon National University School of Medicine, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0836-6675","authenticated-orcid":false,"given":"Jin-Hee","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Medical Environmental Biology and Tropical Medicine, Kangwon National University School of Medicine, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Won Sun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Physiology, Kangwon National University School of Medicine, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0424-1667","authenticated-orcid":false,"given":"Jongseon","family":"Choe","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Kangwon National University School of Medicine, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1984-3545","authenticated-orcid":false,"given":"Wanjoo","family":"Chun","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Kangwon National University School of Medicine, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"107966","DOI":"10.1016\/j.neuropharm.2020.107966","article-title":"Mechanisms of action of currently used antiseizure drugs","volume":"168","author":"Sills","year":"2020","journal-title":"Neuropharmacology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/S1474-4422(23)00151-5","article-title":"Drug resistance in epilepsy","volume":"22","author":"Perucca","year":"2023","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1124\/pr.120.019539","article-title":"Drug Resistance in Epilepsy: Clinical Impact, Potential Mechanisms, and New Innovative Treatment Options","volume":"72","author":"Loscher","year":"2020","journal-title":"Pharmacol. Rev."},{"key":"ref_4","first-page":"161","article-title":"Advances and guidance in the treatment of drug-resistant epilepsy: A review by the Andalusian Epilepsy Society of the new drugs cenobamate, fenfluramine and cannabidiol","volume":"79","year":"2024","journal-title":"Rev. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"879","DOI":"10.2174\/011570159X323666241029171256","article-title":"Antiseizure Medications: Advancements, Challenges, and Prospects in Drug Development","volume":"23","author":"Ng","year":"2025","journal-title":"Curr. Neuropharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1111\/epi.18305","article-title":"Epilepsy medication management: Addressing common treatment barriers to adopting cenobamate and other new antiseizure medications","volume":"66","author":"Rosenfeld","year":"2025","journal-title":"Epilepsia"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1146\/annurev-med-050522-034458","article-title":"Advances in Therapy for Refractory Epilepsy","volume":"76","author":"Jehi","year":"2025","journal-title":"Annu. Rev. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1007\/s40263-024-01130-y","article-title":"Recent Advances in Pharmacologic Treatments of Drug-Resistant Epilepsy: Breakthrough in Sight","volume":"38","author":"Klein","year":"2024","journal-title":"CNS Drugs"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"De Bellis, M., d\u2019Orsi, G., Rubino, E.M., Arigliano, C., Carella, M., Sciruicchio, V., Liantonio, A., De Luca, A., and Imbrici, P. (2025). Adverse effects of antiseizure medications: A review of the impact of pharmacogenetics and drugs interactions in clinical practice. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1584566"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1002\/epd2.20069","article-title":"Pharmacological aspects of antiseizure medications: From basic mechanisms to clinical considerations of drug interactions and use of therapeutic drug monitoring","volume":"25","author":"Eyal","year":"2023","journal-title":"Epileptic Disord."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1007\/s40263-023-01013-8","article-title":"Adverse Event Profiles of Antiseizure Medications and the Impact of Coadministration on Drug Tolerability in Adults with Epilepsy","volume":"37","author":"Willems","year":"2023","journal-title":"CNS Drugs"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1212\/CON.0000000000001081","article-title":"Approach to the Medical Treatment of Epilepsy","volume":"28","author":"Brigo","year":"2022","journal-title":"Continuum"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"110970","DOI":"10.1016\/j.yebeh.2026.110970","article-title":"Novel epilepsy treatments in clinical development","volume":"179","author":"Mesraoua","year":"2026","journal-title":"Epilepsy Behav."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/s41573-020-00114-z","article-title":"Natural products in drug discovery: Advances and opportunities","volume":"20","author":"Atanasov","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Janda, K., Wojtkowska, K., Jakubczyk, K., Antoniewicz, J., and Skonieczna-Zydecka, K. (2020). Passiflora incarnata in Neuropsychiatric Disorders-A Systematic Review. Nutrients, 12.","DOI":"10.3390\/nu12123894"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/j.jep.2013.09.047","article-title":"Passiflora incarnata L.: Ethnopharmacology, clinical application, safety and evaluation of clinical trials","volume":"150","author":"Miroddi","year":"2013","journal-title":"J. Ethnopharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1002\/ptr.3352","article-title":"Modulation of the gamma-aminobutyric acid (GABA) system by Passiflora incarnata L.","volume":"25","author":"Appel","year":"2011","journal-title":"Phytother. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1016\/j.phymed.2010.03.002","article-title":"Passiflora incarnata L. (Passionflower) extracts elicit GABA currents in hippocampal neurons in vitro, and show anxiogenic and anticonvulsant effects in vivo, varying with extraction method","volume":"17","author":"Elsas","year":"2010","journal-title":"Phytomedicine"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.jep.2011.11.011","article-title":"Dual protective effect of Passiflora incarnata in epilepsy and associated post-ictal depression","volume":"139","author":"Singh","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Nassiri-Asl, M., Shariati-Rad, S., and Zamansoltani, F. (2007). Anticonvulsant effects of aerial parts of Passiflora incarnata extract in mice: Involvement of benzodiazepine and opioid receptors. BMC Complement. Altern. Med., 7.","DOI":"10.1186\/1472-6882-7-26"},{"key":"ref_21","first-page":"6598434","article-title":"Herbal Medicinal Products from Passiflora for Anxiety: An Unexploited Potential","volume":"2020","author":"Rodrigues","year":"2020","journal-title":"ScientificWorldJournal"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Noor, F., Tahir Ul Qamar, M., Ashfaq, U.A., Albutti, A., Alwashmi, A.S.S., and Aljasir, M.A. (2022). Network Pharmacology Approach for Medicinal Plants: Review and Assessment. Pharmaceuticals, 15.","DOI":"10.3390\/ph15050572"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"103836","DOI":"10.1016\/j.autrev.2025.103836","article-title":"Integrating network pharmacology and experimental validation to advance psoriasis treatment: Multi-target mechanistic elucidation of medicinal herbs and natural compounds","volume":"24","author":"Jo","year":"2025","journal-title":"Autoimmun. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1055\/s-0028-1088322","article-title":"Anxiolytic activity of a phytochemically characterized Passiflora incarnata extract is mediated via the GABAergic system","volume":"74","author":"Grundmann","year":"2008","journal-title":"Planta Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/S0378-8741(97)00042-1","article-title":"Behavioural effects of Passiflora incarnata L. and its indole alkaloid and flavonoid derivatives and maltol in the mouse","volume":"57","author":"Soulimani","year":"1997","journal-title":"J. Ethnopharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2582","DOI":"10.2174\/1381612826666200526150113","article-title":"Extracts and Flavonoids of Passiflora Species as Promising Anti-inflammatory and Antioxidant Substances","volume":"27","author":"Ozarowski","year":"2021","journal-title":"Curr. Pharm. Des."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/nchembio.118","article-title":"Network pharmacology: The next paradigm in drug discovery","volume":"4","author":"Hopkins","year":"2008","journal-title":"Nat. Chem. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"110","DOI":"10.3724\/SP.J.1009.2013.00110","article-title":"Traditional Chinese medicine network pharmacology: Theory, methodology and application","volume":"11","author":"Li","year":"2013","journal-title":"Chin. J. Nat. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"bbad518","DOI":"10.1093\/bib\/bbad518","article-title":"Network pharmacology: Towards the artificial intelligence-based precision traditional Chinese medicine","volume":"25","author":"Zhang","year":"2023","journal-title":"Brief. Bioinform."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Panossian, A. (2025). Trends and Pitfalls in the Progress of Network Pharmacology Research on Natural Products. Pharmaceuticals, 18.","DOI":"10.3390\/ph18040538"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Wang, X., Hu, Y., Zhou, X., and Li, S. (2022). Editorial: Network pharmacology and traditional medicine: Setting the new standards by combining In silico and experimental work. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1002537"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/S0143-4160(03)00141-6","article-title":"Molecular mechanisms of calcium-dependent neurodegeneration in excitotoxicity","volume":"34","author":"Arundine","year":"2003","journal-title":"Cell Calcium"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"114786","DOI":"10.1016\/j.bcp.2021.114786","article-title":"Role of glutamate excitotoxicity and glutamate transporter EAAT2 in epilepsy: Opportunities for novel therapeutics development","volume":"193","author":"Green","year":"2021","journal-title":"Biochem. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"a022863","DOI":"10.1101\/cshperspect.a022863","article-title":"Glutamatergic Mechanisms Associated with Seizures and Epilepsy","volume":"5","author":"White","year":"2015","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Chen, T.S., Huang, T.H., Lai, M.C., and Huang, C.W. (2023). The Role of Glutamate Receptors in Epilepsy. Biomedicines, 11.","DOI":"10.3390\/biomedicines11030783"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3129","DOI":"10.1038\/s41401-025-01576-w","article-title":"Molecular mechanisms of excitotoxicity and their relevance to the pathogenesis of neurodegenerative diseases\u2014An update","volume":"46","author":"Wu","year":"2025","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/aps.2009.24","article-title":"Molecular mechanisms of excitotoxicity and their relevance to pathogenesis of neurodegenerative diseases","volume":"30","author":"Dong","year":"2009","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.seizure.2022.11.007","article-title":"Intracellular calcium homeostasis and its dysregulation underlying epileptic seizures","volume":"103","author":"Zhou","year":"2022","journal-title":"Seizure"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1038\/nrn1430","article-title":"The neurobiology of antiepileptic drugs","volume":"5","author":"Rogawski","year":"2004","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Mao, X.Y., Zhou, H.H., and Jin, W.L. (2019). Redox-Related Neuronal Death and Crosstalk as Drug Targets: Focus on Epilepsy. Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.00512"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s40035-021-00278-7","article-title":"Excitotoxicity, calcium and mitochondria: A triad in synaptic neurodegeneration","volume":"11","author":"Verma","year":"2022","journal-title":"Transl. Neurodegener."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Kritis, A.A., Stamoula, E.G., Paniskaki, K.A., and Vavilis, T.D. (2015). Researching glutamate-induced cytotoxicity in different cell lines: A comparative\/collective analysis\/study. Front. Cell. Neurosci., 9.","DOI":"10.3389\/fncel.2015.00091"},{"key":"ref_43","first-page":"293689","article-title":"Oxidative stress associated with neuronal apoptosis in experimental models of epilepsy","volume":"2014","author":"Gomez","year":"2014","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"113376","DOI":"10.1016\/j.fct.2022.113376","article-title":"Heterocyclic aromatic amines induce Neuro-2a cells cytotoxicity through oxidative stress-mediated mitochondria-dependent apoptotic signals","volume":"168","author":"Feng","year":"2022","journal-title":"Food Chem. Toxicol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4608","DOI":"10.1007\/s12035-020-02050-w","article-title":"Human CYP2D6 in the Brain Is Protective Against Harmine-Induced Neurotoxicity: Evidence from Humanized CYP2D6 Transgenic Mice","volume":"57","author":"Stocco","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"7707","DOI":"10.1038\/s41598-024-57824-2","article-title":"Neuroprotective mechanisms of luteolin in glutamate-induced oxidative stress and autophagy-mediated neuronal cell death","volume":"14","author":"Vongthip","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1177\/1535370217737983","article-title":"Neuroprotective effects of orientin on oxygen-glucose deprivation\/reperfusion-induced cell injury in primary culture of rat cortical neurons","volume":"243","author":"Tian","year":"2018","journal-title":"Exp. Biol. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1038\/325529a0","article-title":"Glycine potentiates the NMDA response in cultured mouse brain neurons","volume":"325","author":"Johnson","year":"1987","journal-title":"Nature"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S0006-8993(99)01995-2","article-title":"Emergence of excitotoxicity in cultured forebrain neurons coincides with larger glutamate-stimulated [Ca2+]i increases and NMDA receptor mRNA levels","volume":"849","author":"Cheng","year":"1999","journal-title":"Brain Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/19\/8605\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T04:14:27Z","timestamp":1790482467000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/19\/8605"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,25]]},"references-count":49,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["ijms27198605"],"URL":"https:\/\/doi.org\/10.3390\/ijms27198605","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,25]]}}}