{"id":"5682ea59-0817-5d4f-97e4-f742f11572ed","stable_key":"74ef5bba-ee14-531c-b1bf-d1f297c56bb6:fisetin-iron-signaling-antagonism","predicate":"reduces_fisetin_induction_of","statement":"In mouse HT22 cells, added iron reduced fisetin-induced nuclear Nrf2 and ATF4 from an iron:fisetin ratio of 0.5:1; copper did not do so in the tested range.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"ec51d7c3-9151-5b8c-afb2-44489675a5c3","mechanism_event_label":"Iron weakened the signaling response under these conditions.","subject":{"id":"59d6d1cd-df32-5b58-b950-3188bc7b95d6","slug":"iron-ii","display_name":"Ferrous iron","entity_type_key":"ion"},"object":{"id":"95319607-3946-51b3-8235-400ec3223692","slug":"mouse-nfe2l2","display_name":"Mouse Nrf2 / Nfe2l2","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"ec51d7c3-9151-5b8c-afb2-44489675a5c3","stable_key":"74ef5bba-ee14-531c-b1bf-d1f297c56bb6:fisetin-iron-signaling-antagonism-event","event_type":"observed_relationship","label":"Iron weakened the signaling response under these conditions.","description":"In mouse HT22 cells, added iron reduced fisetin-induced nuclear Nrf2 and ATF4 from an iron:fisetin ratio of 0.5:1; copper did not do so in the tested range.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"59d6d1cd-df32-5b58-b950-3188bc7b95d6","slug":"iron-ii","display_name":"Ferrous iron","entity_type_key":"ion"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"95319607-3946-51b3-8235-400ec3223692","slug":"mouse-nfe2l2","display_name":"Mouse Nrf2 / Nfe2l2","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"dee05061-c3f3-5226-8054-dd58b76a585d","slug":"fisetin","display_name":"Fisetin","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"7a0fa32a-a00f-5500-bce7-8e8d101a8e2b","slug":"mouse-atf4","display_name":"Mouse activating transcription factor 4 / Atf4","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"2a870bb5-05a0-5e51-a70c-a9a843a8b571","slug":"copper-ii","display_name":"Copper(II) ion","entity_type_key":"ion"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"5 micromolar fisetin with FeCl2/CuCl2 titration.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Cell-culture ratio, not a clinical spacing rule for supplements.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Fisetin collection; molecular form, preparation, species, exposure and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"fisetin","display_name":"Fisetin","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Iron weakened the signaling response under these conditions.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Modulation of the Neuroprotective and Anti-inflammatory Activities of the Flavonol Fisetin by the Transition Metals Iron and Copper. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33187316/ · DOI 10.3390/antiox9111113","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"b4525df9-dba4-5635-bd9a-7f7e3d472718","evidence_kind":"source_excerpt","locator":"Lines 160-166","start_line":160,"end_line":166,"excerpt":"## fisetin-iron-signaling-antagonism\nIron weakened the signaling response under these conditions.\nIn mouse HT22 cells, added iron reduced fisetin-induced nuclear Nrf2 and ATF4 from an iron:fisetin ratio of 0.5:1; copper did not do so in the tested range.\nModel: 5 micromolar fisetin with FeCl2/CuCl2 titration.\nLimitations: Cell-culture ratio, not a clinical spacing rule for supplements.\nEvidence access: Primary full text\nModulation of the Neuroprotective and Anti-inflammatory Activities of the Flavonol Fisetin by the Transition Metals Iron and Copper. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33187316/ · DOI 10.3390/antiox9111113","model_system":"5 micromolar fisetin with FeCl2/CuCl2 titration.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"1108bfff-6504-5152-a51f-ff3d7c27c282","stable_key":"import-74ef5bba-ee14-531c-b1bf-d1f297c56bb6","title":"Fisetin: metabolism, cell-state responses and cross-nutrient mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text.","file_path":"","sha256":"c30e0764cd34bd062cfcbfaf32357ef29dfda30e7d4153c545178140f5054e09","revision_id":"40ff52c0-f4b9-5820-8abb-ff002c6364a4","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}