{"id":"03959f33-62dd-5b92-b36d-8442bbe9f578","stable_key":"74ef5bba-ee14-531c-b1bf-d1f297c56bb6:fisetin-cardiac-nrf2","predicate":"increases_signaling","statement":"Fisetin increased SIRT1 and nuclear Nrf2-associated signaling in the rat cardiac study, with HO-1 and ferritin-heavy-chain expression changes.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"24621fab-9671-50a5-811f-6cac350c651f","mechanism_event_label":"Iron handling and antioxidant signaling were linked.","subject":{"id":"dee05061-c3f3-5226-8054-dd58b76a585d","slug":"fisetin","display_name":"Fisetin","entity_type_key":"small_molecule"},"object":{"id":"27636f1d-fd51-5697-a8bb-6c827f4f8b40","slug":"rat-nfe2l2","display_name":"Rat Nrf2 / Nfe2l2","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"24621fab-9671-50a5-811f-6cac350c651f","stable_key":"74ef5bba-ee14-531c-b1bf-d1f297c56bb6:fisetin-cardiac-nrf2-event","event_type":"observed_relationship","label":"Iron handling and antioxidant signaling were linked.","description":"Fisetin increased SIRT1 and nuclear Nrf2-associated signaling in the rat cardiac study, with HO-1 and ferritin-heavy-chain expression changes.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"dee05061-c3f3-5226-8054-dd58b76a585d","slug":"fisetin","display_name":"Fisetin","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"27636f1d-fd51-5697-a8bb-6c827f4f8b40","slug":"rat-nfe2l2","display_name":"Rat Nrf2 / Nfe2l2","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"46cd9ecc-a60b-592a-a095-9645baeb18a6","slug":"rat-sirt1","display_name":"Rat sirtuin 1 / Sirt1","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"c5f38746-6199-53e9-8b43-b42182419bea","slug":"rat-hmox1","display_name":"Rat heme oxygenase 1 / Hmox1","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"55599851-d8d1-51f7-b213-8be0f5f659e5","slug":"rat-fth1","display_name":"Rat ferritin heavy chain / Fth1","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Rat hearts and rat H9c2 cells.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Expression is not direct enzyme activation or proof of every transcriptional step.","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 handling and antioxidant signaling were linked.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Fisetin Attenuates Doxorubicin-Induced Cardiomyopathy In Vivo and In Vitro by Inhibiting Ferroptosis Through SIRT1/Nrf2 Signaling Pathway Activation. · 2021 · https://pubmed.ncbi.nlm.nih.gov/35273493/ · DOI 10.3389/fphar.2021.808480","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"8272b0ce-5e5d-5a83-9e99-d19b0d3b2189","evidence_kind":"source_excerpt","locator":"Lines 424-430","start_line":424,"end_line":430,"excerpt":"## fisetin-cardiac-nrf2\nIron handling and antioxidant signaling were linked.\nFisetin increased SIRT1 and nuclear Nrf2-associated signaling in the rat cardiac study, with HO-1 and ferritin-heavy-chain expression changes.\nModel: Rat hearts and rat H9c2 cells.\nLimitations: Expression is not direct enzyme activation or proof of every transcriptional step.\nEvidence access: Primary abstract\nFisetin Attenuates Doxorubicin-Induced Cardiomyopathy In Vivo and In Vitro by Inhibiting Ferroptosis Through SIRT1/Nrf2 Signaling Pathway Activation. · 2021 · https://pubmed.ncbi.nlm.nih.gov/35273493/ · DOI 10.3389/fphar.2021.808480","model_system":"Rat hearts and rat H9c2 cells.","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. 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