{"id":"6cead739-9c1f-53a0-a77d-2cf220154ac0","stable_key":"74ef5bba-ee14-531c-b1bf-d1f297c56bb6:fisetin-cross-species-plasma","predicate":"impairs","statement":"Old-mouse plasma reduced NO-related bioactivity and increased mitochondrial oxidative stress in cultured human aortic endothelial cells; fisetin treatment of donor mice attenuated these effects.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"c7498394-118b-59b6-9f4d-3af8b6152da0","mechanism_event_label":"A plasma-transfer experiment tested effects on recipient cells.","subject":{"id":"ef37d030-70ae-5754-b90e-cd7351f9de6d","slug":"old-mouse-plasma-sasp","display_name":"Old-mouse circulating secretory milieu","entity_type_key":"cellular_process"},"object":{"id":"a38a4796-1892-503c-88fd-50ad8e9a566a","slug":"human-aortic-cell-no-after-mouse-plasma","display_name":"Nitric-oxide bioactivity in human aortic endothelial cells exposed to mouse plasma","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"c7498394-118b-59b6-9f4d-3af8b6152da0","stable_key":"74ef5bba-ee14-531c-b1bf-d1f297c56bb6:fisetin-cross-species-plasma-event","event_type":"observed_relationship","label":"A plasma-transfer experiment tested effects on recipient cells.","description":"Old-mouse plasma reduced NO-related bioactivity and increased mitochondrial oxidative stress in cultured human aortic endothelial cells; fisetin treatment of donor mice attenuated these effects.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"ef37d030-70ae-5754-b90e-cd7351f9de6d","slug":"old-mouse-plasma-sasp","display_name":"Old-mouse circulating secretory milieu","entity_type_key":"cellular_process"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"a38a4796-1892-503c-88fd-50ad8e9a566a","slug":"human-aortic-cell-no-after-mouse-plasma","display_name":"Nitric-oxide bioactivity in human aortic endothelial cells exposed to mouse plasma","entity_type_key":"cellular_process"},"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":"563d0083-0065-5949-a288-9c8283864e0c","slug":"mouse-cxcl12","display_name":"Mouse chemokine CXCL12","entity_type_key":"cytokine"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"f2a6b7ab-ad41-5ada-8895-41d6ce42f4e4","slug":"nitric-oxide","display_name":"NO","entity_type_key":"small_molecule"},"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":"Mouse plasma applied to human endothelial culture.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Cross-species ex vivo experiment, not human oral fisetin exposure.","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":"A plasma-transfer experiment tested effects on recipient cells.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Senolytic Treatment With Fisetin Reverses Age-Related Endothelial Dysfunction Partially Mediated by SASP Factor CXCL12. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42021544/ · DOI 10.1111/acel.70500","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"855b00a2-c49e-5bba-8e77-1a23efbeddde","evidence_kind":"source_excerpt","locator":"Lines 264-270","start_line":264,"end_line":270,"excerpt":"## fisetin-cross-species-plasma\nA plasma-transfer experiment tested effects on recipient cells.\nOld-mouse plasma reduced NO-related bioactivity and increased mitochondrial oxidative stress in cultured human aortic endothelial cells; fisetin treatment of donor mice attenuated these effects.\nModel: Mouse plasma applied to human endothelial culture.\nLimitations: Cross-species ex vivo experiment, not human oral fisetin exposure.\nEvidence access: Primary abstract\nSenolytic Treatment With Fisetin Reverses Age-Related Endothelial Dysfunction Partially Mediated by SASP Factor CXCL12. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42021544/ · DOI 10.1111/acel.70500","model_system":"Mouse plasma applied to human endothelial culture.","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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