{"id":"649c3e02-63e9-5e85-a64e-70227a28cc8d","stable_key":"74ef5bba-ee14-531c-b1bf-d1f297c56bb6:fisetin-sirt1-foxo-response","predicate":"increases_expression","statement":"The THP-1 treatments increased SIRT1 and FOXO3a expression while suppressing high-glucose inflammatory responses.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"507a4255-5fb2-5bc0-aa40-d5f6ed586a21","mechanism_event_label":"This branch connects to NAD-dependent cell regulation.","subject":{"id":"dee05061-c3f3-5226-8054-dd58b76a585d","slug":"fisetin","display_name":"Fisetin","entity_type_key":"small_molecule"},"object":{"id":"b8e1bfa9-c412-5f35-97af-cfc722123d27","slug":"sirt1","display_name":"SIRT1","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"507a4255-5fb2-5bc0-aa40-d5f6ed586a21","stable_key":"74ef5bba-ee14-531c-b1bf-d1f297c56bb6:fisetin-sirt1-foxo-response-event","event_type":"observed_relationship","label":"This branch connects to NAD-dependent cell regulation.","description":"The THP-1 treatments increased SIRT1 and FOXO3a expression while suppressing high-glucose inflammatory responses.","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":"b8e1bfa9-c412-5f35-97af-cfc722123d27","slug":"sirt1","display_name":"SIRT1","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"80472c4b-ecc2-52e3-a766-f8463294774f","slug":"luteolin","display_name":"Luteolin / 3′,4′,5,7-tetrahydroxyflavone","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"b3582cc3-0cdb-5d93-87e0-c3651f60d6fa","slug":"foxo3","display_name":"Human FOXO3","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Fisetin, luteolin and combination conditions in human cells.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Expression is not proven direct SIRT1 activation or greater NAD availability.","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":"This branch connects to NAD-dependent cell regulation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Combination Treatments with Luteolin and Fisetin Enhance Anti-Inflammatory Effects in High Glucose-Treated THP-1 Cells Through Histone Acetyltransferase/Histone Deacetylase Regulation. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28650731/ · DOI 10.1089/jmf.2017.3968","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"21478e53-a8ed-5b88-ab02-4d47886cb2a8","evidence_kind":"source_excerpt","locator":"Lines 456-462","start_line":456,"end_line":462,"excerpt":"## fisetin-sirt1-foxo-response\nThis branch connects to NAD-dependent cell regulation.\nThe THP-1 treatments increased SIRT1 and FOXO3a expression while suppressing high-glucose inflammatory responses.\nModel: Fisetin, luteolin and combination conditions in human cells.\nLimitations: Expression is not proven direct SIRT1 activation or greater NAD availability.\nEvidence access: Primary abstract\nCombination Treatments with Luteolin and Fisetin Enhance Anti-Inflammatory Effects in High Glucose-Treated THP-1 Cells Through Histone Acetyltransferase/Histone Deacetylase Regulation. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28650731/ · DOI 10.1089/jmf.2017.3968","model_system":"Fisetin, luteolin and combination conditions in human 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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