{"id":"570418b9-006a-5d02-a496-c5b412111089","stable_key":"74ef5bba-ee14-531c-b1bf-d1f297c56bb6:fisetin-luteolin-combination","predicate":"combined_with","statement":"In high-glucose-treated human THP-1 cells, 500 nM fisetin plus 500 nM or 1 micromolar luteolin suppressed inflammatory output.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"ad1b598e-0a6b-5be6-9c87-8f5bb7a7111c","mechanism_event_label":"Two compounds were actually tested together.","subject":{"id":"dee05061-c3f3-5226-8054-dd58b76a585d","slug":"fisetin","display_name":"Fisetin","entity_type_key":"small_molecule"},"object":{"id":"80472c4b-ecc2-52e3-a766-f8463294774f","slug":"luteolin","display_name":"Luteolin / 3′,4′,5,7-tetrahydroxyflavone","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"ad1b598e-0a6b-5be6-9c87-8f5bb7a7111c","stable_key":"74ef5bba-ee14-531c-b1bf-d1f297c56bb6:fisetin-luteolin-combination-event","event_type":"observed_relationship","label":"Two compounds were actually tested together.","description":"In high-glucose-treated human THP-1 cells, 500 nM fisetin plus 500 nM or 1 micromolar luteolin suppressed inflammatory output.","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":"80472c4b-ecc2-52e3-a766-f8463294774f","slug":"luteolin","display_name":"Luteolin / 3′,4′,5,7-tetrahydroxyflavone","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"875a94da-1eee-50d2-b5c1-e4316c2a8f45","slug":"nf-kappab-signaling","display_name":"NF-kappa-B signaling","entity_type_key":"cellular_process"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"20 mM glucose for 48 hours with osmotic and normoglycemic controls.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Combination activity is not demonstrated clinical synergy; assess interaction statistics before claiming more-than-additive benefit.","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":"Two compounds were actually tested together.","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":"7e3d98a5-6dcf-59ab-b048-8400bd43f5f0","evidence_kind":"source_excerpt","locator":"Lines 440-446","start_line":440,"end_line":446,"excerpt":"## fisetin-luteolin-combination\nTwo compounds were actually tested together.\nIn high-glucose-treated human THP-1 cells, 500 nM fisetin plus 500 nM or 1 micromolar luteolin suppressed inflammatory output.\nModel: 20 mM glucose for 48 hours with osmotic and normoglycemic controls.\nLimitations: Combination activity is not demonstrated clinical synergy; assess interaction statistics before claiming more-than-additive benefit.\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":"20 mM glucose for 48 hours with osmotic and normoglycemic controls.","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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