{"id":"bd84622e-1d8c-5d68-bf89-320e514163c9","stable_key":"ff370329-68a3-573d-96ee-597de78a3967:api-cyp3a4-inactivation","predicate":"decreases_in_recorded_comparison","statement":"Apigenin produced time-dependent CYP3A4 inactivation with reported KI 20.2 ± 12.7 micromolar and kinact 0.11 ± 0.04 per minute.","claim_class":"mechanistic","status":"source_recorded","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"cd4f0fcb-b61e-5cc1-94e4-b6b7e1bd7fab","mechanism_event_label":"Apigenin produced time-dependent CYP3A4 inactivation with reported KI 20.2 ± 12.7 micromolar and kinact 0.11 ± 0.04 per minute.","subject":{"id":"4425961f-4764-56d3-9887-87e47749379b","slug":"apigenin","display_name":"Apigenin","entity_type_key":"small_molecule"},"object":{"id":"54e95ff1-4ffa-5e6f-a4cb-b47e5d2a5bda","slug":"cyp3a4","display_name":"Human cytochrome P450 3A4","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"cd4f0fcb-b61e-5cc1-94e4-b6b7e1bd7fab","stable_key":"ff370329-68a3-573d-96ee-597de78a3967:api-cyp3a4-inactivation-event","event_type":"biochemical_relationship","label":"Apigenin produced time-dependent CYP3A4 inactivation with reported KI 20.2 ± 12.7 micromolar and kinact 0.11 ± 0.04 per minute.","description":"### api-cyp3a4-inactivation\n\nApigenin produced time-dependent CYP3A4 inactivation with reported KI 20.2 ± 12.7 micromolar and kinact 0.11 ± 0.04 per minute.\nThe proposed heme-adduct mechanism was not a directly identified covalent adduct structure.\nModel and exposure: Recombinant human CYP3A4; persistence after dialysis/oxidant challenge was investigated.\nLimitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.\nReference: Characterization of the CYP3A4 Enzyme Inhibition Potential of Selected Flavonoids. | 2021 | https://pubmed.ncbi.nlm.nih.gov/34069400/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC8158701/ | https://doi.org/10.3390/molecules26103018 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"4425961f-4764-56d3-9887-87e47749379b","slug":"apigenin","display_name":"Apigenin","entity_type_key":"small_molecule"},"role":"tested factor","stoichiometry":null,"state_label":"Apigenin preincubation","sequence_order":0,"notes":""},{"entity":{"id":"54e95ff1-4ffa-5e6f-a4cb-b47e5d2a5bda","slug":"cyp3a4","display_name":"Human cytochrome P450 3A4","entity_type_key":"protein"},"role":"measured outcome","stoichiometry":null,"state_label":"decrease","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_contrast","value_text":"{\"intervention\": \"Apigenin preincubation\", \"comparator\": \"Matched no-apigenin incubation\", \"endpoint\": \"Apigenin produced time-dependent CYP3A4 inactivation with reported KI 20.2 ± 12.7 micromolar and kinact 0.11 ± 0.04 per minute.\", \"effect_direction\": \"decrease\", \"combination\": \"single\", \"conditions\": []}","comparator":null,"unit":null,"notes":"Explicit extracted experimental comparison; recorded from source.","entity":null},{"dimension":"experimental_model","value_text":"Recombinant human CYP3A4; persistence after dialysis/oxidant challenge was investigated.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"interpretation_status","value_text":"Recorded from source with stated access limits; ungraded, not independent replication.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Apigenin collection; exact intervention and molecular form govern interpretation.","comparator":null,"unit":null,"notes":"","entity":{"slug":"apigenin","display_name":"Apigenin","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Apigenin produced time-dependent CYP3A4 inactivation with reported KI 20.2 ± 12.7 micromolar and kinact 0.11 ± 0.04 per minute.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Characterization of the CYP3A4 Enzyme Inhibition Potential of Selected Flavonoids. | https://pubmed.ncbi.nlm.nih.gov/34069400/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC8158701/ | https://doi.org/10.3390/molecules26103018","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"source_locator","value_text":"Reviewed reference api-cyp3a4-inactivation; The proposed heme-adduct mechanism was not a directly identified covalent adduct structure.","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"d268dc76-f551-53dd-be9f-c319188555df","evidence_kind":"source_excerpt","locator":"Lines 856-862","start_line":856,"end_line":862,"excerpt":"### api-cyp3a4-inactivation\n\nApigenin produced time-dependent CYP3A4 inactivation with reported KI 20.2 ± 12.7 micromolar and kinact 0.11 ± 0.04 per minute.\nThe proposed heme-adduct mechanism was not a directly identified covalent adduct structure.\nModel and exposure: Recombinant human CYP3A4; persistence after dialysis/oxidant challenge was investigated.\nLimitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.\nReference: Characterization of the CYP3A4 Enzyme Inhibition Potential of Selected Flavonoids. | 2021 | https://pubmed.ncbi.nlm.nih.gov/34069400/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC8158701/ | https://doi.org/10.3390/molecules26103018 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.","model_system":"Recombinant human CYP3A4; persistence after dialysis/oxidant challenge was investigated.","directness":"reported_statement","verification_status":"source_recorded","notes":"Original paraphrase in the retained reviewed reference, not a verbatim primary-paper quotation. Access level is explicit.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"54eac90b-add1-5f56-9036-d900307c5697","stable_key":"import-ff370329-68a3-573d-96ee-597de78a3967","title":"Apigenin: detailed mechanisms of action (reviewed 10 October 2026)","document_type":"imported_text","citation_label":"AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed.","file_path":"","sha256":"ede6e5c6b91d66b66844f2ff667a7f8303d9ac1281f15dc09db703f7de4da942","revision_id":"b41a39a2-0197-549c-97a5-1765e6696931","review_status":"source_recorded","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}