{"id":"4735336d-3828-5b60-b1c5-a36661661b71","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-abcb1-efflux","predicate":"reduces_intracellular_accumulation_of","statement":"DIM reduced intracellular accumulation of the MDR1 substrate rhodamine 123 in the transport experiment.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"1ae9b1ba-4cc1-5d14-929f-e7c76e21d809","mechanism_event_label":"A tracer supported increased efflux; it did not measure every drug.","subject":{"id":"6009bdd4-f1b5-5867-b5c3-cdf7c9645cd0","slug":"dim","display_name":"3,3'-Diindolylmethane / DIM","entity_type_key":"small_molecule"},"object":{"id":"3d400fcd-8b5b-5573-8c57-9066e8a83534","slug":"rhodamine-123","display_name":"Rhodamine 123","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"1ae9b1ba-4cc1-5d14-929f-e7c76e21d809","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-abcb1-efflux-event","event_type":"biochemical_relationship","label":"A tracer supported increased efflux; it did not measure every drug.","description":"DIM reduced intracellular accumulation of the MDR1 substrate rhodamine 123 in the transport experiment.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"c6139b52-4140-5622-9e33-1f6c6385265d","slug":"abcb1","display_name":"Human P-glycoprotein / ABCB1 / MDR1","entity_type_key":"protein"},"role":"implicated_transporter","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"6009bdd4-f1b5-5867-b5c3-cdf7c9645cd0","slug":"dim","display_name":"3,3'-Diindolylmethane / DIM","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"3d400fcd-8b5b-5573-8c57-9066e8a83534","slug":"rhodamine-123","display_name":"Rhodamine 123","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/dim-research/25542144.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d\", \"start_char\": 0, \"end_char\": 1440, \"text_sha256\": \"426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Promoter reporters, expression, knockdown and transport assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"DIM exposure with PXR inhibition or knockdown controls","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Cell-model induction, not a quantified human interaction. Older liver-slice assays showed little CYP3A4 response under their conditions.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"dim","display_name":"3,3'-Diindolylmethane / DIM","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human hepatocytes and intestinal cell models","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A tracer supported increased efflux; it did not measure every drug.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[dim-p25542144] Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. (2015). https://pubmed.ncbi.nlm.nih.gov/25542144/ DOI: 10.1016/j.toxlet.2014.12.015","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"PXR-regulated CYP3A4 and ABCB1","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"18047692-5fcf-53a8-82f2-f36d43c6dce6","evidence_kind":"source_excerpt","locator":"Lines 532-543","start_line":532,"end_line":543,"excerpt":"### dim-abcb1-efflux\nDIM reduced intracellular accumulation of the MDR1 substrate rhodamine 123 in the transport experiment.\nCondition category: normal\nnutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A tracer supported increased efflux; it did not measure every drug.\norganism: Human hepatocytes and intestinal cell models\ntissue_or_cell_type: PXR-regulated CYP3A4 and ABCB1\nexperimental_model: Promoter reporters, expression, knockdown and transport assays\nlimitations: Cell-model induction, not a quantified human interaction. Older liver-slice assays showed little CYP3A4 response under their conditions.\nexposure: DIM exposure with PXR inhibition or knockdown controls\nevidence_span: {\"source_cache\": \"artifacts/dim-research/25542144.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d\", \"start_char\": 0, \"end_char\": 1440, \"text_sha256\": \"426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d\"}\n[dim-p25542144] Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. (2015). https://pubmed.ncbi.nlm.nih.gov/25542144/ DOI: 10.1016/j.toxlet.2014.12.015","model_system":"Promoter reporters, expression, knockdown and transport assays","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [dim-p25542144] Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. (2015). https://pubmed.ncbi.nlm.nih.gov/25542144/ DOI: 10.1016/j.toxlet.2014.12.015","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"b6d70682-97f9-5893-a03c-f9f88836033c","stable_key":"import-182336c6-ed36-5ec6-8a09-25c31096262e","title":"Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"31e14060de904976d2f5d439f2bc9c8a99a72d34626c562c78429025e050d404","revision_id":"611094c1-a9cf-5b9b-b255-ac70b571696a","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}