{"id":"21dba26b-004b-5aaa-ab6c-e29e85a5fc01","stable_key":"d8050016-13c9-5391-9d61-63de73590053:zeaxanthin-npc1l1-ester","predicate":"contributes_to","statement":"Ezetimibe-sensitive uptake also supported NPC1L1 involvement after dipalmitate exposure.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"9fd6788a-1afb-5d83-8f24-b049657ab8b6","mechanism_event_label":"The ester formulation also used the tested pathway.","subject":{"id":"9fbf0133-53c3-5ab1-8a95-4804d6115300","slug":"npc1l1","display_name":"Human Niemann-Pick C1-like protein 1 / NPC1L1","entity_type_key":"protein"},"object":{"id":"3c0b7157-7b95-5d6a-b201-ed8fa31e576b","slug":"intestinal-zeaxanthin-ester-uptake","display_name":"Zeaxanthin dipalmitate-associated uptake in intestinal epithelial models","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"9fd6788a-1afb-5d83-8f24-b049657ab8b6","stable_key":"d8050016-13c9-5391-9d61-63de73590053:zeaxanthin-npc1l1-ester-event","event_type":"biochemical_relationship","label":"The ester formulation also used the tested pathway.","description":"Ezetimibe-sensitive uptake also supported NPC1L1 involvement after dipalmitate exposure.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"c80509cf-412f-59ab-98c3-64da38c68028","slug":"zeaxanthin-dipalmitate","display_name":"Zeaxanthin dipalmitate","entity_type_key":"small_molecule"},"role":"supplied_form","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"9fbf0133-53c3-5ab1-8a95-4804d6115300","slug":"npc1l1","display_name":"Human Niemann-Pick C1-like protein 1 / NPC1L1","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"3c0b7157-7b95-5d6a-b201-ed8fa31e576b","slug":"intestinal-zeaxanthin-ester-uptake","display_name":"Zeaxanthin dipalmitate-associated uptake in intestinal epithelial models","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/zeaxanthin-research/42123990.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4\", \"start_char\": 0, \"end_char\": 1803, \"text_sha256\": \"c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Micelle uptake, transporter inhibition and protein-expression assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Free and dipalmitate xanthophyll micelles; BLT-1 and ezetimibe","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Inhibitors support pathway involvement rather than exclusivity. Protein-expression changes do not prove efflux; a cell model cannot establish clinical drug spacing.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"zeaxanthin","display_name":"Dietary (3R,3-prime-R)-zeaxanthin","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human Caco-2 monolayers","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The ester formulation also used the tested pathway.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[zeaxanthin-p42123990] Mechanisms of Cell Uptake and Transport of Xanthophylls in the Caco-2 Cell Model. (2026). https://pubmed.ncbi.nlm.nih.gov/42123990/ DOI: 10.3390/nu18091389","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Intestinal epithelial model","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"767accc5-fcc6-5cca-bd53-4617518d764c","evidence_kind":"source_excerpt","locator":"Lines 717-728","start_line":717,"end_line":728,"excerpt":"### zeaxanthin-npc1l1-ester\nEzetimibe-sensitive uptake also supported NPC1L1 involvement after dipalmitate exposure.\nCondition category: normal\nnutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The ester formulation also used the tested pathway.\norganism: Human Caco-2 monolayers\ntissue_or_cell_type: Intestinal epithelial model\nexperimental_model: Micelle uptake, transporter inhibition and protein-expression assays\nlimitations: Inhibitors support pathway involvement rather than exclusivity. Protein-expression changes do not prove efflux; a cell model cannot establish clinical drug spacing.\nexposure: Free and dipalmitate xanthophyll micelles; BLT-1 and ezetimibe\nevidence_span: {\"source_cache\": \"artifacts/zeaxanthin-research/42123990.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4\", \"start_char\": 0, \"end_char\": 1803, \"text_sha256\": \"c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4\"}\n[zeaxanthin-p42123990] Mechanisms of Cell Uptake and Transport of Xanthophylls in the Caco-2 Cell Model. (2026). https://pubmed.ncbi.nlm.nih.gov/42123990/ DOI: 10.3390/nu18091389","model_system":"Micelle uptake, transporter inhibition and protein-expression assays","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [zeaxanthin-p42123990] Mechanisms of Cell Uptake and Transport of Xanthophylls in the Caco-2 Cell Model. (2026). https://pubmed.ncbi.nlm.nih.gov/42123990/ DOI: 10.3390/nu18091389","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"df7effe5-d60c-525e-bd48-1518e1a03c51","stable_key":"import-d8050016-13c9-5391-9d61-63de73590053","title":"Zeaxanthin: metabolism, signaling and nutrient connections (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":"f872aef57169cee72edccda6652f3359e58cdf2e5427b507b83c32a9126ac7c1","revision_id":"dcd90b3a-8c34-57a8-999b-5ae1d2633943","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}