{"id":"f4f949c5-07f2-51b1-b589-dcbdfea0726f","stable_key":"7484635e-cc8f-5cd6-a978-6dc5775a7db5:berberine-abcb1-efflux","predicate":"exports","statement":"OCT1/ABCB1 double-transfected cells transported berberine basolaterally to apically faster than single transfectants; zosuquidar inhibited apical efflux.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"5baab4b2-05ee-566d-b212-4e4824450adf","mechanism_event_label":"An entry transporter and an exit pump can work in sequence.","subject":{"id":"c6139b52-4140-5622-9e33-1f6c6385265d","slug":"abcb1","display_name":"Human P-glycoprotein / ABCB1 / MDR1","entity_type_key":"protein"},"object":{"id":"7bbe0633-b2f1-510f-adc0-3c4d0ddad05d","slug":"berberine","display_name":"Berberine","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"5baab4b2-05ee-566d-b212-4e4824450adf","stable_key":"7484635e-cc8f-5cd6-a978-6dc5775a7db5:berberine-abcb1-efflux-event","event_type":"biochemical_relationship","label":"An entry transporter and an exit pump can work in sequence.","description":"OCT1/ABCB1 double-transfected cells transported berberine basolaterally to apically faster than single transfectants; zosuquidar inhibited apical efflux.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"3cced77c-b044-5d97-8c81-4ff9ed3dd169","slug":"slc22a1","display_name":"Human organic cation transporter 1 / OCT1 / SLC22A1","entity_type_key":"protein"},"role":"uptake_partner","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"c6139b52-4140-5622-9e33-1f6c6385265d","slug":"abcb1","display_name":"Human P-glycoprotein / ABCB1 / MDR1","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"7bbe0633-b2f1-510f-adc0-3c4d0ddad05d","slug":"berberine","display_name":"Berberine","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/berberine-research/18157518.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"34651ed2e9ce3c38b6042e616b5c36d932fe6f1099c627d1b5403b338eae7b2b\", \"start_char\": 0, \"end_char\": 1918, \"text_sha256\": \"34651ed2e9ce3c38b6042e616b5c36d932fe6f1099c627d1b5403b338eae7b2b\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Polarized transporter-transfected MDCKII cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Berberine transport kinetics and transporter inhibition","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Engineered system, not direct evidence for human oral bioavailability or a universal transport bottleneck.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Berberine research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"berberine","display_name":"Berberine","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human OCT1, OCT2 and ABCB1 in engineered canine cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"An entry transporter and an exit pump can work in sequence.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[berberine-p18157518] Vectorial transport of the plant alkaloid berberine by double-transfected cells expressing the human organic cation transporter 1 (OCT1, SLC22A1) and the efflux pump MDR1 P-glycoprotein (ABCB1). (2008). https://pubmed.ncbi.nlm.nih.gov/18157518/ DOI: 10.1007/s00210-007-0219-x","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Basolateral uptake and apical export","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"transport_effect","value_text":"lowers","comparator":null,"unit":null,"notes":"Basolateral-to-apical flux exceeded absorptive flux and zosuquidar inhibited the apical efflux, so the step removes berberine from the cell.","entity":null},{"dimension":"transport_pool","value_text":"the enterocyte interior","comparator":null,"unit":null,"notes":"Basolateral-to-apical flux exceeded absorptive flux and zosuquidar inhibited the apical efflux, so the step removes berberine from the cell.","entity":null}],"evidence":[{"id":"56186b74-9bb2-5ede-b1d3-7dc992ea8f5a","evidence_kind":"source_excerpt","locator":"Lines 233-244","start_line":233,"end_line":244,"excerpt":"### berberine-abcb1-efflux\nOCT1/ABCB1 double-transfected cells transported berberine basolaterally to apically faster than single transfectants; zosuquidar inhibited apical efflux.\nCondition category: normal\nnutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: An entry transporter and an exit pump can work in sequence.\norganism: Human OCT1, OCT2 and ABCB1 in engineered canine cells\ntissue_or_cell_type: Basolateral uptake and apical export\nexperimental_model: Polarized transporter-transfected MDCKII cells\nlimitations: Engineered system, not direct evidence for human oral bioavailability or a universal transport bottleneck.\nexposure: Berberine transport kinetics and transporter inhibition\nevidence_span: {\"source_cache\": \"artifacts/berberine-research/18157518.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"34651ed2e9ce3c38b6042e616b5c36d932fe6f1099c627d1b5403b338eae7b2b\", \"start_char\": 0, \"end_char\": 1918, \"text_sha256\": \"34651ed2e9ce3c38b6042e616b5c36d932fe6f1099c627d1b5403b338eae7b2b\"}\n[berberine-p18157518] Vectorial transport of the plant alkaloid berberine by double-transfected cells expressing the human organic cation transporter 1 (OCT1, SLC22A1) and the efflux pump MDR1 P-glycoprotein (ABCB1). 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