{"id":"0f404d42-51dd-596d-9e30-7d8947b0d5fb","stable_key":"7484635e-cc8f-5cd6-a978-6dc5775a7db5:berberine-metformin-rat-slc22a2","predicate":"inhibits_metformin_transport_by","statement":"Berberine inhibited rat OCT2-mediated metformin uptake in transfected cells, with reported IC50 11.3 micromolar.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"96ecb278-9679-5fa1-8dd5-14cd65e2e356","mechanism_event_label":"Transport inhibition is a distinct interaction mechanism from liver CYP inhibition.","subject":{"id":"7bbe0633-b2f1-510f-adc0-3c4d0ddad05d","slug":"berberine","display_name":"Berberine","entity_type_key":"small_molecule"},"object":{"id":"665ab09e-07ce-51e1-bfac-0cdd2763e290","slug":"rat-slc22a2","display_name":"Rat organic cation transporter 2 / Oct2","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"96ecb278-9679-5fa1-8dd5-14cd65e2e356","stable_key":"7484635e-cc8f-5cd6-a978-6dc5775a7db5:berberine-metformin-rat-slc22a2-event","event_type":"biochemical_relationship","label":"Transport inhibition is a distinct interaction mechanism from liver CYP inhibition.","description":"Berberine inhibited rat OCT2-mediated metformin uptake in transfected cells, with reported IC50 11.3 micromolar.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"519971b1-5aef-5ad7-8022-840144855cd0","slug":"metformin","display_name":"Metformin","entity_type_key":"drug"},"role":"assayed_substrate","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"7bbe0633-b2f1-510f-adc0-3c4d0ddad05d","slug":"berberine","display_name":"Berberine","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"665ab09e-07ce-51e1-bfac-0cdd2763e290","slug":"rat-slc22a2","display_name":"Rat organic cation transporter 2 / Oct2","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/berberine-research/25359200.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"e46385d733a3c5fc9c39b89a27ef7ca62d228258ae47bb605c6a86eca68ee8db\", \"start_char\": 0, \"end_char\": 1353, \"text_sha256\": \"e46385d733a3c5fc9c39b89a27ef7ca62d228258ae47bb605c6a86eca68ee8db\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Transporter-expressing cells and intravenous rat pharmacokinetics","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Intravenous metformin 2 mg/kg and berberine 10 mg/kg in rats; in-vitro concentration-response","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"HEK293 is the host cell, not proof that the expressed transporter is human; the indexed proteins are rat Slc22a1/Slc22a2. Intravenous rat results cannot determine an oral human interaction. Assayed substrate was metformin, not thiamine.","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":"Rat OCT1/2 in HEK293 cells and rats; rat protein identity indexed in primary-publication chemical records","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Transport inhibition is a distinct interaction mechanism from liver CYP inhibition.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[berberine-p25359200] Organic cation transporter-mediated drug-drug interaction potential between berberine and metformin. (2015). https://pubmed.ncbi.nlm.nih.gov/25359200/ DOI: 10.1007/s12272-014-0510-6","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Metformin uptake and disposition","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"60ee71cc-70eb-5dd1-aa85-208d559f66c6","evidence_kind":"source_excerpt","locator":"Lines 779-790","start_line":779,"end_line":790,"excerpt":"### berberine-metformin-rat-slc22a2\nBerberine inhibited rat OCT2-mediated metformin uptake in transfected cells, with reported IC50 11.3 micromolar.\nCondition category: normal\nnutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Transport inhibition is a distinct interaction mechanism from liver CYP inhibition.\norganism: Rat OCT1/2 in HEK293 cells and rats; rat protein identity indexed in primary-publication chemical records\ntissue_or_cell_type: Metformin uptake and disposition\nexperimental_model: Transporter-expressing cells and intravenous rat pharmacokinetics\nlimitations: HEK293 is the host cell, not proof that the expressed transporter is human; the indexed proteins are rat Slc22a1/Slc22a2. Intravenous rat results cannot determine an oral human interaction. Assayed substrate was metformin, not thiamine.\nexposure: Intravenous metformin 2 mg/kg and berberine 10 mg/kg in rats; in-vitro concentration-response\nevidence_span: {\"source_cache\": \"artifacts/berberine-research/25359200.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"e46385d733a3c5fc9c39b89a27ef7ca62d228258ae47bb605c6a86eca68ee8db\", \"start_char\": 0, \"end_char\": 1353, \"text_sha256\": \"e46385d733a3c5fc9c39b89a27ef7ca62d228258ae47bb605c6a86eca68ee8db\"}\n[berberine-p25359200] Organic cation transporter-mediated drug-drug interaction potential between berberine and metformin. (2015). https://pubmed.ncbi.nlm.nih.gov/25359200/ DOI: 10.1007/s12272-014-0510-6","model_system":"Transporter-expressing cells and intravenous rat pharmacokinetics","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [berberine-p25359200] Organic cation transporter-mediated drug-drug interaction potential between berberine and metformin. (2015). https://pubmed.ncbi.nlm.nih.gov/25359200/ DOI: 10.1007/s12272-014-0510-6","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"9bb61e1d-e5cf-5b05-a9ca-409291f7a313","stable_key":"import-7484635e-cc8f-5cd6-a978-6dc5775a7db5","title":"Berberine: metabolism, nutrient connections 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. 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