{"id":"cff4b6f7-01ba-51b1-a3aa-a0b58615c5a0","stable_key":"7484635e-cc8f-5cd6-a978-6dc5775a7db5:berberine-rat-metformin-rat-slc22a2","predicate":"inhibits_metformin_transport_by","statement":"Berberine inhibited rat OCT2-mediated metformin transport, with IC50 1.02 micromolar.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"8cdb0842-eadc-5244-a87a-fb19dffd52f6","mechanism_event_label":"This identifies the rat transporter independently, preserving species.","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":"8cdb0842-eadc-5244-a87a-fb19dffd52f6","stable_key":"7484635e-cc8f-5cd6-a978-6dc5775a7db5:berberine-rat-metformin-rat-slc22a2-event","event_type":"biochemical_relationship","label":"This identifies the rat transporter independently, preserving species.","description":"Berberine inhibited rat OCT2-mediated metformin transport, with IC50 1.02 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/30428337.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"d35cfbe70c74323ef13e51af7affae3f13a4ff7b80a1d278620b8ced217346d8\", \"start_char\": 0, \"end_char\": 1775, \"text_sha256\": \"d35cfbe70c74323ef13e51af7affae3f13a4ff7b80a1d278620b8ced217346d8\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Oral rat pharmacokinetics, intestinal sacs and rat-transporter-expressing cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Oral metformin/berberine coadministration; concentration-dependent transport assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Route differs from the intravenous rat study. Changes in plasma, kidney tissue and excretion are separate outcomes; not proof of improved human combination efficacy.","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":"Rats and recombinant rat OCT1, OCT2 and MATE1","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"This identifies the rat transporter independently, preserving species.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[berberine-p30428337] Organic cation transporter and multidrug and toxin extrusion 1 co-mediated interaction between metformin and berberine. (2019). https://pubmed.ncbi.nlm.nih.gov/30428337/ DOI: 10.1016/j.ejps.2018.11.010","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Intestinal uptake, kidney distribution and excretion","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"52e2d5b5-ef6e-5aaf-b29f-061920629494","evidence_kind":"source_excerpt","locator":"Lines 818-829","start_line":818,"end_line":829,"excerpt":"### berberine-rat-metformin-rat-slc22a2\nBerberine inhibited rat OCT2-mediated metformin transport, with IC50 1.02 micromolar.\nCondition category: normal\nnutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: This identifies the rat transporter independently, preserving species.\norganism: Rats and recombinant rat OCT1, OCT2 and MATE1\ntissue_or_cell_type: Intestinal uptake, kidney distribution and excretion\nexperimental_model: Oral rat pharmacokinetics, intestinal sacs and rat-transporter-expressing cells\nlimitations: Route differs from the intravenous rat study. Changes in plasma, kidney tissue and excretion are separate outcomes; not proof of improved human combination efficacy.\nexposure: Oral metformin/berberine coadministration; concentration-dependent transport assays\nevidence_span: {\"source_cache\": \"artifacts/berberine-research/30428337.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"d35cfbe70c74323ef13e51af7affae3f13a4ff7b80a1d278620b8ced217346d8\", \"start_char\": 0, \"end_char\": 1775, \"text_sha256\": \"d35cfbe70c74323ef13e51af7affae3f13a4ff7b80a1d278620b8ced217346d8\"}\n[berberine-p30428337] Organic cation transporter and multidrug and toxin extrusion 1 co-mediated interaction between metformin and berberine. (2019). https://pubmed.ncbi.nlm.nih.gov/30428337/ DOI: 10.1016/j.ejps.2018.11.010","model_system":"Oral rat pharmacokinetics, intestinal sacs and rat-transporter-expressing cells","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [berberine-p30428337] Organic cation transporter and multidrug and toxin extrusion 1 co-mediated interaction between metformin and berberine. (2019). https://pubmed.ncbi.nlm.nih.gov/30428337/ DOI: 10.1016/j.ejps.2018.11.010","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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