{"id":"65665575-b4cd-5960-bac4-b127b059005c","stable_key":"7484635e-cc8f-5cd6-a978-6dc5775a7db5:berberine-cyp2d6-sex","predicate":"poor_metabolizer_status_reduces_in_females","statement":"Female CYP2D6 poor metabolizers had an 80% lower M1-to-berberine ratio; the genotype effect was not found in males.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"92d53875-62fb-52c6-925c-d0efde5f9fc2","mechanism_event_label":"The metabolic effect of this gene variant depended on sex in this study.","subject":{"id":"10f7a103-d63d-5bf4-8384-c5e1308ce126","slug":"cyp2d6","display_name":"Human cytochrome P450 2D6","entity_type_key":"protein"},"object":{"id":"f2fda5e5-8f22-5c8a-ad77-956ba3b1e0af","slug":"berberine-m1-parent-ratio","display_name":"Berberine M1-to-parent metabolite ratio","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"92d53875-62fb-52c6-925c-d0efde5f9fc2","stable_key":"7484635e-cc8f-5cd6-a978-6dc5775a7db5:berberine-cyp2d6-sex-event","event_type":"observed_intervention","label":"The metabolic effect of this gene variant depended on sex in this study.","description":"Female CYP2D6 poor metabolizers had an 80% lower M1-to-berberine ratio; the genotype effect was not found in males.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"7bbe0633-b2f1-510f-adc0-3c4d0ddad05d","slug":"berberine","display_name":"Berberine","entity_type_key":"small_molecule"},"role":"parent","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"10f7a103-d63d-5bf4-8384-c5e1308ce126","slug":"cyp2d6","display_name":"Human cytochrome P450 2D6","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"f2fda5e5-8f22-5c8a-ad77-956ba3b1e0af","slug":"berberine-m1-parent-ratio","display_name":"Berberine M1-to-parent metabolite ratio","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/berberine-research/39488825.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"ba324da62a36391435595fd7c4de2a848aae714abd4df063433362e4fdddce33\", \"start_char\": 0, \"end_char\": 1787, \"text_sha256\": \"ba324da62a36391435595fd7c4de2a848aae714abd4df063433362e4fdddce33\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Transporter kinetics, mouse perfusion and human genotype-stratified pharmacokinetics","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Oral berberine; OCT1 and CYP2D6 functional variants; sex-stratified analysis","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Human OCT1 null finding differs from cellular and mouse findings. Sex-specific CYP2D6 result is not a universal rule for all formulations or a dosing algorithm.","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 participants and human OCT1; Oct1/2-deficient mice in separate arms","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The metabolic effect of this gene variant depended on sex in this study.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[berberine-p39488825] Sex-Dependent Effects of CYP2D6 on the Pharmacokinetics of Berberine in Humans. (2025). https://pubmed.ncbi.nlm.nih.gov/39488825/ DOI: 10.1002/cpt.3454","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Liver transport and systemic exposure","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"e2cf11dc-8b90-52af-9f91-d54165ce3b20","evidence_kind":"source_excerpt","locator":"Lines 272-283","start_line":272,"end_line":283,"excerpt":"### berberine-cyp2d6-sex\nFemale CYP2D6 poor metabolizers had an 80% lower M1-to-berberine ratio; the genotype effect was not found in males.\nCondition category: normal\nnutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The metabolic effect of this gene variant depended on sex in this study.\norganism: Human participants and human OCT1; Oct1/2-deficient mice in separate arms\ntissue_or_cell_type: Liver transport and systemic exposure\nexperimental_model: Transporter kinetics, mouse perfusion and human genotype-stratified pharmacokinetics\nlimitations: Human OCT1 null finding differs from cellular and mouse findings. Sex-specific CYP2D6 result is not a universal rule for all formulations or a dosing algorithm.\nexposure: Oral berberine; OCT1 and CYP2D6 functional variants; sex-stratified analysis\nevidence_span: {\"source_cache\": \"artifacts/berberine-research/39488825.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"ba324da62a36391435595fd7c4de2a848aae714abd4df063433362e4fdddce33\", \"start_char\": 0, \"end_char\": 1787, \"text_sha256\": \"ba324da62a36391435595fd7c4de2a848aae714abd4df063433362e4fdddce33\"}\n[berberine-p39488825] Sex-Dependent Effects of CYP2D6 on the Pharmacokinetics of Berberine in Humans. (2025). https://pubmed.ncbi.nlm.nih.gov/39488825/ DOI: 10.1002/cpt.3454","model_system":"Transporter kinetics, mouse perfusion and human genotype-stratified pharmacokinetics","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [berberine-p39488825] Sex-Dependent Effects of CYP2D6 on the Pharmacokinetics of Berberine in Humans. (2025). https://pubmed.ncbi.nlm.nih.gov/39488825/ DOI: 10.1002/cpt.3454","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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