{"id":"a7046325-8140-5405-bd31-672a48e043f3","stable_key":"7484635e-cc8f-5cd6-a978-6dc5775a7db5:berberine-human-cyp-3a4","predicate":"changes_probe_readout_for","statement":"Repeated berberine inhibited CYP3A4 phenotypic activity, with midazolam oral clearance reduced by 27%.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"0d97651f-0ab6-5c1d-8c8d-d91d85579a27","mechanism_event_label":"Drug clearance was measured, rather than inferred from gene expression.","subject":{"id":"7bbe0633-b2f1-510f-adc0-3c4d0ddad05d","slug":"berberine","display_name":"Berberine","entity_type_key":"small_molecule"},"object":{"id":"ed6c442f-f48e-5079-b26f-0e4c3e97797e","slug":"cyp3a4-phenotypic-activity","display_name":"CYP3A4 activity measured by probe-drug phenotyping","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"0d97651f-0ab6-5c1d-8c8d-d91d85579a27","stable_key":"7484635e-cc8f-5cd6-a978-6dc5775a7db5:berberine-human-cyp-3a4-event","event_type":"observed_intervention","label":"Drug clearance was measured, rather than inferred from gene expression.","description":"Repeated berberine inhibited CYP3A4 phenotypic activity, with midazolam oral clearance reduced by 27%.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"54e95ff1-4ffa-5e6f-a4cb-b47e5d2a5bda","slug":"cyp3a4","display_name":"Human cytochrome P450 3A4","entity_type_key":"protein"},"role":"phenotyped_enzyme","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"4d9e7b2e-8a2e-59e2-b3e1-35d8155334d5","slug":"midazolam","display_name":"Midazolam","entity_type_key":"small_molecule"},"role":"probe_drug","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":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"ed6c442f-f48e-5079-b26f-0e4c3e97797e","slug":"cyp3a4-phenotypic-activity","display_name":"CYP3A4 activity measured by probe-drug phenotyping","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/berberine-research/21870106.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"12e465c3c0a8ce995697a6fb9bf77c079e38b413e82c8b4f2a82e45a3dbf8ae5\", \"start_char\": 0, \"end_char\": 1817, \"text_sha256\": \"12e465c3c0a8ce995697a6fb9bf77c079e38b413e82c8b4f2a82e45a3dbf8ae5\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Two-phase randomized crossover enzyme-phenotyping study","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Berberine 300 mg three times daily for 14 days versus placebo","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Small short-term study. Probe metabolic ratios are not percentage inhibition of every substrate. No universal dose-adjustment rule; no statistically significant effect is not equivalence.","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":"Healthy human male volunteers; 17 completed","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Drug clearance was measured, rather than inferred from gene expression.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[berberine-p21870106] Repeated administration of berberine inhibits cytochromes P450 in humans. (2012). https://pubmed.ncbi.nlm.nih.gov/21870106/ DOI: 10.1007/s00228-011-1108-2","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Oral probe pharmacokinetics and urinary metabolite ratios","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"556286cf-e733-5689-878b-6d8775cd7c9a","evidence_kind":"source_excerpt","locator":"Lines 662-673","start_line":662,"end_line":673,"excerpt":"### berberine-human-cyp-3a4\nRepeated berberine inhibited CYP3A4 phenotypic activity, with midazolam oral clearance reduced by 27%.\nCondition category: normal\nnutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Drug clearance was measured, rather than inferred from gene expression.\norganism: Healthy human male volunteers; 17 completed\ntissue_or_cell_type: Oral probe pharmacokinetics and urinary metabolite ratios\nexperimental_model: Two-phase randomized crossover enzyme-phenotyping study\nlimitations: Small short-term study. Probe metabolic ratios are not percentage inhibition of every substrate. No universal dose-adjustment rule; no statistically significant effect is not equivalence.\nexposure: Berberine 300 mg three times daily for 14 days versus placebo\nevidence_span: {\"source_cache\": \"artifacts/berberine-research/21870106.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"12e465c3c0a8ce995697a6fb9bf77c079e38b413e82c8b4f2a82e45a3dbf8ae5\", \"start_char\": 0, \"end_char\": 1817, \"text_sha256\": \"12e465c3c0a8ce995697a6fb9bf77c079e38b413e82c8b4f2a82e45a3dbf8ae5\"}\n[berberine-p21870106] Repeated administration of berberine inhibits cytochromes P450 in humans. 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