{"id":"ff01f87d-d556-52f3-819d-a0fe4ea7ef04","stable_key":"7484635e-cc8f-5cd6-a978-6dc5775a7db5:berberine-herg-block","predicate":"blocks_open_state_of","statement":"Berberine blocked hERG current, with IC50 about 3.1 micromolar in HEK293 cells and 80 micromolar in oocytes.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"21d1f1dd-1102-50b4-be31-084593dc82e6","mechanism_event_label":"A potassium channel needed for cardiac repolarization is a separate safety-related target.","subject":{"id":"7bbe0633-b2f1-510f-adc0-3c4d0ddad05d","slug":"berberine","display_name":"Berberine","entity_type_key":"small_molecule"},"object":{"id":"61c3b97e-dd8a-5f94-a04e-0b6812ce05f9","slug":"kcnh2","display_name":"hERG / KCNH2","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"21d1f1dd-1102-50b4-be31-084593dc82e6","stable_key":"7484635e-cc8f-5cd6-a978-6dc5775a7db5:berberine-herg-block-event","event_type":"biochemical_relationship","label":"A potassium channel needed for cardiac repolarization is a separate safety-related target.","description":"Berberine blocked hERG current, with IC50 about 3.1 micromolar in HEK293 cells and 80 micromolar in oocytes.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"5dd31e52-f51e-51f3-880e-240abcc0ab1d","slug":"potassium-ion","display_name":"Potassium ion","entity_type_key":"ion"},"role":"conducted_ion","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":"61c3b97e-dd8a-5f94-a04e-0b6812ce05f9","slug":"kcnh2","display_name":"hERG / KCNH2","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/16424781.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"45057bbc2da5981b23041d50a91a8e0adacfc150adf66d23daac0402f8ead682\", \"start_char\": 0, \"end_char\": 1322, \"text_sha256\": \"45057bbc2da5981b23041d50a91a8e0adacfc150adf66d23daac0402f8ead682\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Patch clamp and site-directed mutagenesis","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Berberine concentration-response; hERG mutations","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Different expression systems had markedly different IC50 values. Channel inhibition is a hazard mechanism, not an incidence estimate for arrhythmia in supplement users.","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 hERG expressed in HEK293 cells and Xenopus oocytes","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A potassium channel needed for cardiac repolarization is a separate safety-related target.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[berberine-p16424781] Block of HERG channels by berberine: mechanisms of voltage- and state-dependence probed with site-directed mutant channels. (2006). https://pubmed.ncbi.nlm.nih.gov/16424781/ DOI: 10.1097/01.fjc.0000191564.52242.00","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Cardiac potassium-channel model","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"b9e7a2c3-7f99-5ec0-903c-d8759e5986d9","evidence_kind":"source_excerpt","locator":"Lines 610-621","start_line":610,"end_line":621,"excerpt":"### berberine-herg-block\nBerberine blocked hERG current, with IC50 about 3.1 micromolar in HEK293 cells and 80 micromolar in oocytes.\nCondition category: normal\nnutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A potassium channel needed for cardiac repolarization is a separate safety-related target.\norganism: Human hERG expressed in HEK293 cells and Xenopus oocytes\ntissue_or_cell_type: Cardiac potassium-channel model\nexperimental_model: Patch clamp and site-directed mutagenesis\nlimitations: Different expression systems had markedly different IC50 values. Channel inhibition is a hazard mechanism, not an incidence estimate for arrhythmia in supplement users.\nexposure: Berberine concentration-response; hERG mutations\nevidence_span: {\"source_cache\": \"artifacts/berberine-research/16424781.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"45057bbc2da5981b23041d50a91a8e0adacfc150adf66d23daac0402f8ead682\", \"start_char\": 0, \"end_char\": 1322, \"text_sha256\": \"45057bbc2da5981b23041d50a91a8e0adacfc150adf66d23daac0402f8ead682\"}\n[berberine-p16424781] Block of HERG channels by berberine: mechanisms of voltage- and state-dependence probed with site-directed mutant channels. (2006). https://pubmed.ncbi.nlm.nih.gov/16424781/ DOI: 10.1097/01.fjc.0000191564.52242.00","model_system":"Patch clamp and site-directed mutagenesis","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [berberine-p16424781] Block of HERG channels by berberine: mechanisms of voltage- and state-dependence probed with site-directed mutant channels. (2006). https://pubmed.ncbi.nlm.nih.gov/16424781/ DOI: 10.1097/01.fjc.0000191564.52242.00","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. Not publisher full text.","file_path":"","sha256":"2f376a035ae79c93e62e2ea4a8d5385643bf16553f108d12b6a80c89e6d41f4c","revision_id":"2a099429-1c4a-55be-aa2c-0565d08bda80","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}