{"id":"4347feae-bb37-57fb-8f95-80f910003304","stable_key":"7484635e-cc8f-5cd6-a978-6dc5775a7db5:berberine-herg-abundance","predicate":"decreases","statement":"Berberine reduced hERG cell-surface abundance through mechanisms involving caveolin-1 and hERG S6 residues.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"6c38f65a-c262-5011-965c-75c8e9b50257","mechanism_event_label":"Longer exposure can reduce the number of channels as well as block their current.","subject":{"id":"7bbe0633-b2f1-510f-adc0-3c4d0ddad05d","slug":"berberine","display_name":"Berberine","entity_type_key":"small_molecule"},"object":{"id":"d0eb92f4-e8f5-582e-a03b-dde3ab034f5e","slug":"herg-surface-abundance","display_name":"Cell-surface hERG abundance","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"6c38f65a-c262-5011-965c-75c8e9b50257","stable_key":"7484635e-cc8f-5cd6-a978-6dc5775a7db5:berberine-herg-abundance-event","event_type":"biochemical_relationship","label":"Longer exposure can reduce the number of channels as well as block their current.","description":"Berberine reduced hERG cell-surface abundance through mechanisms involving caveolin-1 and hERG S6 residues.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"61c3b97e-dd8a-5f94-a04e-0b6812ce05f9","slug":"kcnh2","display_name":"hERG / KCNH2","entity_type_key":"protein"},"role":"channel","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"bbe0d047-cb2c-57cb-8458-eabae46dde9d","slug":"cav1","display_name":"Human caveolin 1 / CAV1","entity_type_key":"protein"},"role":"regulatory_partner","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":"d0eb92f4-e8f5-582e-a03b-dde3ab034f5e","slug":"herg-surface-abundance","display_name":"Cell-surface hERG abundance","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/26543354.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"56eb3a544eb8700c50931e8bbeb16a24786259d3fb9feebb0b2cbe9e81f02734\", \"start_char\": 0, \"end_char\": 1453, \"text_sha256\": \"56eb3a544eb8700c50931e8bbeb16a24786259d3fb9feebb0b2cbe9e81f02734\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Cell-surface protein regulation and mutagenesis","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Berberine exposure and caveolin-1 knockdown","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Channel abundance and direct current block are distinct mechanisms. Experimental rescue compounds are not clinical antidote recommendations.","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-expressing HEK293 cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Longer exposure can reduce the number of channels as well as block their current.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[berberine-p26543354] Mechanism and pharmacological rescue of berberine-induced hERG channel deficiency. (2015). https://pubmed.ncbi.nlm.nih.gov/26543354/ DOI: 10.2147/dddt.s91561","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"hERG membrane stability","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"ff7a84a7-08cb-5f0b-b468-2210e4366004","evidence_kind":"source_excerpt","locator":"Lines 623-634","start_line":623,"end_line":634,"excerpt":"### berberine-herg-abundance\nBerberine reduced hERG cell-surface abundance through mechanisms involving caveolin-1 and hERG S6 residues.\nCondition category: normal\nnutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Longer exposure can reduce the number of channels as well as block their current.\norganism: Human hERG-expressing HEK293 cells\ntissue_or_cell_type: hERG membrane stability\nexperimental_model: Cell-surface protein regulation and mutagenesis\nlimitations: Channel abundance and direct current block are distinct mechanisms. Experimental rescue compounds are not clinical antidote recommendations.\nexposure: Berberine exposure and caveolin-1 knockdown\nevidence_span: {\"source_cache\": \"artifacts/berberine-research/26543354.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"56eb3a544eb8700c50931e8bbeb16a24786259d3fb9feebb0b2cbe9e81f02734\", \"start_char\": 0, \"end_char\": 1453, \"text_sha256\": \"56eb3a544eb8700c50931e8bbeb16a24786259d3fb9feebb0b2cbe9e81f02734\"}\n[berberine-p26543354] Mechanism and pharmacological rescue of berberine-induced hERG channel deficiency. (2015). https://pubmed.ncbi.nlm.nih.gov/26543354/ DOI: 10.2147/dddt.s91561","model_system":"Cell-surface protein regulation and mutagenesis","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [berberine-p26543354] Mechanism and pharmacological rescue of berberine-induced hERG channel deficiency. (2015). https://pubmed.ncbi.nlm.nih.gov/26543354/ DOI: 10.2147/dddt.s91561","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}