{"id":"145da47e-b362-5352-bbd3-d6b6c905436c","stable_key":"7484635e-cc8f-5cd6-a978-6dc5775a7db5:berberine-chloride-secretion","predicate":"decreases","statement":"Berberine decreased forskolin-stimulated chloride secretion in T84 monolayers through a predominantly PKC-alpha-dependent pathway.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"4a0a1f3e-b9cb-5984-a86d-d66634e2884f","mechanism_event_label":"The potassium-channel response is connected to movement of a different ion: chloride.","subject":{"id":"7bbe0633-b2f1-510f-adc0-3c4d0ddad05d","slug":"berberine","display_name":"Berberine","entity_type_key":"small_molecule"},"object":{"id":"3d908f8f-f213-5a56-9cf3-0c239d51daaf","slug":"colonic-chloride-secretion","display_name":"Colonic epithelial chloride secretion","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"4a0a1f3e-b9cb-5984-a86d-d66634e2884f","stable_key":"7484635e-cc8f-5cd6-a978-6dc5775a7db5:berberine-chloride-secretion-event","event_type":"biochemical_relationship","label":"The potassium-channel response is connected to movement of a different ion: chloride.","description":"Berberine decreased forskolin-stimulated chloride secretion in T84 monolayers through a predominantly PKC-alpha-dependent pathway.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"d4c19e4b-d83b-5cda-8c7d-041d7fe6ada0","slug":"prkca","display_name":"Protein kinase C alpha (PRKCA)","entity_type_key":"protein"},"role":"signaling_partner","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"6f35aa38-f875-5759-b749-97a2f6480ff3","slug":"chloride-ion","display_name":"Chloride ion","entity_type_key":"ion"},"role":"transported_ion","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"7621dbe0-e1dc-5d55-b206-56820074c8ac","slug":"kcnq1","display_name":"Human KCNQ1 / Kv7.1 potassium channel","entity_type_key":"protein"},"role":"channel_context","stoichiometry":null,"state_label":"","sequence_order":2,"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":3,"notes":""},{"entity":{"id":"3d908f8f-f213-5a56-9cf3-0c239d51daaf","slug":"colonic-chloride-secretion","display_name":"Colonic epithelial chloride secretion","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/berberine-research/21747769.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"b8864a2844ea828aeabcfc05219050ac1cb6efe7f24c663dc3302887f7f59ad4\", \"start_char\": 0, \"end_char\": 1734, \"text_sha256\": \"b8864a2844ea828aeabcfc05219050ac1cb6efe7f24c663dc3302887f7f59ad4\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Ussing-chamber short-circuit current, patch clamp and kinase perturbation","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Forskolin-stimulated secretion and berberine; IC50 about 80 micromolar","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Intestinal cell mechanism, not proof of systemic potassium depletion. The observed channel complex differs from cardiac KCNQ1/KCNE1.","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 T84 colonic cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The potassium-channel response is connected to movement of a different ion: chloride.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[berberine-p21747769] Berberine Reduces cAMP-Induced Chloride Secretion in T84 Human Colonic Carcinoma Cells through Inhibition of Basolateral KCNQ1 Channels. (2011). https://pubmed.ncbi.nlm.nih.gov/21747769/ DOI: 10.3389/fphys.2011.00033","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Basolateral potassium recycling and chloride secretion","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"5f8d021b-9218-5857-86b6-02f6bccb3673","evidence_kind":"source_excerpt","locator":"Lines 571-582","start_line":571,"end_line":582,"excerpt":"### berberine-chloride-secretion\nBerberine decreased forskolin-stimulated chloride secretion in T84 monolayers through a predominantly PKC-alpha-dependent pathway.\nCondition category: normal\nnutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The potassium-channel response is connected to movement of a different ion: chloride.\norganism: Human T84 colonic cells\ntissue_or_cell_type: Basolateral potassium recycling and chloride secretion\nexperimental_model: Ussing-chamber short-circuit current, patch clamp and kinase perturbation\nlimitations: Intestinal cell mechanism, not proof of systemic potassium depletion. The observed channel complex differs from cardiac KCNQ1/KCNE1.\nexposure: Forskolin-stimulated secretion and berberine; IC50 about 80 micromolar\nevidence_span: {\"source_cache\": \"artifacts/berberine-research/21747769.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"b8864a2844ea828aeabcfc05219050ac1cb6efe7f24c663dc3302887f7f59ad4\", \"start_char\": 0, \"end_char\": 1734, \"text_sha256\": \"b8864a2844ea828aeabcfc05219050ac1cb6efe7f24c663dc3302887f7f59ad4\"}\n[berberine-p21747769] Berberine Reduces cAMP-Induced Chloride Secretion in T84 Human Colonic Carcinoma Cells through Inhibition of Basolateral KCNQ1 Channels. (2011). https://pubmed.ncbi.nlm.nih.gov/21747769/ DOI: 10.3389/fphys.2011.00033","model_system":"Ussing-chamber short-circuit current, patch clamp and kinase perturbation","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [berberine-p21747769] Berberine Reduces cAMP-Induced Chloride Secretion in T84 Human Colonic Carcinoma Cells through Inhibition of Basolateral KCNQ1 Channels. (2011). https://pubmed.ncbi.nlm.nih.gov/21747769/ DOI: 10.3389/fphys.2011.00033","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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