{"id":"b5bccba7-42c6-58cc-8dcf-80e4b9ebf12c","stable_key":"7484635e-cc8f-5cd6-a978-6dc5775a7db5:berberine-hnf1a-degradation:signed","predicate":"accelerates_proteasomal_degradation_of","statement":"Berberine accelerated ubiquitin-associated proteasomal degradation of HNF1A protein in HepG2 cells.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"c3bcf238-1892-5ce5-90da-dea79336934d","mechanism_event_label":"The cell made less of a cholesterol-regulating signal because its upstream regulator was degraded.","subject":{"id":"7bbe0633-b2f1-510f-adc0-3c4d0ddad05d","slug":"berberine","display_name":"Berberine","entity_type_key":"small_molecule"},"object":{"id":"c9b0f8e4-4823-5067-a352-61b4c37cd11b","slug":"hnf1a","display_name":"Human hepatocyte nuclear factor 1 alpha / HNF1A","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"c3bcf238-1892-5ce5-90da-dea79336934d","stable_key":"7484635e-cc8f-5cd6-a978-6dc5775a7db5:berberine-hnf1a-degradation-event","event_type":"biochemical_relationship","label":"The cell made less of a cholesterol-regulating signal because its upstream regulator was degraded.","description":"Berberine accelerated ubiquitin-associated proteasomal degradation of HNF1A protein in HepG2 cells.","status":"provisional","compartment":null,"participants":[{"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":0,"notes":""},{"entity":{"id":"c9b0f8e4-4823-5067-a352-61b4c37cd11b","slug":"hnf1a","display_name":"Human hepatocyte nuclear factor 1 alpha / HNF1A","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/berberine-research/25540198.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"08c835c28631cd0c79be4e5a602216f8eddcd0f2d0c967074d7c9faf4aa9e446\", \"start_char\": 0, \"end_char\": 1769, \"text_sha256\": \"08c835c28631cd0c79be4e5a602216f8eddcd0f2d0c967074d7c9faf4aa9e446\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Protein-turnover and proteasome-inhibitor experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Berberine, ubiquitin assays and proteasome inhibition","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"HNF1A protein turnover differs from HNF1A gene transcription. 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Proteasome inhibitors are experimental probes, not suggested combination treatment.\nexposure: Berberine, ubiquitin assays and proteasome inhibition\nevidence_span: {\"source_cache\": \"artifacts/berberine-research/25540198.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"08c835c28631cd0c79be4e5a602216f8eddcd0f2d0c967074d7c9faf4aa9e446\", \"start_char\": 0, \"end_char\": 1769, \"text_sha256\": \"08c835c28631cd0c79be4e5a602216f8eddcd0f2d0c967074d7c9faf4aa9e446\"}\n[berberine-p25540198] Inhibition of PCSK9 transcription by berberine involves down-regulation of hepatic HNF1α protein expression through the ubiquitin-proteasome degradation pathway. 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The recorded limitation that HNF1A protein turnover differs from HNF1A gene transcription is carried over unchanged.","source_claim_id":"b5bccba7-42c6-58cc-8dcf-80e4b9ebf12c","source_claim_key":"7484635e-cc8f-5cd6-a978-6dc5775a7db5:berberine-hnf1a-degradation:signed","source_statement":"Berberine accelerated ubiquitin-associated proteasomal degradation of HNF1A protein in HepG2 cells.","target_claim_id":"506590cd-685c-5a55-adf5-54a59da0e591","target_claim_key":"7484635e-cc8f-5cd6-a978-6dc5775a7db5:berberine-hnf1a-degradation","target_statement":"Berberine accelerated ubiquitin-associated proteasomal degradation of HNF1A protein in HepG2 cells."}],"conflicts":[],"corrections":[{"id":"b8197283-8e25-5da2-9843-c48caa866df5","title":"7484635e-cc8f-5cd6-a978-6dc5775a7db5:berberine-hnf1a-degradation:signed / 7484635e-cc8f-5cd6-a978-6dc5775a7db5:berberine-hnf1a-degradation","kind":"supersedes","status":"corrected","why":"The ledger explicitly records that ‘Berberine accelerated ubiquitin-associated proteasomal degradation of HNF1A protein in HepG2 cells.’ supersedes ‘Berberine accelerated ubiquitin-associated proteasomal degradation of HNF1A protein in HepG2 cells.’. Direction was left unset while the record stated it twice: the predicate accelerates_proteasomal_degradation_of and the statement 'Berberine accelerated ubiquitin-associated proteasomal degradation of HNF1A protein in HepG2 cells.' Accelerated degradation of a protein lowers that protein, so the replacement carries direction negative on HNF1A protein. No text rule can read this: the direction lives in the word degradation, and a rule reading that word would invert the negations and the protease-side claims elsewhere in this ledger. The recorded limitation that HNF1A protein turnover differs from HNF1A gene transcription is carried over unchanged.","resolution":"The earlier statement is superseded; both versions are retained in correction history.","created_at":"2026-10-02 02:42:45","record_type":"correction","display_label":"Correction history","record_url":"/corrections/b8197283-8e25-5da2-9843-c48caa866df5","sides":[{"conflict_id":"b8197283-8e25-5da2-9843-c48caa866df5","ordinal":0,"label":"Related statement","revision_id":"2a099429-1c4a-55be-aa2c-0565d08bda80","start_line":467,"end_line":478,"quote":"### berberine-hnf1a-degradation\nBerberine accelerated ubiquitin-associated proteasomal degradation of HNF1A protein in HepG2 cells.\nCondition category: normal\nnutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The cell made less of a cholesterol-regulating signal because its upstream regulator was degraded.\norganism: Human HepG2 cells; separate mouse and hamster arms\ntissue_or_cell_type: HNF1A and PCSK9 gene regulation\nexperimental_model: Protein-turnover and proteasome-inhibitor experiments\nlimitations: HNF1A protein turnover differs from HNF1A gene transcription. Proteasome inhibitors are experimental probes, not suggested combination treatment.\nexposure: Berberine, ubiquitin assays and proteasome inhibition\nevidence_span: {\"source_cache\": \"artifacts/berberine-research/25540198.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"08c835c28631cd0c79be4e5a602216f8eddcd0f2d0c967074d7c9faf4aa9e446\", \"start_char\": 0, \"end_char\": 1769, \"text_sha256\": \"08c835c28631cd0c79be4e5a602216f8eddcd0f2d0c967074d7c9faf4aa9e446\"}\n[berberine-p25540198] Inhibition of PCSK9 transcription by berberine involves down-regulation of hepatic HNF1α protein expression through the ubiquitin-proteasome degradation pathway. (2015). https://pubmed.ncbi.nlm.nih.gov/25540198/ DOI: 10.1074/jbc.m114.597229","source_key":"import-7484635e-cc8f-5cd6-a978-6dc5775a7db5","source_title":"Berberine: metabolism, nutrient connections and drug interactions (2026-09-17)","claim_ids":["b5bccba7-42c6-58cc-8dcf-80e4b9ebf12c"]},{"conflict_id":"b8197283-8e25-5da2-9843-c48caa866df5","ordinal":1,"label":"Opposing statement","revision_id":"2a099429-1c4a-55be-aa2c-0565d08bda80","start_line":467,"end_line":478,"quote":"### berberine-hnf1a-degradation\nBerberine accelerated ubiquitin-associated proteasomal degradation of HNF1A protein in HepG2 cells.\nCondition category: normal\nnutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The cell made less of a cholesterol-regulating signal because its upstream regulator was degraded.\norganism: Human HepG2 cells; separate mouse and hamster arms\ntissue_or_cell_type: HNF1A and PCSK9 gene regulation\nexperimental_model: Protein-turnover and proteasome-inhibitor experiments\nlimitations: HNF1A protein turnover differs from HNF1A gene transcription. Proteasome inhibitors are experimental probes, not suggested combination treatment.\nexposure: Berberine, ubiquitin assays and proteasome inhibition\nevidence_span: {\"source_cache\": \"artifacts/berberine-research/25540198.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"08c835c28631cd0c79be4e5a602216f8eddcd0f2d0c967074d7c9faf4aa9e446\", \"start_char\": 0, \"end_char\": 1769, \"text_sha256\": \"08c835c28631cd0c79be4e5a602216f8eddcd0f2d0c967074d7c9faf4aa9e446\"}\n[berberine-p25540198] Inhibition of PCSK9 transcription by berberine involves down-regulation of hepatic HNF1α protein expression through the ubiquitin-proteasome degradation pathway. (2015). https://pubmed.ncbi.nlm.nih.gov/25540198/ DOI: 10.1074/jbc.m114.597229","source_key":"import-7484635e-cc8f-5cd6-a978-6dc5775a7db5","source_title":"Berberine: metabolism, nutrient connections and drug interactions (2026-09-17)","claim_ids":["506590cd-685c-5a55-adf5-54a59da0e591"]}]}],"research":null}