{"id":"cd295e2f-a285-53da-9f14-7a2614329a06","stable_key":"7484635e-cc8f-5cd6-a978-6dc5775a7db5:berberine-ldlr-protein","predicate":"increases_expression_of","statement":"Berberine increased LDLR expression through an ERK-dependent, SREBP-independent post-transcriptional mechanism in human hepatoma cells.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"2e11bf0e-4fa1-5d82-a552-d89e6ad012ef","mechanism_event_label":"More LDL receptor can help cells remove LDL from circulation; the mechanism was tested in cells.","subject":{"id":"7bbe0633-b2f1-510f-adc0-3c4d0ddad05d","slug":"berberine","display_name":"Berberine","entity_type_key":"small_molecule"},"object":{"id":"1023010c-54fb-5cc8-9b53-4869c11ddd09","slug":"ldlr","display_name":"Human low-density lipoprotein receptor / LDLR","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"2e11bf0e-4fa1-5d82-a552-d89e6ad012ef","stable_key":"7484635e-cc8f-5cd6-a978-6dc5775a7db5:berberine-ldlr-protein-event","event_type":"biochemical_relationship","label":"More LDL receptor can help cells remove LDL from circulation; the mechanism was tested in cells.","description":"Berberine increased LDLR expression through an ERK-dependent, SREBP-independent post-transcriptional mechanism in human hepatoma cells.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"2944ff54-7d74-5b34-bc0c-c77ac1444717","slug":"erk1-2","display_name":"ERK1/2 proteins, isoform not resolved","entity_type_key":"protein_family"},"role":"required_signaling_family","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"4575e7d3-793f-5602-a8c1-a832fbf49e12","slug":"ldlr-mrna-stability","display_name":"LDLR mRNA stability","entity_type_key":"cellular_process"},"role":"intermediate","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":"1023010c-54fb-5cc8-9b53-4869c11ddd09","slug":"ldlr","display_name":"Human low-density lipoprotein receptor / LDLR","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/berberine-research/15531889.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"ac2a9817f85e5c1f4f520590f1f2cb1ca820cce75b79120852f616f7ce5bea2f\", \"start_char\": 0, \"end_char\": 1032, \"text_sha256\": \"ac2a9817f85e5c1f4f520590f1f2cb1ca820cce75b79120852f616f7ce5bea2f\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human hepatoma mRNA stability/promoter experiments, animal and small clinical arms","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Berberine exposure with ERK-dependence assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Clinical lipid outcomes do not directly prove this molecular route caused the human effect. Cell response was reported independent of SREBP.","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 hepatoma cells for molecular claims","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"More LDL receptor can help cells remove LDL from circulation; the mechanism was tested in cells.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[berberine-p15531889] Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. (2004). https://pubmed.ncbi.nlm.nih.gov/15531889/ DOI: 10.1038/nm1135","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"LDLR post-transcriptional regulation","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"55640b88-89df-5110-ac76-2bd0a06e3f57","evidence_kind":"source_excerpt","locator":"Lines 454-465","start_line":454,"end_line":465,"excerpt":"### berberine-ldlr-protein\nBerberine increased LDLR expression through an ERK-dependent, SREBP-independent post-transcriptional mechanism in human hepatoma cells.\nCondition category: normal\nnutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: More LDL receptor can help cells remove LDL from circulation; the mechanism was tested in cells.\norganism: Human hepatoma cells for molecular claims\ntissue_or_cell_type: LDLR post-transcriptional regulation\nexperimental_model: Human hepatoma mRNA stability/promoter experiments, animal and small clinical arms\nlimitations: Clinical lipid outcomes do not directly prove this molecular route caused the human effect. Cell response was reported independent of SREBP.\nexposure: Berberine exposure with ERK-dependence assays\nevidence_span: {\"source_cache\": \"artifacts/berberine-research/15531889.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"ac2a9817f85e5c1f4f520590f1f2cb1ca820cce75b79120852f616f7ce5bea2f\", \"start_char\": 0, \"end_char\": 1032, \"text_sha256\": \"ac2a9817f85e5c1f4f520590f1f2cb1ca820cce75b79120852f616f7ce5bea2f\"}\n[berberine-p15531889] Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. (2004). https://pubmed.ncbi.nlm.nih.gov/15531889/ DOI: 10.1038/nm1135","model_system":"Human hepatoma mRNA stability/promoter experiments, animal and small clinical arms","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [berberine-p15531889] Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. (2004). https://pubmed.ncbi.nlm.nih.gov/15531889/ DOI: 10.1038/nm1135","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}