{"id":"0832e021-4162-5ed0-8548-c992dcafef84","stable_key":"7484635e-cc8f-5cd6-a978-6dc5775a7db5:berberine-glycolytic-lactate","predicate":"increases","statement":"Berberine increased lactate release in HepG2 and C2C12 cells, including during AMPK-pathway blockade.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"e3cb6b48-9c5b-56ee-98af-1c842f9838c5","mechanism_event_label":"More glycolytic use of glucose can increase lactate production; this is not a clinical lactic-acidosis incidence estimate.","subject":{"id":"7bbe0633-b2f1-510f-adc0-3c4d0ddad05d","slug":"berberine","display_name":"Berberine","entity_type_key":"small_molecule"},"object":{"id":"4f4a7ecb-41d2-5520-89af-8d520abf6db3","slug":"cellular-lactate-release","display_name":"Cellular lactate release","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"e3cb6b48-9c5b-56ee-98af-1c842f9838c5","stable_key":"7484635e-cc8f-5cd6-a978-6dc5775a7db5:berberine-glycolytic-lactate-event","event_type":"biochemical_relationship","label":"More glycolytic use of glucose can increase lactate production; this is not a clinical lactic-acidosis incidence estimate.","description":"Berberine increased lactate release in HepG2 and C2C12 cells, including during AMPK-pathway blockade.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"8ae7848b-f172-5e09-8acf-5ca914907b0b","slug":"glucose","display_name":"D-glucose","entity_type_key":"small_molecule"},"role":"substrate_context","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"5ebd9a7c-b151-5b70-b70d-7d33067d4ebf","slug":"lactate","display_name":"L-Lactate","entity_type_key":"small_molecule"},"role":"product","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":"4f4a7ecb-41d2-5520-89af-8d520abf6db3","slug":"cellular-lactate-release","display_name":"Cellular lactate release","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/25072399.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"aa8c67580ab0a69c335873a80e94bbe418ac93b88bcad42c72e1eeb564ff828a\", \"start_char\": 0, \"end_char\": 1385, \"text_sha256\": \"aa8c67580ab0a69c335873a80e94bbe418ac93b88bcad42c72e1eeb564ff828a\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Pharmacological inhibition, siRNA and dominant-negative AMPK experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Berberine concentration-response; 20 micromolar in phosphorylation experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"AMPK is not necessary for every glucose response. This does not show that all other berberine actions are AMPK-independent; cell concentrations may exceed circulating parent drug.","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 HepG2 hepatocytes and mouse C2C12 myotubes","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"More glycolytic use of glucose can increase lactate production; this is not a clinical lactic-acidosis incidence estimate.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[berberine-p25072399] Berberine promotes glucose consumption independently of AMP-activated protein kinase activation. (2014). https://pubmed.ncbi.nlm.nih.gov/25072399/ DOI: 10.1371/journal.pone.0103702","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Glucose consumption, lactate release and mitochondrial respiration","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"322e086c-e9ba-5da0-b54b-809c73a79f4d","evidence_kind":"source_excerpt","locator":"Lines 363-374","start_line":363,"end_line":374,"excerpt":"### berberine-glycolytic-lactate\nBerberine increased lactate release in HepG2 and C2C12 cells, including during AMPK-pathway blockade.\nCondition category: normal\nnutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: More glycolytic use of glucose can increase lactate production; this is not a clinical lactic-acidosis incidence estimate.\norganism: Human HepG2 hepatocytes and mouse C2C12 myotubes\ntissue_or_cell_type: Glucose consumption, lactate release and mitochondrial respiration\nexperimental_model: Pharmacological inhibition, siRNA and dominant-negative AMPK experiments\nlimitations: AMPK is not necessary for every glucose response. This does not show that all other berberine actions are AMPK-independent; cell concentrations may exceed circulating parent drug.\nexposure: Berberine concentration-response; 20 micromolar in phosphorylation experiments\nevidence_span: {\"source_cache\": \"artifacts/berberine-research/25072399.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"aa8c67580ab0a69c335873a80e94bbe418ac93b88bcad42c72e1eeb564ff828a\", \"start_char\": 0, \"end_char\": 1385, \"text_sha256\": \"aa8c67580ab0a69c335873a80e94bbe418ac93b88bcad42c72e1eeb564ff828a\"}\n[berberine-p25072399] Berberine promotes glucose consumption independently of AMP-activated protein kinase activation. (2014). https://pubmed.ncbi.nlm.nih.gov/25072399/ DOI: 10.1371/journal.pone.0103702","model_system":"Pharmacological inhibition, siRNA and dominant-negative AMPK experiments","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [berberine-p25072399] Berberine promotes glucose consumption independently of AMP-activated protein kinase activation. (2014). https://pubmed.ncbi.nlm.nih.gov/25072399/ DOI: 10.1371/journal.pone.0103702","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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