{"id":"84694a16-c594-53b7-8f87-c2c257cd9275","stable_key":"475ea55a-65e9-51c3-a539-738a6a8f683f:mangiferin-pdk4","predicate":"decreases_expression","statement":"After 24 hours, mangiferin reduced PDK4 protein abundance in C2C12 cells.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"99494182-7fcf-59bd-a85e-e71b3cba74b5","mechanism_event_label":"Longer exposure reduced a kinase that restrains PDH.","subject":{"id":"2cfc0bd9-b5cc-58ab-852a-7705f3d8d47f","slug":"mangiferin","display_name":"Mangiferin","entity_type_key":"small_molecule"},"object":{"id":"0ffa0737-a510-534f-a4bc-e8d40639b3b4","slug":"mouse-pdk4","display_name":"Mouse pyruvate dehydrogenase kinase 4 / Pdk4","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"99494182-7fcf-59bd-a85e-e71b3cba74b5","stable_key":"475ea55a-65e9-51c3-a539-738a6a8f683f:mangiferin-pdk4-event","event_type":"biochemical_relationship","label":"Longer exposure reduced a kinase that restrains PDH.","description":"After 24 hours, mangiferin reduced PDK4 protein abundance in C2C12 cells.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"2cfc0bd9-b5cc-58ab-852a-7705f3d8d47f","slug":"mangiferin","display_name":"Mangiferin","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"0ffa0737-a510-534f-a4bc-e8d40639b3b4","slug":"mouse-pdk4","display_name":"Mouse pyruvate dehydrogenase kinase 4 / Pdk4","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/mangiferin-research/24848064.fulltext.txt\", \"locator\": \"Primary full-text span; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"8cbbc4a9b075ae11f5b88a9929a65c77e6b39870068e320a281bd1802384fec8\", \"start_char\": 30977, \"end_char\": 31862, \"text_sha256\": \"8e9b4448f5213862fa4c8b78f1d49c9f6b4e6faffb97d818dabbd4117d386dba\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"High-fat-fed mice and differentiated C2C12 myotube experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"200 or 1000 micromolar mangiferin, 24 hours; Figure 6","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Cell exposure well above the parent plasma concentrations reported in the selected human PK study; reduced expression is not direct kinase-binding evidence.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Mangiferin research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"mangiferin","display_name":"Mangiferin","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Mus musculus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Longer exposure reduced a kinase that restrains PDH.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[mangiferin-p24848064] Mangiferin stimulates carbohydrate oxidation and protects against metabolic disorders induced by high-fat diets. (2014). https://pubmed.ncbi.nlm.nih.gov/24848064/ DOI: 10.2337/db14-0006","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Skeletal muscle and cultured myotubes","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"8fd97e0a-50c8-58e8-bf6a-866f4fd529cd","evidence_kind":"source_excerpt","locator":"Lines 353-364","start_line":353,"end_line":364,"excerpt":"### mangiferin-pdk4\nAfter 24 hours, mangiferin reduced PDK4 protein abundance in C2C12 cells.\nCondition category: normal\nnutrient_topic: Mangiferin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Longer exposure reduced a kinase that restrains PDH.\norganism: Mus musculus\ntissue_or_cell_type: Skeletal muscle and cultured myotubes\nexperimental_model: High-fat-fed mice and differentiated C2C12 myotube experiments\nlimitations: Cell exposure well above the parent plasma concentrations reported in the selected human PK study; reduced expression is not direct kinase-binding evidence.\nexposure: 200 or 1000 micromolar mangiferin, 24 hours; Figure 6\nevidence_span: {\"source_cache\": \"artifacts/mangiferin-research/24848064.fulltext.txt\", \"locator\": \"Primary full-text span; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"8cbbc4a9b075ae11f5b88a9929a65c77e6b39870068e320a281bd1802384fec8\", \"start_char\": 30977, \"end_char\": 31862, \"text_sha256\": \"8e9b4448f5213862fa4c8b78f1d49c9f6b4e6faffb97d818dabbd4117d386dba\"}\n[mangiferin-p24848064] Mangiferin stimulates carbohydrate oxidation and protects against metabolic disorders induced by high-fat diets. (2014). https://pubmed.ncbi.nlm.nih.gov/24848064/ DOI: 10.2337/db14-0006","model_system":"High-fat-fed mice and differentiated C2C12 myotube experiments","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [mangiferin-p24848064] Mangiferin stimulates carbohydrate oxidation and protects against metabolic disorders induced by high-fat diets. (2014). https://pubmed.ncbi.nlm.nih.gov/24848064/ DOI: 10.2337/db14-0006","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"267f942a-695a-5b62-a858-f71c06321ff5","stable_key":"import-475ea55a-65e9-51c3-a539-738a6a8f683f","title":"Mangiferin: metabolism, signaling and nutrient connections (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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