{"id":"31ea7c24-c918-5fcb-97c0-87e48cd3272b","stable_key":"475ea55a-65e9-51c3-a539-738a6a8f683f:mangiferin-direct-ampk-null","predicate":"no_direct_activation_detected","statement":"Mangiferin and tested metabolites were not direct AMPK activators in the HTRF assay.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"227fac65-7382-5544-94e5-a0e0c53d0b0f","mechanism_event_label":"Activation in a cell can occur through upstream machinery.","subject":{"id":"2cfc0bd9-b5cc-58ab-852a-7705f3d8d47f","slug":"mangiferin","display_name":"Mangiferin","entity_type_key":"small_molecule"},"object":{"id":"cec82fda-f730-56aa-b64f-78d827ef30ea","slug":"ampk-htrf-assay-preparation","display_name":"AMPK HTRF assay preparation, subunit and species composition unresolved","entity_type_key":"protein_family"},"evidence_count":1,"mechanism_event":{"id":"227fac65-7382-5544-94e5-a0e0c53d0b0f","stable_key":"475ea55a-65e9-51c3-a539-738a6a8f683f:mangiferin-direct-ampk-null-event","event_type":"biochemical_relationship","label":"Activation in a cell can occur through upstream machinery.","description":"Mangiferin and tested metabolites were not direct AMPK activators in the HTRF assay.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"d0f7f42a-ac45-5144-9ea5-a7586896cc6e","slug":"norathyriol","display_name":"Norathyriol","entity_type_key":"small_molecule"},"role":"tested_metabolite","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"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":1,"notes":""},{"entity":{"id":"cec82fda-f730-56aa-b64f-78d827ef30ea","slug":"ampk-htrf-assay-preparation","display_name":"AMPK HTRF assay preparation, subunit and species composition unresolved","entity_type_key":"protein_family"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/mangiferin-research/29563875.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"d37dba0eedeba51145eddeb7ff144e8f103ec503718283268fe0ae887d6c4125\", \"start_char\": 0, \"end_char\": 1806, \"text_sha256\": \"d37dba0eedeba51145eddeb7ff144e8f103ec503718283268fe0ae887d6c4125\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"KK-Ay mouse liver experiments and mechanistic HepG2 studies","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Norathyriol in sodium-oleate lipid-loading model; micromolar range","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Phosphorylation and expression are scoped to experiments; no established human fatty-liver therapy or direct SIRT1 ligand claim.","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":"object_scope","value_text":"Human cellular AMPK context; purified assay subunit identity requires full reagent review","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Biochemical AMPK assay, exact subunit preparation not assigned here","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Activation in a cell can occur through upstream machinery.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[mangiferin-p29563875] Mangiferin Improves Hepatic Lipid Metabolism Mainly Through Its Metabolite-Norathyriol by Modulating SIRT-1/AMPK/SREBP-1c Signaling. (2018). https://pubmed.ncbi.nlm.nih.gov/29563875/ DOI: 10.3389/fphar.2018.00201","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"HepG2 cells","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"fbd38c53-67d7-5ae9-8e3b-ba5efe9f6357","evidence_kind":"source_excerpt","locator":"Lines 431-443","start_line":431,"end_line":443,"excerpt":"### mangiferin-direct-ampk-null\nMangiferin and tested metabolites were not direct AMPK activators in the HTRF assay.\nCondition category: normal\nnutrient_topic: Mangiferin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Activation in a cell can occur through upstream machinery.\norganism: Biochemical AMPK assay, exact subunit preparation not assigned here\ntissue_or_cell_type: HepG2 cells\nexperimental_model: KK-Ay mouse liver experiments and mechanistic HepG2 studies\nlimitations: Phosphorylation and expression are scoped to experiments; no established human fatty-liver therapy or direct SIRT1 ligand claim.\nexposure: Norathyriol in sodium-oleate lipid-loading model; micromolar range\nobject_scope: Human cellular AMPK context; purified assay subunit identity requires full reagent review\nevidence_span: {\"source_cache\": \"artifacts/mangiferin-research/29563875.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"d37dba0eedeba51145eddeb7ff144e8f103ec503718283268fe0ae887d6c4125\", \"start_char\": 0, \"end_char\": 1806, \"text_sha256\": \"d37dba0eedeba51145eddeb7ff144e8f103ec503718283268fe0ae887d6c4125\"}\n[mangiferin-p29563875] Mangiferin Improves Hepatic Lipid Metabolism Mainly Through Its Metabolite-Norathyriol by Modulating SIRT-1/AMPK/SREBP-1c Signaling. 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