{"id":"41cb624a-ee7b-51fb-91dd-47cb1789f499","stable_key":"475ea55a-65e9-51c3-a539-738a6a8f683f:mangiferin-ho1-loss","predicate":"weakens_protection","statement":"HO-1 inhibition attenuated the protective effect of mangiferin against H2O2 injury.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"6a0378bd-2d9a-57ba-b6c8-38135934ea89","mechanism_event_label":"The response depended in part on available enzyme activity.","subject":{"id":"7f8fea68-1f38-507b-81a6-231357c7196b","slug":"ho1-inhibitor-exposure","display_name":"Experimental HO-1 inhibitor exposure","entity_type_key":"protein_state"},"object":{"id":"dea4b0cf-198e-54d7-abdc-aea1d82a2de9","slug":"human-rpe-h2o2-injury","display_name":"Hydrogen-peroxide injury in human ARPE-19 cells","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"6a0378bd-2d9a-57ba-b6c8-38135934ea89","stable_key":"475ea55a-65e9-51c3-a539-738a6a8f683f:mangiferin-ho1-loss-event","event_type":"biochemical_relationship","label":"The response depended in part on available enzyme activity.","description":"HO-1 inhibition attenuated the protective effect of mangiferin against H2O2 injury.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"26298c7c-5265-5bf5-a435-e0fa98a3ac10","slug":"hmox1","display_name":"Human heme oxygenase 1 / HMOX1","entity_type_key":"protein"},"role":"affected_machinery","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":"intervention","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"7f8fea68-1f38-507b-81a6-231357c7196b","slug":"ho1-inhibitor-exposure","display_name":"Experimental HO-1 inhibitor exposure","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"dea4b0cf-198e-54d7-abdc-aea1d82a2de9","slug":"human-rpe-h2o2-injury","display_name":"Hydrogen-peroxide injury in human ARPE-19 cells","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/mangiferin-research/38586992.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"3568135f9e3471d748a1f42c7ed136800b1cb9d017ebd9aa1522de71b71a72be\", \"start_char\": 0, \"end_char\": 1792, \"text_sha256\": \"3568135f9e3471d748a1f42c7ed136800b1cb9d017ebd9aa1522de71b71a72be\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Hydrogen-peroxide challenge with pharmacological HO-1 inhibition","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Mangiferin before H2O2 exposure","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Cell protection is not demonstrated retinal clinical efficacy; GPx isoforms unresolved and expression is not cofactor sufficiency.","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":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The response depended in part on available enzyme activity.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[mangiferin-p38586992] Activation of Heme Oxygenase-1 by Mangiferin in Human Retinal Pigment Epithelial Cells Contributes to Blocking Oxidative Damage. (2024). https://pubmed.ncbi.nlm.nih.gov/38586992/ DOI: 10.4062/biomolther.2023.175","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"ARPE-19 retinal pigment epithelial cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"ce4c5905-9ced-5ca8-a1f8-db2cb1b483f1","evidence_kind":"source_excerpt","locator":"Lines 653-664","start_line":653,"end_line":664,"excerpt":"### mangiferin-ho1-loss\nHO-1 inhibition attenuated the protective effect of mangiferin against H2O2 injury.\nCondition category: machinery_impairment\nnutrient_topic: Mangiferin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The response depended in part on available enzyme activity.\norganism: Homo sapiens\ntissue_or_cell_type: ARPE-19 retinal pigment epithelial cells\nexperimental_model: Hydrogen-peroxide challenge with pharmacological HO-1 inhibition\nlimitations: Cell protection is not demonstrated retinal clinical efficacy; GPx isoforms unresolved and expression is not cofactor sufficiency.\nexposure: Mangiferin before H2O2 exposure\nevidence_span: {\"source_cache\": \"artifacts/mangiferin-research/38586992.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"3568135f9e3471d748a1f42c7ed136800b1cb9d017ebd9aa1522de71b71a72be\", \"start_char\": 0, \"end_char\": 1792, \"text_sha256\": \"3568135f9e3471d748a1f42c7ed136800b1cb9d017ebd9aa1522de71b71a72be\"}\n[mangiferin-p38586992] Activation of Heme Oxygenase-1 by Mangiferin in Human Retinal Pigment Epithelial Cells Contributes to Blocking Oxidative Damage. 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