{"id":"d6bf7cbc-61ef-5154-a23e-b66dbe60bcd0","stable_key":"3d41d18a-e13a-59a0-a081-55bfcdd43e55:ceylon-gsh-cyp","predicate":"attenuates_inhibition","statement":"Added glutathione modestly but significantly reduced the extent of cinnamaldehyde-dependent CYP2A6 inhibition.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"9013b175-6f05-564f-85f1-b10b5d5a9b50","mechanism_event_label":"Glutathione partially buffered this enzyme effect in the assay; supplement protection was not tested.","subject":{"id":"b44c9e27-4bbb-52d3-a022-14cddded5073","slug":"glutathione","display_name":"GSH","entity_type_key":"small_molecule"},"object":{"id":"44b7b150-3615-5d52-9db8-beb212fc31eb","slug":"cyp2a6","display_name":"Human cytochrome P450 2A6 / CYP2A6","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"9013b175-6f05-564f-85f1-b10b5d5a9b50","stable_key":"3d41d18a-e13a-59a0-a081-55bfcdd43e55:ceylon-gsh-cyp-event","event_type":"biochemical_relationship","label":"Glutathione partially buffered this enzyme effect in the assay; supplement protection was not tested.","description":"Added glutathione modestly but significantly reduced the extent of cinnamaldehyde-dependent CYP2A6 inhibition.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"2dc093c6-9373-5b24-a17b-a6b21b5a0432","slug":"trans-cinnamaldehyde","display_name":"trans-Cinnamaldehyde / cinnamal","entity_type_key":"small_molecule"},"role":"inhibitor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"b44c9e27-4bbb-52d3-a022-14cddded5073","slug":"glutathione","display_name":"GSH","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"44b7b150-3615-5d52-9db8-beb212fc31eb","slug":"cyp2a6","display_name":"Human cytochrome P450 2A6 / CYP2A6","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/ceylon-research/26851241.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"c2fb6b18a3ba708f060d53011ea0e198f98fe980930297e714c488a41413b5a2\", \"start_char\": 0, \"end_char\": 1591, \"text_sha256\": \"c2fb6b18a3ba708f060d53011ea0e198f98fe980930297e714c488a41413b5a2\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Recombinant human CYP assays and mechanistic static modeling","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Cinnamaldehyde, NADPH and glutathione; modeled inhibitor concentrations 0.1 and 1 micromolar","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Enzyme inhibition and model predictions are not measured clinical drug interactions. NADPH omission is not dietary niacin deficiency.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"ceylon","display_name":"Ceylon cinnamon / Cinnamomum verum bark preparations","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Human enzyme preparations; computational model","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Glutathione partially buffered this enzyme effect in the assay; supplement protection was not tested.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[ceylon-p26851241] Inactivation of CYP2A6 by the Dietary Phenylpropanoid trans-Cinnamic Aldehyde (Cinnamaldehyde) and Estimation of Interactions with Nicotine and Letrozole. (2016). https://pubmed.ncbi.nlm.nih.gov/26851241/ DOI: 10.1124/dmd.115.067942","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"CYP2A6 reaction system","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"faee8855-2a8d-5ffd-8f17-531961e615a4","evidence_kind":"source_excerpt","locator":"Lines 740-751","start_line":740,"end_line":751,"excerpt":"### ceylon-gsh-cyp\nAdded glutathione modestly but significantly reduced the extent of cinnamaldehyde-dependent CYP2A6 inhibition.\nCondition category: normal\nnutrient_topic: Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Glutathione partially buffered this enzyme effect in the assay; supplement protection was not tested.\norganism: Human enzyme preparations; computational model\ntissue_or_cell_type: CYP2A6 reaction system\nexperimental_model: Recombinant human CYP assays and mechanistic static modeling\nlimitations: Enzyme inhibition and model predictions are not measured clinical drug interactions. NADPH omission is not dietary niacin deficiency.\nexposure: Cinnamaldehyde, NADPH and glutathione; modeled inhibitor concentrations 0.1 and 1 micromolar\nevidence_span: {\"source_cache\": \"artifacts/ceylon-research/26851241.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"c2fb6b18a3ba708f060d53011ea0e198f98fe980930297e714c488a41413b5a2\", \"start_char\": 0, \"end_char\": 1591, \"text_sha256\": \"c2fb6b18a3ba708f060d53011ea0e198f98fe980930297e714c488a41413b5a2\"}\n[ceylon-p26851241] Inactivation of CYP2A6 by the Dietary Phenylpropanoid trans-Cinnamic Aldehyde (Cinnamaldehyde) and Estimation of Interactions with Nicotine and Letrozole. 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