{"id":"2f937fb5-fe6c-560c-b948-b3d70dea5602","stable_key":"788beb7b-7928-5f89-83d4-5556abf3702c:fulvic-acid-p65-binding","predicate":"reduces_promoter_occupancy","statement":"Fulvic pretreatment reduced p65 binding at the COX-2 promoter in stimulated U937 cells.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"dee29fea-db9b-5833-9d80-aefad8cda181","mechanism_event_label":"The inflammatory transcription factor occupied the promoter less.","subject":{"id":"8e814f0b-25bf-52c1-84b8-b1c12bbb6547","slug":"esther-fulvic-2015","display_name":"Esther Material Technology fulvic preparation, 2015 study","entity_type_key":"chemical_species"},"object":{"id":"ecf9653e-8710-540d-953a-78ef96bf4752","slug":"rela","display_name":"Human NF-kappa-B p65 / RELA","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"dee29fea-db9b-5833-9d80-aefad8cda181","stable_key":"788beb7b-7928-5f89-83d4-5556abf3702c:fulvic-acid-p65-binding-event","event_type":"observed_relationship","label":"The inflammatory transcription factor occupied the promoter less.","description":"Fulvic pretreatment reduced p65 binding at the COX-2 promoter in stimulated U937 cells.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"8e814f0b-25bf-52c1-84b8-b1c12bbb6547","slug":"esther-fulvic-2015","display_name":"Esther Material Technology fulvic preparation, 2015 study","entity_type_key":"chemical_species"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"ecf9653e-8710-540d-953a-78ef96bf4752","slug":"rela","display_name":"Human NF-kappa-B p65 / RELA","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"0aa6c0fc-8374-56e0-b172-6c40b6366d21","slug":"fulvic-acid","display_name":"Fulvic acid (heterogeneous humic fraction)","entity_type_key":"chemical_species"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"5b635b42-bc0d-5c54-aa94-9cf76cd0ed47","slug":"homocysteine","display_name":"Homocysteine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"c8a31ed4-f2ca-5d43-8352-e9935129a785","slug":"ptgs2","display_name":"Cyclooxygenase-2 (PTGS2)","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human primary monocytes and U937 cells; Esther 20% stock diluted to 0.5-10 micrograms/mL, 4-hour pretreatment; homocysteine stimulation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Cell exposure does not establish oral exposure, homocysteine removal or cardiovascular benefit. Results text reports homocysteine 200 micromolar, while figure captions say 200 micrograms/mL; dose units are unresolved. Inhibitor concentrations also need original-record clarification. ChIP is a cultured-cell result; the paper uses in vivo to mean within cells.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"fulvic-acid","display_name":"Fulvic acid (heterogeneous humic fraction)","entity_type_key":"chemical_species"}},{"dimension":"plain_language","value_text":"The inflammatory transcription factor occupied the promoter less.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Fulvic acid attenuates homocysteine-induced cyclooxygenase-2 expression in human monocytes. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25888188/ · DOI 10.1186/s12906-015-0583-x","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"c9e51711-6ef0-55c3-884e-5d5bbba3633e","evidence_kind":"source_excerpt","locator":"Lines 52-58","start_line":52,"end_line":58,"excerpt":"## fulvic-acid-p65-binding\nThe inflammatory transcription factor occupied the promoter less.\nFulvic pretreatment reduced p65 binding at the COX-2 promoter in stimulated U937 cells.\nModel: Human primary monocytes and U937 cells; Esther 20% stock diluted to 0.5-10 micrograms/mL, 4-hour pretreatment; homocysteine stimulation.\nLimitations: Cell exposure does not establish oral exposure, homocysteine removal or cardiovascular benefit. Results text reports homocysteine 200 micromolar, while figure captions say 200 micrograms/mL; dose units are unresolved. Inhibitor concentrations also need original-record clarification. ChIP is a cultured-cell result; the paper uses in vivo to mean within cells.\nEvidence access: Primary full text\nFulvic acid attenuates homocysteine-induced cyclooxygenase-2 expression in human monocytes. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25888188/ · DOI 10.1186/s12906-015-0583-x","model_system":"Human primary monocytes and U937 cells; Esther 20% stock diluted to 0.5-10 micrograms/mL, 4-hour pretreatment; homocysteine stimulation.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"b00a1818-46e4-52cc-8dfe-a647d5c08ed7","stable_key":"import-788beb7b-7928-5f89-83d4-5556abf3702c","title":"Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text.","file_path":"","sha256":"52c2c3ee6bb23d943a40e1c39dd9de5cca7acd6efa72479cb824149e85cc7968","revision_id":"94dfc01b-c93e-55ff-8f48-bb2e9a1979f6","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}