{"id":"460fe03a-05b3-5727-ae08-9b5af7634021","stable_key":"35ec55a7-323c-5c28-979e-3bdafe9d5769:hcaec-vcam","predicate":"decreases_in_recorded_experiment","statement":"Reconstructed C3G metabolite mixtures lowered TNF-stimulated VCAM-1 release in HCAEC under the tested conditions.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"1d4f72f0-13a5-52dd-bb83-ac5aa9a54664","mechanism_event_label":"Reconstructed C3G metabolite mixtures lowered TNF-stimulated VCAM-1 release in HCAEC under the tested conditions.","subject":{"id":"415608c3-d57b-5b17-aa69-c19e547330b9","slug":"c3g-human-serum-metabolite-signatures","display_name":"Reconstructed 1-, 6- and 24-hour human C3G metabolite signatures","entity_type_key":"chemical_species"},"object":{"id":"281d02c8-2752-55f3-938d-4c4d313cdf8c","slug":"human-hcaec-vcam1-release","display_name":"Soluble VCAM-1 release by human coronary-artery endothelial cells","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"1d4f72f0-13a5-52dd-bb83-ac5aa9a54664","stable_key":"35ec55a7-323c-5c28-979e-3bdafe9d5769:hcaec-vcam-event","event_type":"experimental_observation","label":"Reconstructed C3G metabolite mixtures lowered TNF-stimulated VCAM-1 release in HCAEC under the tested conditions.","description":"**Low-concentration mixtures can change VCAM-1 without a universal IL-6 effect.** Warner's 2017 study reconstructed the tracer cohort's 1-, 6- and 24-hour serum signatures. Mixtures reduced TNF-stimulated VCAM-1; some effects remained at total concentrations of 0.19–0.44 µM. IL-6 secretion decreased in HUVECs at selected higher mixture concentrations, but not detectably in HCAECs. TNF stimulation also differed between the cell types. Figure 3 preserves this important cell-specific null. Phosphorylated NF-κB p65 did not significantly change in the tested HCAEC experiment. These are mixture findings, not proof that PCA alone suppresses NF-κB at dietary exposure. [Warner et al., 2017, Figures 2–5](https://pmc.ncbi.nlm.nih.gov/articles/PMC5600085/).","status":"provisional","compartment":null,"participants":[{"entity":{"id":"415608c3-d57b-5b17-aa69-c19e547330b9","slug":"c3g-human-serum-metabolite-signatures","display_name":"Reconstructed 1-, 6- and 24-hour human C3G metabolite signatures","entity_type_key":"chemical_species"},"role":"tested factor","stoichiometry":null,"state_label":"C3G serum-signature mixture plus TNF","sequence_order":0,"notes":""},{"entity":{"id":"281d02c8-2752-55f3-938d-4c4d313cdf8c","slug":"human-hcaec-vcam1-release","display_name":"Soluble VCAM-1 release by human coronary-artery endothelial cells","entity_type_key":"cellular_process"},"role":"measured outcome","stoichiometry":null,"state_label":"decrease","sequence_order":1,"notes":""},{"entity":{"id":"d039b9f8-ea24-586a-a617-4d625e185d7d","slug":"human-vcam1","display_name":"Human vascular cell adhesion molecule 1 / VCAM1","entity_type_key":"protein"},"role":"released protein","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"600d5b09-e092-5146-af1e-2510cf17bac6","slug":"tnf","display_name":"Tumor necrosis factor","entity_type_key":"cytokine"},"role":"joint inflammatory challenge","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Full text retrieved; relevant methods/results/figure text reviewed. No independent raw-data verification.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_condition","value_text":"added","comparator":"TNF plus vehicle","unit":null,"notes":"Condition belongs to the full experimental contrast; do not separate a joint intervention.","entity":{"slug":"c3g-human-serum-metabolite-signatures","display_name":"Reconstructed 1-, 6- and 24-hour human C3G metabolite signatures","entity_type_key":"chemical_species"}},{"dimension":"experimental_condition","value_text":"present","comparator":"TNF plus vehicle","unit":null,"notes":"Condition belongs to the full experimental contrast; do not separate a joint intervention.","entity":{"slug":"tnf","display_name":"Tumor necrosis factor","entity_type_key":"cytokine"}},{"dimension":"experimental_contrast","value_text":"{\"intervention\": \"C3G serum-signature mixture plus TNF\", \"comparator\": \"TNF plus vehicle\", \"endpoint\": \"Reconstructed C3G metabolite mixtures lowered TNF-stimulated VCAM-1 release in HCAEC under the tested conditions.\", \"effect_direction\": \"decrease\", \"combination\": \"joint\", \"conditions\": [{\"entity_slug\": \"c3g-human-serum-metabolite-signatures\", \"state\": \"added\"}, {\"entity_slug\": \"tnf\", \"state\": \"present\"}]}","comparator":null,"unit":null,"notes":"Explicit extracted experimental comparison; source-derived draft.","entity":null},{"dimension":"experimental_model","value_text":"HCAEC culture; 1/6/24-hour serum signatures; 0.1x/1x/10x observed mean concentrations; 24-hour cytokine stimulation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"interpretation_status","value_text":"Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Some VCAM effects survived 0.19-0.44 uM total mixture; not every endpoint or every concentration. Mixture does not identify one active component.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Reconstructed C3G metabolite mixtures lowered TNF-stimulated VCAM-1 release in HCAEC under the tested conditions.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Signatures of anthocyanin metabolites identified in humans inhibit biomarkers of vascular inflammation in human endothelial cells. | 2017 | DOI 10.1002/mnfr.201700053 | PMID 28457017 | https://pubmed.ncbi.nlm.nih.gov/28457017/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC5600085/ | https://doi.org/10.1002/mnfr.201700053","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"source_locator","value_text":"Reviewed reference lines 58-58; exact primary location described in quoted passage where extracted.","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"884c5625-d840-5f79-bddb-4c63971b467d","evidence_kind":"source_excerpt","locator":"Lines 58-58","start_line":58,"end_line":58,"excerpt":"**Low-concentration mixtures can change VCAM-1 without a universal IL-6 effect.** Warner's 2017 study reconstructed the tracer cohort's 1-, 6- and 24-hour serum signatures. Mixtures reduced TNF-stimulated VCAM-1; some effects remained at total concentrations of 0.19–0.44 µM. IL-6 secretion decreased in HUVECs at selected higher mixture concentrations, but not detectably in HCAECs. TNF stimulation also differed between the cell types. Figure 3 preserves this important cell-specific null. Phosphorylated NF-κB p65 did not significantly change in the tested HCAEC experiment. These are mixture findings, not proof that PCA alone suppresses NF-κB at dietary exposure. [Warner et al., 2017, Figures 2–5](https://pmc.ncbi.nlm.nih.gov/articles/PMC5600085/).","model_system":"HCAEC culture; 1/6/24-hour serum signatures; 0.1x/1x/10x observed mean concentrations; 24-hour cytokine stimulation.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Exact excerpt of the retained AI-assisted reviewed reference; primary sources are cited in primary_references and access scope is retained. Not a verbatim quotation from a primary paper.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"b08e7f7d-4d34-56d7-a185-2124f8d72b3c","stable_key":"import-35ec55a7-323c-5c28-979e-3bdafe9d5769","title":"Anthocyanins: detailed mechanisms of action (reviewed 4 October 2026)","document_type":"imported_text","citation_label":"Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication.","file_path":"","sha256":"7cff1a47fbd9c625412b84162b1c823004b4162b7c009f9a11d5807fb8e04ef9","revision_id":"1bd4fa42-bfeb-5148-8250-fc363d8c1de0","review_status":"unverified_draft","notes":""}}],"relations":[{"id":"d9fb5969-d1b7-5b44-972f-d5a027445a5e","relation_type":"limits_scope_of","notes":"VCAM-1 reduction did not demonstrate phospho-p65 suppression in the measured assay.","source_claim_id":"3648693d-5a8d-5f7b-b149-ef2d24ac2d4e","source_claim_key":"35ec55a7-323c-5c28-979e-3bdafe9d5769:p65-null","source_statement":"The tested metabolite signatures did not significantly change phosphorylated NF-kappa-B p65 in stimulated HCAECs.","target_claim_id":"460fe03a-05b3-5727-ae08-9b5af7634021","target_claim_key":"35ec55a7-323c-5c28-979e-3bdafe9d5769:hcaec-vcam","target_statement":"Reconstructed C3G metabolite mixtures lowered TNF-stimulated VCAM-1 release in HCAEC under the tested conditions."}],"conflicts":[],"corrections":[],"research":null}