{"id":"096a25a4-36ce-5160-b2f9-398c6408e0e5","stable_key":"35ec55a7-323c-5c28-979e-3bdafe9d5769:huvec-il6","predicate":"decreases_in_recorded_experiment","statement":"C3G metabolite mixtures reduced IL-6 secretion at selected concentrations in HUVECs.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"c08643b0-7c6c-5b6a-8061-103915bb407d","mechanism_event_label":"C3G metabolite mixtures reduced IL-6 secretion at selected concentrations in HUVECs.","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":"cd114c85-932b-54a1-a6eb-9443c7b61561","slug":"human-huvec-il6-release","display_name":"IL-6 release by human umbilical-vein endothelial cells","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"c08643b0-7c6c-5b6a-8061-103915bb407d","stable_key":"35ec55a7-323c-5c28-979e-3bdafe9d5769:huvec-il6-event","event_type":"experimental_observation","label":"C3G metabolite mixtures reduced IL-6 secretion at selected concentrations in HUVECs.","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":"Metabolite signature plus TNF","sequence_order":0,"notes":""},{"entity":{"id":"cd114c85-932b-54a1-a6eb-9443c7b61561","slug":"human-huvec-il6-release","display_name":"IL-6 release by human umbilical-vein endothelial cells","entity_type_key":"cellular_process"},"role":"measured outcome","stoichiometry":null,"state_label":"decrease","sequence_order":1,"notes":""},{"entity":{"id":"ef8f8807-395d-5dc6-9693-70e90f41b268","slug":"il6","display_name":"IL6","entity_type_key":"cytokine"},"role":"measured cytokine","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\": \"Metabolite signature plus TNF\", \"comparator\": \"TNF plus vehicle\", \"endpoint\": \"C3G metabolite mixtures reduced IL-6 secretion at selected concentrations in HUVECs.\", \"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":"HUVEC; Figure 3; 24-hour TNF challenge at 10 ng/mL.","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":"The HUVEC effect was absent at the lowest mixture concentrations; HCAEC protein-release null remains separate from transcript results. Different cell types and TNF stimuli are not an unexplained literature conflict.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"C3G metabolite mixtures reduced IL-6 secretion at selected concentrations in HUVECs.","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":"ff818896-1916-55c5-ada8-e214f7c0559f","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":"HUVEC; Figure 3; 24-hour TNF challenge at 10 ng/mL.","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":"16a76e85-0dfc-55fc-8196-8f0eb317f29f","relation_type":"limits_scope_of","notes":"Different endothelial cells and TNF stimulus: do not generalize HUVEC IL-6 secretion to all endothelium.","source_claim_id":"3880b14f-5bcc-5456-8f9b-affe46e0d05e","source_claim_key":"35ec55a7-323c-5c28-979e-3bdafe9d5769:hcaec-il6-null","source_statement":"C3G metabolite mixtures did not significantly reduce IL-6 secretion in HCAECs.","target_claim_id":"096a25a4-36ce-5160-b2f9-398c6408e0e5","target_claim_key":"35ec55a7-323c-5c28-979e-3bdafe9d5769:huvec-il6","target_statement":"C3G metabolite mixtures reduced IL-6 secretion at selected concentrations in HUVECs."}],"conflicts":[],"corrections":[],"research":null}