Cyanidin 3-O-beta-D-glucopyranoside

evidence_access

Full text retrieved; relevant methods/results/figure text reviewed. No independent raw-data verification.

experimental_contrast

{"intervention": "50 uM cyanidin-3-glucoside", "comparator": "Untreated/vehicle-matched adipocytes in the corresponding assay", "endpoint": "In human omental adipocytes, 50 uM cyanidin-3-glucoside increased glucose uptake in the tested culture model.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.

experimental_model

Human omental adipocytes, 18-hour exposure; parallel mouse experiments are separate.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

High systemic-exposure model; roughly hundreds-fold above selected free-serum peaks. Does not establish dietary insulin replacement.

plain_language

In human omental adipocytes, 50 uM cyanidin-3-glucoside increased glucose uptake in the tested culture model.

primary_references

Cyanidin-3-O-β-glucoside and protocatechuic acid exert insulin-like effects by upregulating PPARγ activity in human omental adipocytes. | 2011 | DOI 10.2337/db10-1461 | PMID 21788573 | https://pubmed.ncbi.nlm.nih.gov/21788573/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC3161313/ | https://doi.org/10.2337/db10-1461

source_locator

Reviewed reference lines 70-70; exact primary location described in quoted passage where extracted.

Anthocyanins: detailed mechanisms of action (reviewed 4 October 2026) · lines 70–70

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. · supports · Human omental adipocytes, 18-hour exposure; parallel mouse experiments are separate. · source_derived_draft · unverified_draft

**Adipocyte glucose uptake involves PPARγ in one high-exposure model.** Human omental adipocytes exposed to 50 µM C3G or 100 µM PCA showed increased glucose uptake, GLUT4 recruitment and adiponectin-related responses. The decisive PPARγ silencing and antagonist experiments were performed in mouse 3T3-L1 adipocytes: disrupting PPARγ prevented polyphenol-associated GLUT4/adiponectin upregulation and GLUT4 recruitment. These mouse perturbations must not be relabeled human knockdowns. The human-cell concentrations are far above the selected free serum peaks in the tracer study; the experiment does not establish an insulin-like dietary effect. [Scazzocchio et al., 2011](https://pmc.ncbi.nlm.nih.gov/articles/PMC3161313/).

evidence_access

Full text retrieved; relevant methods/results/figure text reviewed. No independent raw-data verification.

experimental_contrast

{"intervention": "50 uM cyanidin-3-glucoside", "comparator": "Untreated/vehicle-matched adipocytes in the corresponding assay", "endpoint": "In human omental adipocytes, 50 uM cyanidin-3-glucoside increased GLUT4 membrane recruitment in the tested culture model.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.

experimental_model

Human omental adipocytes, 18-hour exposure; parallel mouse experiments are separate.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

High systemic-exposure model; roughly hundreds-fold above selected free-serum peaks. Does not establish dietary insulin replacement.

plain_language

In human omental adipocytes, 50 uM cyanidin-3-glucoside increased GLUT4 membrane recruitment in the tested culture model.

primary_references

Cyanidin-3-O-β-glucoside and protocatechuic acid exert insulin-like effects by upregulating PPARγ activity in human omental adipocytes. | 2011 | DOI 10.2337/db10-1461 | PMID 21788573 | https://pubmed.ncbi.nlm.nih.gov/21788573/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC3161313/ | https://doi.org/10.2337/db10-1461

source_locator

Reviewed reference lines 70-70; exact primary location described in quoted passage where extracted.

Anthocyanins: detailed mechanisms of action (reviewed 4 October 2026) · lines 70–70

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. · supports · Human omental adipocytes, 18-hour exposure; parallel mouse experiments are separate. · source_derived_draft · unverified_draft

**Adipocyte glucose uptake involves PPARγ in one high-exposure model.** Human omental adipocytes exposed to 50 µM C3G or 100 µM PCA showed increased glucose uptake, GLUT4 recruitment and adiponectin-related responses. The decisive PPARγ silencing and antagonist experiments were performed in mouse 3T3-L1 adipocytes: disrupting PPARγ prevented polyphenol-associated GLUT4/adiponectin upregulation and GLUT4 recruitment. These mouse perturbations must not be relabeled human knockdowns. The human-cell concentrations are far above the selected free serum peaks in the tracer study; the experiment does not establish an insulin-like dietary effect. [Scazzocchio et al., 2011](https://pmc.ncbi.nlm.nih.gov/articles/PMC3161313/).

evidence_access

Full text retrieved; relevant methods/results/figure text reviewed. No independent raw-data verification.

experimental_condition

TNF without test glucoside present · Tumor necrosis factor Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_condition

TNF without test glucoside present · Cyanidin 3-O-beta-D-glucopyranoside Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_contrast

{"intervention": "cyanidin-3-glucoside plus TNF", "comparator": "TNF without test glucoside", "endpoint": "cyanidin-3-glucoside limited TNF-induced barrier permeability, measured by electrical resistance and FITC-dextran flux.", "effect_direction": "decrease", "combination": "joint", "conditions": [{"entity_slug": "cyanidin-3-glucoside", "state": "present"}, {"entity_slug": "tnf", "state": "present"}]} Explicit extracted experimental comparison; source-derived draft.

experimental_model

Differentiated human Caco-2, 0.25-1 uM O-glucoside, TNF challenge; functional TEER and FITC-dextran readouts.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

Not generic class activity or clinical gut-disease treatment. Electrical resistance and tracer flux have opposite directions; claim direction describes permeability.

plain_language

cyanidin-3-glucoside limited TNF-induced barrier permeability, measured by electrical resistance and FITC-dextran flux.

primary_references

Anthocyanins inhibit tumor necrosis alpha-induced loss of Caco-2 cell barrier integrity. | 2017 | DOI 10.1039/c7fo00625j | PMID 28740990 | https://pubmed.ncbi.nlm.nih.gov/28740990/ | https://doi.org/10.1039/c7fo00625j | https://pubs.rsc.org/en/content/articlehtml/2017/fo/c7fo00625j

source_locator

Reviewed reference lines 78-78; exact primary location described in quoted passage where extracted.

Anthocyanins: detailed mechanisms of action (reviewed 4 October 2026) · lines 78–78

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. · supports · Differentiated human Caco-2, 0.25-1 uM O-glucoside, TNF challenge; functional TEER and FITC-dextran readouts. · source_derived_draft · unverified_draft

**Barrier protection is compound-selective.** In TNF-challenged human Caco-2 monolayers, cyanidin and delphinidin O-glucosides at 0.25–1 µM limited the fall in electrical resistance and rise in FITC-dextran permeability. Tested malvidin, peonidin and petunidin glucosides did not provide the same protection. NF-κB activation and downstream myosin-light-chain phosphorylation were reduced by the active compounds. This experiment measured functional permeability, not just more ZO-1 or occludin. It does not establish a clinical treatment for intestinal disease or a universal anthocyanin effect. [Cremonini et al., 2017](https://pubs.rsc.org/en/content/articlehtml/2017/fo/c7fo00625j).

evidence_access

Full text retrieved; relevant methods/results/figure text reviewed. No independent raw-data verification.

experimental_condition

TNF alone present · Tumor necrosis factor Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_condition

TNF alone present · Cyanidin 3-O-beta-D-glucopyranoside Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_contrast

{"intervention": "cyanidin-3-glucoside plus TNF", "comparator": "TNF alone", "endpoint": "The active glucoside reduced TNF-triggered downstream myosin-light-chain phosphorylation in the barrier experiment.", "effect_direction": "decrease", "combination": "joint", "conditions": [{"entity_slug": "cyanidin-3-glucoside", "state": "present"}, {"entity_slug": "tnf", "state": "present"}]} Explicit extracted experimental comparison; source-derived draft.

experimental_model

Human Caco-2 monolayers; 0.25-1 uM glucosides; NF-kappa-B and MLC signaling studied.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

Pathway evidence in cultured intestinal epithelium, not systemic NF-kappa-B suppression.

plain_language

The active glucoside reduced TNF-triggered downstream myosin-light-chain phosphorylation in the barrier experiment.

primary_references

Anthocyanins inhibit tumor necrosis alpha-induced loss of Caco-2 cell barrier integrity. | 2017 | DOI 10.1039/c7fo00625j | PMID 28740990 | https://pubmed.ncbi.nlm.nih.gov/28740990/ | https://doi.org/10.1039/c7fo00625j | https://pubs.rsc.org/en/content/articlehtml/2017/fo/c7fo00625j

source_locator

Reviewed reference lines 78-78; exact primary location described in quoted passage where extracted.

Anthocyanins: detailed mechanisms of action (reviewed 4 October 2026) · lines 78–78

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. · supports · Human Caco-2 monolayers; 0.25-1 uM glucosides; NF-kappa-B and MLC signaling studied. · source_derived_draft · unverified_draft

**Barrier protection is compound-selective.** In TNF-challenged human Caco-2 monolayers, cyanidin and delphinidin O-glucosides at 0.25–1 µM limited the fall in electrical resistance and rise in FITC-dextran permeability. Tested malvidin, peonidin and petunidin glucosides did not provide the same protection. NF-κB activation and downstream myosin-light-chain phosphorylation were reduced by the active compounds. This experiment measured functional permeability, not just more ZO-1 or occludin. It does not establish a clinical treatment for intestinal disease or a universal anthocyanin effect. [Cremonini et al., 2017](https://pubs.rsc.org/en/content/articlehtml/2017/fo/c7fo00625j).

evidence_access

Primary article abstract read in indexed publisher/author-hosted result; publisher full text unavailable. Exact pH series and extract/metal ratios not extracted.

experimental_model

Cell-free spectrophotometric metal assays; multiple pH and compound/metal ratios; exact series not extracted.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

Binding or reduction, not human absorption, intracellular stripping or ferroptosis prevention. Exact assay metal pools and doses require full methods.

plain_language

Purified cyanidin-3-glucoside reduced copper in the reported cell-free assays.

primary_references

Fruit extracts of 10 varieties of elderberry (Sambucus nigra L.) interact differently with iron and copper | 2016 | DOI 10.1016/j.phytol.2016.10.025 | https://doi.org/10.1016/j.phytol.2016.10.025

source_locator

Reviewed reference lines 88-88; exact primary location described in quoted passage where extracted.

Anthocyanins: detailed mechanisms of action (reviewed 4 October 2026) · lines 88–88

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. · supports · Cell-free spectrophotometric metal assays; multiple pH and compound/metal ratios; exact series not extracted. · source_derived_draft · unverified_draft

**Iron binding and metal reduction are different reactions.** Purified cyanidin, C3G and standardized elderberry extracts chelated iron and reduced iron and copper in cell-free assays; copper-chelating activity was relatively low. Extract behavior varied and was not completely explained by pigment concentration. Binding a metal, changing its oxidation state and reducing intestinal absorption are three different endpoints. This does not establish removal of intracellular metals or protection from ferroptosis in people. [Mladěnka et al., 2016](https://doi.org/10.1016/j.phytol.2016.10.025).

evidence_access

Primary article abstract read in indexed publisher/author-hosted result; publisher full text unavailable. Exact pH series and extract/metal ratios not extracted.

experimental_model

Cell-free spectrophotometric metal assays; multiple pH and compound/metal ratios; exact series not extracted.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

Binding or reduction, not human absorption, intracellular stripping or ferroptosis prevention. Exact assay metal pools and doses require full methods.

plain_language

Purified cyanidin-3-glucoside bound iron in the reported cell-free assays.

primary_references

Fruit extracts of 10 varieties of elderberry (Sambucus nigra L.) interact differently with iron and copper | 2016 | DOI 10.1016/j.phytol.2016.10.025 | https://doi.org/10.1016/j.phytol.2016.10.025

source_locator

Reviewed reference lines 88-88; exact primary location described in quoted passage where extracted.

Anthocyanins: detailed mechanisms of action (reviewed 4 October 2026) · lines 88–88

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. · supports · Cell-free spectrophotometric metal assays; multiple pH and compound/metal ratios; exact series not extracted. · source_derived_draft · unverified_draft

**Iron binding and metal reduction are different reactions.** Purified cyanidin, C3G and standardized elderberry extracts chelated iron and reduced iron and copper in cell-free assays; copper-chelating activity was relatively low. Extract behavior varied and was not completely explained by pigment concentration. Binding a metal, changing its oxidation state and reducing intestinal absorption are three different endpoints. This does not establish removal of intracellular metals or protection from ferroptosis in people. [Mladěnka et al., 2016](https://doi.org/10.1016/j.phytol.2016.10.025).

evidence_access

Primary article abstract read in indexed publisher/author-hosted result; publisher full text unavailable. Exact pH series and extract/metal ratios not extracted.

experimental_model

Cell-free spectrophotometric metal assays; multiple pH and compound/metal ratios; exact series not extracted.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

Binding or reduction, not human absorption, intracellular stripping or ferroptosis prevention. Exact assay metal pools and doses require full methods.

plain_language

Purified cyanidin-3-glucoside reduced iron in the reported cell-free assays.

primary_references

Fruit extracts of 10 varieties of elderberry (Sambucus nigra L.) interact differently with iron and copper | 2016 | DOI 10.1016/j.phytol.2016.10.025 | https://doi.org/10.1016/j.phytol.2016.10.025

source_locator

Reviewed reference lines 88-88; exact primary location described in quoted passage where extracted.

Anthocyanins: detailed mechanisms of action (reviewed 4 October 2026) · lines 88–88

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. · supports · Cell-free spectrophotometric metal assays; multiple pH and compound/metal ratios; exact series not extracted. · source_derived_draft · unverified_draft

**Iron binding and metal reduction are different reactions.** Purified cyanidin, C3G and standardized elderberry extracts chelated iron and reduced iron and copper in cell-free assays; copper-chelating activity was relatively low. Extract behavior varied and was not completely explained by pigment concentration. Binding a metal, changing its oxidation state and reducing intestinal absorption are three different endpoints. This does not establish removal of intracellular metals or protection from ferroptosis in people. [Mladěnka et al., 2016](https://doi.org/10.1016/j.phytol.2016.10.025).

evidence_access

Full text retrieved; relevant methods/results/figure text reviewed. No independent raw-data verification.

experimental_contrast

{"intervention": "50 uM cyanidin-3-glucoside", "comparator": "Cell assay without added glycoside", "endpoint": "The tested cyanidin glycoside reduced fluorescent glucose-analogue uptake in Caco-2 BBe1 cells at 50 uM.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.

experimental_model

Human Caco-2 BBe1; 50 uM flavonoid pretreatment, fluorescent 2-NBDG uptake; not dietary human glucose absorption.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

Fluorescent analogue outcome, not verified clinical glycemic benefit or carbohydrate deficiency.

plain_language

The tested cyanidin glycoside reduced fluorescent glucose-analogue uptake in Caco-2 BBe1 cells at 50 uM.

primary_references

Molecular Mechanisms Underlying the Absorption of Aglycone and Glycosidic Flavonoids in a Caco-2 BBe1 Cell Model. | 2020 | DOI 10.1021/acsomega.0c00379 | PMID 32455198 | https://pubmed.ncbi.nlm.nih.gov/32455198/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC7240828/ | https://doi.org/10.1021/acsomega.0c00379

source_locator

Reviewed reference lines 40-40; exact primary location described in quoted passage where extracted.

Anthocyanins: detailed mechanisms of action (reviewed 4 October 2026) · lines 40–40

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. · supports · Human Caco-2 BBe1; 50 uM flavonoid pretreatment, fluorescent 2-NBDG uptake; not dietary human glucose absorption. · source_derived_draft · unverified_draft

**Glucose handling is a separate cross-nutrient interaction.** A Caco-2 BBe1 study tested cyanidin and glycosides alongside quercetin compounds. At 50 µM, the glycosides reduced uptake of the fluorescent glucose analogue 2-NBDG. Transport inhibition and SGLT1 knockdown supported carrier involvement in glycoside uptake, with different behavior for aglycones. This is a nutrient-transport interaction in cultured cells; it is not proof that ordinary berry intake blocks intestinal glucose absorption or causes carbohydrate deficiency. [Zhang et al., 2020, transport and glucose-uptake experiments](https://pmc.ncbi.nlm.nih.gov/articles/PMC7240828/).

evidence_access

Full text retrieved; relevant methods/results/figure text reviewed. No independent raw-data verification.

experimental_model

Same human 500 mg tracer cohort; refer to the analyte-specific n, pooled isomers and peak times in Table 2.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

Tracer-derived product, not sole active payload. Different maxima cannot be summed into a simultaneous mixture. Shared metabolites retain independent identity and effects.

plain_language

After labeled C3G ingestion, Ferulic acid / 4-hydroxy-3-methoxycinnamic acid was detected as a labeled serum product with its own concentration-time profile.

primary_references

The pharmacokinetics of anthocyanins and their metabolites in humans. | 2014 | DOI 10.1111/bph.12676 | PMID 24602005 | https://pubmed.ncbi.nlm.nih.gov/24602005/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC4080980/ | https://doi.org/10.1111/bph.12676

source_locator

Reviewed reference lines 19-30; exact primary location described in quoted passage where extracted.

Anthocyanins: detailed mechanisms of action (reviewed 4 October 2026) · lines 19–30

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. · supports · Same human 500 mg tracer cohort; refer to the analyte-specific n, pooled isomers and peak times in Table 2. · source_derived_draft · unverified_draft

**Individual metabolites peak at different times.** A second analysis of the same tracer cohort reported the following selected serum values; these are means ± SEM, not universal target concentrations. The number of participants with quantifiable analyte differed by compound. [de Ferrars et al., 2014, Table 2](https://pmc.ncbi.nlm.nih.gov/articles/PMC4080980/). | Analyte | n | Peak, nM | Time to peak, hours | |---|---:|---:|---:| | C3G | 5 | 141 ± 70 | 1.8 ± 0.2 | | Protocatechuic acid (PCA) | 8 | 146 ± 74 | 3.3 ± 0.7 | | PCA sulfates, pooled isomers | 8 | 157 ± 116 | 11.4 ± 3.8 | | Vanillic acid | 2 | 1,845 ± 838 | 12.5 ± 11.5 | | Ferulic acid, B-ring label | 7 | 827 ± 371 | 8.2 ± 4.1 | | Hippuric acid | 8 | 1,962 ± 1,389 | 15.7 ± 4.1 | Free PCA and C3G therefore had similar mean peaks in this experiment. Vanillic acid's estimate came from only two participants. The values are distinct maxima, not a simultaneous mixture to be summed. Conjugated and unconjugated forms are separate exposures. A 50 µM PCA experiment is roughly 340 times this mean free-PCA peak; plasma comparisons still do not establish intestinal or intracellular concentrations. The two tracer publications are complementary analyses, not independent replications.

evidence_access

Full text retrieved; relevant methods/results/figure text reviewed. No independent raw-data verification.

experimental_model

Same human 500 mg tracer cohort; refer to the analyte-specific n, pooled isomers and peak times in Table 2.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

Tracer-derived product, not sole active payload. Different maxima cannot be summed into a simultaneous mixture. Shared metabolites retain independent identity and effects.

plain_language

After labeled C3G ingestion, Hippuric acid / benzoylglycine was detected as a labeled serum product with its own concentration-time profile.

primary_references

The pharmacokinetics of anthocyanins and their metabolites in humans. | 2014 | DOI 10.1111/bph.12676 | PMID 24602005 | https://pubmed.ncbi.nlm.nih.gov/24602005/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC4080980/ | https://doi.org/10.1111/bph.12676

source_locator

Reviewed reference lines 19-30; exact primary location described in quoted passage where extracted.

Anthocyanins: detailed mechanisms of action (reviewed 4 October 2026) · lines 19–30

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. · supports · Same human 500 mg tracer cohort; refer to the analyte-specific n, pooled isomers and peak times in Table 2. · source_derived_draft · unverified_draft

**Individual metabolites peak at different times.** A second analysis of the same tracer cohort reported the following selected serum values; these are means ± SEM, not universal target concentrations. The number of participants with quantifiable analyte differed by compound. [de Ferrars et al., 2014, Table 2](https://pmc.ncbi.nlm.nih.gov/articles/PMC4080980/). | Analyte | n | Peak, nM | Time to peak, hours | |---|---:|---:|---:| | C3G | 5 | 141 ± 70 | 1.8 ± 0.2 | | Protocatechuic acid (PCA) | 8 | 146 ± 74 | 3.3 ± 0.7 | | PCA sulfates, pooled isomers | 8 | 157 ± 116 | 11.4 ± 3.8 | | Vanillic acid | 2 | 1,845 ± 838 | 12.5 ± 11.5 | | Ferulic acid, B-ring label | 7 | 827 ± 371 | 8.2 ± 4.1 | | Hippuric acid | 8 | 1,962 ± 1,389 | 15.7 ± 4.1 | Free PCA and C3G therefore had similar mean peaks in this experiment. Vanillic acid's estimate came from only two participants. The values are distinct maxima, not a simultaneous mixture to be summed. Conjugated and unconjugated forms are separate exposures. A 50 µM PCA experiment is roughly 340 times this mean free-PCA peak; plasma comparisons still do not establish intestinal or intracellular concentrations. The two tracer publications are complementary analyses, not independent replications.

evidence_access

Full text retrieved; relevant methods/results/figure text reviewed. No independent raw-data verification.

experimental_model

Same human 500 mg tracer cohort; refer to the analyte-specific n, pooled isomers and peak times in Table 2.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

Tracer-derived product, not sole active payload. Different maxima cannot be summed into a simultaneous mixture. Shared metabolites retain independent identity and effects.

plain_language

After labeled C3G ingestion, Protocatechuic-acid sulfate isomers, unresolved assay sum was detected as a labeled serum product with its own concentration-time profile.

primary_references

The pharmacokinetics of anthocyanins and their metabolites in humans. | 2014 | DOI 10.1111/bph.12676 | PMID 24602005 | https://pubmed.ncbi.nlm.nih.gov/24602005/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC4080980/ | https://doi.org/10.1111/bph.12676

source_locator

Reviewed reference lines 19-30; exact primary location described in quoted passage where extracted.

Anthocyanins: detailed mechanisms of action (reviewed 4 October 2026) · lines 19–30

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. · supports · Same human 500 mg tracer cohort; refer to the analyte-specific n, pooled isomers and peak times in Table 2. · source_derived_draft · unverified_draft

**Individual metabolites peak at different times.** A second analysis of the same tracer cohort reported the following selected serum values; these are means ± SEM, not universal target concentrations. The number of participants with quantifiable analyte differed by compound. [de Ferrars et al., 2014, Table 2](https://pmc.ncbi.nlm.nih.gov/articles/PMC4080980/). | Analyte | n | Peak, nM | Time to peak, hours | |---|---:|---:|---:| | C3G | 5 | 141 ± 70 | 1.8 ± 0.2 | | Protocatechuic acid (PCA) | 8 | 146 ± 74 | 3.3 ± 0.7 | | PCA sulfates, pooled isomers | 8 | 157 ± 116 | 11.4 ± 3.8 | | Vanillic acid | 2 | 1,845 ± 838 | 12.5 ± 11.5 | | Ferulic acid, B-ring label | 7 | 827 ± 371 | 8.2 ± 4.1 | | Hippuric acid | 8 | 1,962 ± 1,389 | 15.7 ± 4.1 | Free PCA and C3G therefore had similar mean peaks in this experiment. Vanillic acid's estimate came from only two participants. The values are distinct maxima, not a simultaneous mixture to be summed. Conjugated and unconjugated forms are separate exposures. A 50 µM PCA experiment is roughly 340 times this mean free-PCA peak; plasma comparisons still do not establish intestinal or intracellular concentrations. The two tracer publications are complementary analyses, not independent replications.

evidence_access

Full text retrieved; relevant methods/results/figure text reviewed. No independent raw-data verification.

experimental_model

Same human 500 mg tracer cohort; refer to the analyte-specific n, pooled isomers and peak times in Table 2.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

Tracer-derived product, not sole active payload. Different maxima cannot be summed into a simultaneous mixture. Shared metabolites retain independent identity and effects.

plain_language

After labeled C3G ingestion, Vanillic acid / 4-hydroxy-3-methoxybenzoic acid was detected as a labeled serum product with its own concentration-time profile.

primary_references

The pharmacokinetics of anthocyanins and their metabolites in humans. | 2014 | DOI 10.1111/bph.12676 | PMID 24602005 | https://pubmed.ncbi.nlm.nih.gov/24602005/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC4080980/ | https://doi.org/10.1111/bph.12676

source_locator

Reviewed reference lines 19-30; exact primary location described in quoted passage where extracted.

Anthocyanins: detailed mechanisms of action (reviewed 4 October 2026) · lines 19–30

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. · supports · Same human 500 mg tracer cohort; refer to the analyte-specific n, pooled isomers and peak times in Table 2. · source_derived_draft · unverified_draft

**Individual metabolites peak at different times.** A second analysis of the same tracer cohort reported the following selected serum values; these are means ± SEM, not universal target concentrations. The number of participants with quantifiable analyte differed by compound. [de Ferrars et al., 2014, Table 2](https://pmc.ncbi.nlm.nih.gov/articles/PMC4080980/). | Analyte | n | Peak, nM | Time to peak, hours | |---|---:|---:|---:| | C3G | 5 | 141 ± 70 | 1.8 ± 0.2 | | Protocatechuic acid (PCA) | 8 | 146 ± 74 | 3.3 ± 0.7 | | PCA sulfates, pooled isomers | 8 | 157 ± 116 | 11.4 ± 3.8 | | Vanillic acid | 2 | 1,845 ± 838 | 12.5 ± 11.5 | | Ferulic acid, B-ring label | 7 | 827 ± 371 | 8.2 ± 4.1 | | Hippuric acid | 8 | 1,962 ± 1,389 | 15.7 ± 4.1 | Free PCA and C3G therefore had similar mean peaks in this experiment. Vanillic acid's estimate came from only two participants. The values are distinct maxima, not a simultaneous mixture to be summed. Conjugated and unconjugated forms are separate exposures. A 50 µM PCA experiment is roughly 340 times this mean free-PCA peak; plasma comparisons still do not establish intestinal or intracellular concentrations. The two tracer publications are complementary analyses, not independent replications.

evidence_access

Full text retrieved; relevant methods/results/figure text reviewed. No independent raw-data verification.

experimental_model

Same eight-men cohort as Czank 2013; analyte-specific n=5, mean +/- SEM.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.

plain_language

The tracer cohort had mean serum C3G Cmax 141 +/- 70 nM at 1.8 +/- 0.2 hours, measurable in five participants.

primary_references

The pharmacokinetics of anthocyanins and their metabolites in humans. | 2014 | DOI 10.1111/bph.12676 | PMID 24602005 | https://pubmed.ncbi.nlm.nih.gov/24602005/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC4080980/ | https://doi.org/10.1111/bph.12676

source_locator

Reviewed reference lines 19-30; exact primary location described in quoted passage where extracted.

Anthocyanins: detailed mechanisms of action (reviewed 4 October 2026) · lines 19–30

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. · supports · Same eight-men cohort as Czank 2013; analyte-specific n=5, mean +/- SEM. · source_derived_draft · unverified_draft

**Individual metabolites peak at different times.** A second analysis of the same tracer cohort reported the following selected serum values; these are means ± SEM, not universal target concentrations. The number of participants with quantifiable analyte differed by compound. [de Ferrars et al., 2014, Table 2](https://pmc.ncbi.nlm.nih.gov/articles/PMC4080980/). | Analyte | n | Peak, nM | Time to peak, hours | |---|---:|---:|---:| | C3G | 5 | 141 ± 70 | 1.8 ± 0.2 | | Protocatechuic acid (PCA) | 8 | 146 ± 74 | 3.3 ± 0.7 | | PCA sulfates, pooled isomers | 8 | 157 ± 116 | 11.4 ± 3.8 | | Vanillic acid | 2 | 1,845 ± 838 | 12.5 ± 11.5 | | Ferulic acid, B-ring label | 7 | 827 ± 371 | 8.2 ± 4.1 | | Hippuric acid | 8 | 1,962 ± 1,389 | 15.7 ± 4.1 | Free PCA and C3G therefore had similar mean peaks in this experiment. Vanillic acid's estimate came from only two participants. The values are distinct maxima, not a simultaneous mixture to be summed. Conjugated and unconjugated forms are separate exposures. A 50 µM PCA experiment is roughly 340 times this mean free-PCA peak; plasma comparisons still do not establish intestinal or intracellular concentrations. The two tracer publications are complementary analyses, not independent replications.

evidence_access

Full text retrieved; relevant methods/results/figure text reviewed. No independent raw-data verification.

experimental_model

Human 500 mg labeled C3G bolus; plasma chemical measurement, not a biological efficacy test.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

Specific tracer-supported precursor/product relationship; does not assign every PCA effect to C3G or identify all microbial versus nonmicrobial formation.

plain_language

Labeled C3G produced circulating labeled PCA in humans; mean free PCA Cmax was 146 +/- 74 nM, n=8.

primary_references

The pharmacokinetics of anthocyanins and their metabolites in humans. | 2014 | DOI 10.1111/bph.12676 | PMID 24602005 | https://pubmed.ncbi.nlm.nih.gov/24602005/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC4080980/ | https://doi.org/10.1111/bph.12676

source_locator

Reviewed reference lines 19-30; exact primary location described in quoted passage where extracted.

Anthocyanins: detailed mechanisms of action (reviewed 4 October 2026) · lines 19–30

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. · supports · Human 500 mg labeled C3G bolus; plasma chemical measurement, not a biological efficacy test. · source_derived_draft · unverified_draft

**Individual metabolites peak at different times.** A second analysis of the same tracer cohort reported the following selected serum values; these are means ± SEM, not universal target concentrations. The number of participants with quantifiable analyte differed by compound. [de Ferrars et al., 2014, Table 2](https://pmc.ncbi.nlm.nih.gov/articles/PMC4080980/). | Analyte | n | Peak, nM | Time to peak, hours | |---|---:|---:|---:| | C3G | 5 | 141 ± 70 | 1.8 ± 0.2 | | Protocatechuic acid (PCA) | 8 | 146 ± 74 | 3.3 ± 0.7 | | PCA sulfates, pooled isomers | 8 | 157 ± 116 | 11.4 ± 3.8 | | Vanillic acid | 2 | 1,845 ± 838 | 12.5 ± 11.5 | | Ferulic acid, B-ring label | 7 | 827 ± 371 | 8.2 ± 4.1 | | Hippuric acid | 8 | 1,962 ± 1,389 | 15.7 ± 4.1 | Free PCA and C3G therefore had similar mean peaks in this experiment. Vanillic acid's estimate came from only two participants. The values are distinct maxima, not a simultaneous mixture to be summed. Conjugated and unconjugated forms are separate exposures. A 50 µM PCA experiment is roughly 340 times this mean free-PCA peak; plasma comparisons still do not establish intestinal or intracellular concentrations. The two tracer publications are complementary analyses, not independent replications.

evidence_access

Primary indexed abstract reviewed; full methods, figures, exact doses or endpoint-specific species assignments may remain unextracted.

experimental_model

Eight healthy men, single oral 500 mg 13C5-C3G, 48-hour sampling.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.

plain_language

After 500 mg labeled C3G in eight men, urine plus breath contained 12.38% of administered label over 48 hours; this is not intact C3G recovery.

primary_references

Human metabolism and elimination of the anthocyanin, cyanidin-3-glucoside: a (13)C-tracer study. | 2013 | DOI 10.3945/ajcn.112.049247 | PMID 23604435 | https://pubmed.ncbi.nlm.nih.gov/23604435/ | https://doi.org/10.3945/ajcn.112.049247

source_locator

Reviewed reference lines 17-17; exact primary location described in quoted passage where extracted.

Anthocyanins: detailed mechanisms of action (reviewed 4 October 2026) · lines 17–17

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. · supports · Eight healthy men, single oral 500 mg 13C5-C3G, 48-hour sampling. · source_derived_draft · unverified_draft

**Tracer recovery is not intact-pigment bioavailability.** Eight men received 500 mg of isotopically labeled cyanidin-3-glucoside (C3G), with sampling over 48 hours. The reported 12.38 ± 1.38% relative bioavailability comprised labeled carbon recovered in urine and breath: 5.37 ± 0.67% and 6.91 ± 1.59%, respectively. It is not 12.38% intact C3G, nor 12.38% pharmacologically active material. Combined labeled serum metabolites peaked at approximately 5.97 µM around 10.25 hours. Low urinary recovery of unchanged pigment cannot quantify total absorption. [Czank et al., 2013](https://pubmed.ncbi.nlm.nih.gov/23604435/).

evidence_access

Primary indexed abstract reviewed; full methods, figures, exact doses or endpoint-specific species assignments may remain unextracted.

experimental_model

Ten-compound chemical stability study in DMEM and water.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

Relative structural trends; no common plasma half-life or exact intracellular exposure inferred.

plain_language

Anthocyanin structure changes parent stability during DMEM incubation at pH 7.4, 37 C and 5% CO2.

primary_references

Structure-stability relationship of anthocyanins under cell culture condition. | 2019 | DOI 10.1080/09637486.2018.1506753 | PMID 30160540 | https://pubmed.ncbi.nlm.nih.gov/30160540/ | https://doi.org/10.1080/09637486.2018.1506753

source_locator

Reviewed reference lines 13-13; exact primary location described in quoted passage where extracted.

Anthocyanins: detailed mechanisms of action (reviewed 4 October 2026) · lines 13–13

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. · supports · Ten-compound chemical stability study in DMEM and water. · source_derived_draft · unverified_draft

**Culture medium changes the exposure.** A ten-compound study in DMEM at 37 °C, pH 7.4 and 5% CO2 found structure-dependent losses: glycosylation and B-ring methylation generally improved stability, while additional B-ring hydroxylation reduced it. Water and DMEM were not interchangeable. A nominal parent-compound dose maintained for hours may become a changing mixture; chemical measurements should accompany the biological assay. A flavylium charge under acidic conditions also does not establish selective mitochondrial delivery in living humans. [Zhang and colleagues, 2018](https://pubmed.ncbi.nlm.nih.gov/30160540/).

evidence_access

Primary article abstract read in indexed publisher/author-hosted result; publisher full text unavailable. Exact pH series and extract/metal ratios not extracted.

experimental_model

Cell-free standardized spectrophotometric comparisons.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

Low is not zero. Does not establish a clinical copper-depleting effect; extract composition and pH matter.

plain_language

The tested cyanidin compounds and elderberry preparations had low copper-chelating activity despite their metal-reducing reactions.

primary_references

Fruit extracts of 10 varieties of elderberry (Sambucus nigra L.) interact differently with iron and copper | 2016 | DOI 10.1016/j.phytol.2016.10.025 | https://doi.org/10.1016/j.phytol.2016.10.025

source_locator

Reviewed reference lines 88-88; exact primary location described in quoted passage where extracted.

Anthocyanins: detailed mechanisms of action (reviewed 4 October 2026) · lines 88–88

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. · supports · Cell-free standardized spectrophotometric comparisons. · source_derived_draft · unverified_draft

**Iron binding and metal reduction are different reactions.** Purified cyanidin, C3G and standardized elderberry extracts chelated iron and reduced iron and copper in cell-free assays; copper-chelating activity was relatively low. Extract behavior varied and was not completely explained by pigment concentration. Binding a metal, changing its oxidation state and reducing intestinal absorption are three different endpoints. This does not establish removal of intracellular metals or protection from ferroptosis in people. [Mladěnka et al., 2016](https://doi.org/10.1016/j.phytol.2016.10.025).

evidence_access

Full text retrieved; relevant methods/results/figure text reviewed. No independent raw-data verification.

experimental_model

In vitro mixtures reconstructed with authentic standards from a human tracer cohort.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

Preparation provenance does not attribute every component effect to the parent or transfer unrelated metabolite findings.

plain_language

The tested signatures reconstruct serum metabolite profiles measured after labeled C3G exposure; they are separate mixtures, not intact C3G.

primary_references

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

source_locator

Reviewed reference lines 58-58; exact primary location described in quoted passage where extracted.

Anthocyanins: detailed mechanisms of action (reviewed 4 October 2026) · lines 58–58

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. · supports · In vitro mixtures reconstructed with authentic standards from a human tracer cohort. · source_derived_draft · unverified_draft

**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/).

evidence_access

Primary indexed abstract reviewed; full methods, figures, exact doses or endpoint-specific species assignments may remain unextracted.

experimental_contrast

{"intervention": "C3G feeding in mice with the relevant microbiota condition", "comparator": "Matched control feeding", "endpoint": "C3G consumption reduced atherosclerotic lesion burden in the microbiota-dependent ApoE-deficient mouse setting.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.

experimental_model

ApoE-deficient mouse feeding experiment; antibiotics and microbiota reacquisition used to investigate dependence.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

Diet dose/duration not extracted from accessible abstract. Antibiotics are not selective blockade of a single metabolic step; no human plaque regression inferred.

plain_language

C3G consumption reduced atherosclerotic lesion burden in the microbiota-dependent ApoE-deficient mouse setting.

primary_references

Gut microbiota metabolism of anthocyanin promotes reverse cholesterol transport in mice via repressing miRNA-10b. | 2012 | DOI 10.1161/circresaha.112.266502 | PMID 22821931 | https://pubmed.ncbi.nlm.nih.gov/22821931/ | https://doi.org/10.1161/circresaha.112.266502

source_locator

Reviewed reference lines 66-66; exact primary location described in quoted passage where extracted.

Anthocyanins: detailed mechanisms of action (reviewed 4 October 2026) · lines 66–66

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. · supports · ApoE-deficient mouse feeding experiment; antibiotics and microbiota reacquisition used to investigate dependence. · source_derived_draft · unverified_draft

**PCA–miR-10b–cholesterol export is a specific experimental branch.** In ApoE-deficient mice, antibiotic depletion and microbiota reacquisition supported microbial involvement in C3G-to-PCA metabolism. PCA reduced macrophage miR-10b; functional tests showed miR-10b repressing ABCA1 and ABCG1 and limiting cholesterol efflux. PCA, unlike C3G at the compared concentrations, increased transporter expression and efflux. C3G feeding promoted macrophage reverse cholesterol transport and lesion regression in the microbiota-dependent mouse setting. The accessible primary abstract reports human- and mouse-derived macrophage experiments but does not fully separate every endpoint by species or list all doses; those remain extraction limits. [Wang et al., 2012](https://pubmed.ncbi.nlm.nih.gov/22821931/).

evidence_access

Primary indexed abstract reviewed; full methods, figures, exact doses or endpoint-specific species assignments may remain unextracted.

experimental_contrast

{"intervention": "C3G feeding in mice with the relevant microbiota condition", "comparator": "Matched control feeding", "endpoint": "C3G consumption promoted macrophage reverse cholesterol transport in the microbiota-dependent ApoE-deficient mouse setting.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.

experimental_model

ApoE-deficient mouse feeding experiment; antibiotics and microbiota reacquisition used to investigate dependence.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

Diet dose/duration not extracted from accessible abstract. Antibiotics are not selective blockade of a single metabolic step; no human plaque regression inferred.

plain_language

C3G consumption promoted macrophage reverse cholesterol transport in the microbiota-dependent ApoE-deficient mouse setting.

primary_references

Gut microbiota metabolism of anthocyanin promotes reverse cholesterol transport in mice via repressing miRNA-10b. | 2012 | DOI 10.1161/circresaha.112.266502 | PMID 22821931 | https://pubmed.ncbi.nlm.nih.gov/22821931/ | https://doi.org/10.1161/circresaha.112.266502

source_locator

Reviewed reference lines 66-66; exact primary location described in quoted passage where extracted.

Anthocyanins: detailed mechanisms of action (reviewed 4 October 2026) · lines 66–66

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. · supports · ApoE-deficient mouse feeding experiment; antibiotics and microbiota reacquisition used to investigate dependence. · source_derived_draft · unverified_draft

**PCA–miR-10b–cholesterol export is a specific experimental branch.** In ApoE-deficient mice, antibiotic depletion and microbiota reacquisition supported microbial involvement in C3G-to-PCA metabolism. PCA reduced macrophage miR-10b; functional tests showed miR-10b repressing ABCA1 and ABCG1 and limiting cholesterol efflux. PCA, unlike C3G at the compared concentrations, increased transporter expression and efflux. C3G feeding promoted macrophage reverse cholesterol transport and lesion regression in the microbiota-dependent mouse setting. The accessible primary abstract reports human- and mouse-derived macrophage experiments but does not fully separate every endpoint by species or list all doses; those remain extraction limits. [Wang et al., 2012](https://pubmed.ncbi.nlm.nih.gov/22821931/).

evidence_access

Primary indexed abstract reviewed; full methods, figures, exact doses or endpoint-specific species assignments may remain unextracted.

experimental_condition

Palmitate challenge without C3G challenge · Palmitate / hexadecanoate Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_condition

Palmitate challenge without C3G present · Cyanidin 3-O-beta-D-glucopyranoside Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_condition

Palmitate challenge without C3G signaling stimulus · Insulin Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_contrast

{"intervention": "C3G pretreatment followed by palmitate challenge", "comparator": "Palmitate challenge without C3G", "endpoint": "C3G pretreatment improved IRS1/PI3K/Akt insulin signaling in palmitate-challenged human endothelial cells.", "effect_direction": "increase", "combination": "joint", "conditions": [{"entity_slug": "cyanidin-3-glucoside", "state": "present"}, {"entity_slug": "palmitate", "state": "challenge"}, {"entity_slug": "insulin", "state": "signaling stimulus"}]} Explicit extracted experimental comparison; source-derived draft.

experimental_model

Palmitate-challenged HUVECs; accessible primary abstract; exact C3G dose/timing not extracted.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

Context-specific signaling rescue; no claim of direct KEAP1 binding or dietary circulating-metabolite effect.

plain_language

C3G pretreatment improved IRS1/PI3K/Akt insulin signaling in palmitate-challenged human endothelial cells.

primary_references

Cyanidin-3-O-glucoside ameliorates palmitate-induced insulin resistance by modulating IRS-1 phosphorylation and release of endothelial derived vasoactive factors. | 2017 | DOI 10.1016/j.bbalip.2016.12.008 | PMID 28011403 | https://pubmed.ncbi.nlm.nih.gov/28011403/ | https://doi.org/10.1016/j.bbalip.2016.12.008

source_locator

Reviewed reference lines 72-72; exact primary location described in quoted passage where extracted.

Anthocyanins: detailed mechanisms of action (reviewed 4 October 2026) · lines 72–72

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. · supports · Palmitate-challenged HUVECs; accessible primary abstract; exact C3G dose/timing not extracted. · source_derived_draft · unverified_draft

**Nrf2 dependence has been tested, but is context-specific.** C3G pretreatment in palmitate-challenged human endothelial cells improved IRS-1/PI3K/Akt-related insulin signaling and restored eNOS expression and NO release. Nrf2 silencing impaired the protective response. This is stronger than merely observing an antioxidant-gene increase, but neither direct KEAP1 binding nor the same action of circulating conjugates follows. The source's exact exposure protocol must accompany any quantitative reuse; only its accessible abstract was extracted here. [Fratantonio et al., 2017](https://pubmed.ncbi.nlm.nih.gov/28011403/).

evidence_access

Primary indexed abstract reviewed; full methods, figures, exact doses or endpoint-specific species assignments may remain unextracted.

experimental_condition

Palmitate challenge without C3G challenge · Palmitate / hexadecanoate Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_condition

Palmitate challenge without C3G present · Cyanidin 3-O-beta-D-glucopyranoside Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_condition

Palmitate challenge without C3G signaling stimulus · Insulin Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_contrast

{"intervention": "C3G pretreatment followed by palmitate challenge", "comparator": "Palmitate challenge without C3G", "endpoint": "C3G pretreatment improved NO release in palmitate-challenged human endothelial cells.", "effect_direction": "increase", "combination": "joint", "conditions": [{"entity_slug": "cyanidin-3-glucoside", "state": "present"}, {"entity_slug": "palmitate", "state": "challenge"}, {"entity_slug": "insulin", "state": "signaling stimulus"}]} Explicit extracted experimental comparison; source-derived draft.

experimental_model

Palmitate-challenged HUVECs; accessible primary abstract; exact C3G dose/timing not extracted.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

Context-specific signaling rescue; no claim of direct KEAP1 binding or dietary circulating-metabolite effect.

plain_language

C3G pretreatment improved NO release in palmitate-challenged human endothelial cells.

primary_references

Cyanidin-3-O-glucoside ameliorates palmitate-induced insulin resistance by modulating IRS-1 phosphorylation and release of endothelial derived vasoactive factors. | 2017 | DOI 10.1016/j.bbalip.2016.12.008 | PMID 28011403 | https://pubmed.ncbi.nlm.nih.gov/28011403/ | https://doi.org/10.1016/j.bbalip.2016.12.008

source_locator

Reviewed reference lines 72-72; exact primary location described in quoted passage where extracted.

Anthocyanins: detailed mechanisms of action (reviewed 4 October 2026) · lines 72–72

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. · supports · Palmitate-challenged HUVECs; accessible primary abstract; exact C3G dose/timing not extracted. · source_derived_draft · unverified_draft

**Nrf2 dependence has been tested, but is context-specific.** C3G pretreatment in palmitate-challenged human endothelial cells improved IRS-1/PI3K/Akt-related insulin signaling and restored eNOS expression and NO release. Nrf2 silencing impaired the protective response. This is stronger than merely observing an antioxidant-gene increase, but neither direct KEAP1 binding nor the same action of circulating conjugates follows. The source's exact exposure protocol must accompany any quantitative reuse; only its accessible abstract was extracted here. [Fratantonio et al., 2017](https://pubmed.ncbi.nlm.nih.gov/28011403/).

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary indexed abstract reviewed; full methods, figures, exact doses or endpoint-specific species assignments may remain unextracted.

experimental_condition

C3G/palmitate experiment with Nrf2 retained challenge · Palmitate / hexadecanoate Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_condition

C3G/palmitate experiment with Nrf2 retained present · Cyanidin 3-O-beta-D-glucopyranoside Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_condition

C3G/palmitate experiment with Nrf2 retained signaling stimulus · Insulin Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_condition

C3G/palmitate experiment with Nrf2 retained silenced · Human Nrf2 / NFE2L2 Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_contrast

{"intervention": "C3G/palmitate experiment with Nrf2 silencing", "comparator": "C3G/palmitate experiment with Nrf2 retained", "endpoint": "Nrf2 silencing impaired C3G-associated protection in the palmitate-challenged endothelial model.", "effect_direction": "decrease", "combination": "joint", "conditions": [{"entity_slug": "cyanidin-3-glucoside", "state": "present"}, {"entity_slug": "nfe2l2", "state": "silenced"}, {"entity_slug": "palmitate", "state": "challenge"}, {"entity_slug": "insulin", "state": "signaling stimulus"}]} Explicit extracted experimental comparison; source-derived draft.

experimental_model

HUVECs with Nrf2 transcript silencing and palmitate challenge.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

Exact experimental details remain abstract-level; no clinical cofactor-rescue claim.

plain_language

Nrf2 silencing impaired C3G-associated protection in the palmitate-challenged endothelial model.

primary_references

Cyanidin-3-O-glucoside ameliorates palmitate-induced insulin resistance by modulating IRS-1 phosphorylation and release of endothelial derived vasoactive factors. | 2017 | DOI 10.1016/j.bbalip.2016.12.008 | PMID 28011403 | https://pubmed.ncbi.nlm.nih.gov/28011403/ | https://doi.org/10.1016/j.bbalip.2016.12.008

source_locator

Reviewed reference lines 72-72; exact primary location described in quoted passage where extracted.

trigger_kind

machinery_impairment Imported condition classification; unverified.

Anthocyanins: detailed mechanisms of action (reviewed 4 October 2026) · lines 72–72

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. · supports · HUVECs with Nrf2 transcript silencing and palmitate challenge. · source_derived_draft · unverified_draft

**Nrf2 dependence has been tested, but is context-specific.** C3G pretreatment in palmitate-challenged human endothelial cells improved IRS-1/PI3K/Akt-related insulin signaling and restored eNOS expression and NO release. Nrf2 silencing impaired the protective response. This is stronger than merely observing an antioxidant-gene increase, but neither direct KEAP1 binding nor the same action of circulating conjugates follows. The source's exact exposure protocol must accompany any quantitative reuse; only its accessible abstract was extracted here. [Fratantonio et al., 2017](https://pubmed.ncbi.nlm.nih.gov/28011403/).

evidence_access

Primary indexed abstract reviewed; full methods, figures, exact doses or endpoint-specific species assignments may remain unextracted.

experimental_model

Purified anthocyanin aqueous-solution kinetics; exact compound and pH dependence.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.

plain_language

Solution pH changes reversible molecular-form transitions of the tested anthocyanin glucosides; degradation is a separate process.

primary_references

A New Insight into the Degradation of Anthocyanins: Reversible versus the Irreversible Chemical Processes. | 2022 | DOI 10.1021/acs.jafc.1c06521 | PMID 34982560 | https://pubmed.ncbi.nlm.nih.gov/34982560/ | https://doi.org/10.1021/acs.jafc.1c06521

source_locator

Reviewed reference lines 11-11; exact primary location described in quoted passage where extracted.

Anthocyanins: detailed mechanisms of action (reviewed 4 October 2026) · lines 11–11

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. · supports · Purified anthocyanin aqueous-solution kinetics; exact compound and pH dependence. · source_derived_draft · unverified_draft

**pH changes molecular form.** Experiments with four purified 3-O-glucosides distinguish reversible proton transfer, hydration and cis/trans isomerization from irreversible degradation. Flavylium, quinoidal, hemiketal and chalcone states are a reaction network whose populations and rates depend on the particular compound and solution. Color loss alone cannot identify the reaction. Neither one universal form at blood pH nor one universal plasma half-life follows from these solution experiments. [Sousa and colleagues, 2022](https://pubmed.ncbi.nlm.nih.gov/34982560/).

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Full text retrieved; relevant methods/results/figure text reviewed. No independent raw-data verification.

experimental_condition

cyanidin-3-glucoside with functional mouse Pparg present · Cyanidin 3-O-beta-D-glucopyranoside Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_condition

cyanidin-3-glucoside with functional mouse Pparg inhibited or silenced · Mouse peroxisome proliferator-activated receptor gamma / Pparg Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_contrast

{"intervention": "cyanidin-3-glucoside with mouse Pparg inhibition/silencing", "comparator": "cyanidin-3-glucoside with functional mouse Pparg", "endpoint": "PPARgamma inhibition or silencing blocked the polyphenol-associated GLUT4 recruitment in mouse 3T3-L1 adipocytes.", "effect_direction": "decrease", "combination": "joint", "conditions": [{"entity_slug": "cyanidin-3-glucoside", "state": "present"}, {"entity_slug": "mouse-pparg", "state": "inhibited or silenced"}]} Explicit extracted experimental comparison; source-derived draft.

experimental_model

Mouse 3T3-L1, Figure 7: mouse Pparg siRNA/scrambled comparison and GW9662 antagonist; 10 uM C3G or 100 uM PCA.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

Mouse perturbation, not a human knockdown. Supports pathway involvement, not direct binding affinity or clinical supplementation efficacy.

plain_language

PPARgamma inhibition or silencing blocked the polyphenol-associated GLUT4 recruitment in mouse 3T3-L1 adipocytes.

primary_references

Cyanidin-3-O-β-glucoside and protocatechuic acid exert insulin-like effects by upregulating PPARγ activity in human omental adipocytes. | 2011 | DOI 10.2337/db10-1461 | PMID 21788573 | https://pubmed.ncbi.nlm.nih.gov/21788573/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC3161313/ | https://doi.org/10.2337/db10-1461

source_locator

Reviewed reference lines 70-70; exact primary location described in quoted passage where extracted.

trigger_kind

machinery_impairment Imported condition classification; unverified.

Anthocyanins: detailed mechanisms of action (reviewed 4 October 2026) · lines 70–70

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. · supports · Mouse 3T3-L1, Figure 7: mouse Pparg siRNA/scrambled comparison and GW9662 antagonist; 10 uM C3G or 100 uM PCA. · source_derived_draft · unverified_draft

**Adipocyte glucose uptake involves PPARγ in one high-exposure model.** Human omental adipocytes exposed to 50 µM C3G or 100 µM PCA showed increased glucose uptake, GLUT4 recruitment and adiponectin-related responses. The decisive PPARγ silencing and antagonist experiments were performed in mouse 3T3-L1 adipocytes: disrupting PPARγ prevented polyphenol-associated GLUT4/adiponectin upregulation and GLUT4 recruitment. These mouse perturbations must not be relabeled human knockdowns. The human-cell concentrations are far above the selected free serum peaks in the tracer study; the experiment does not establish an insulin-like dietary effect. [Scazzocchio et al., 2011](https://pmc.ncbi.nlm.nih.gov/articles/PMC3161313/).

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Full text retrieved; relevant methods/results/figure text reviewed. No independent raw-data verification.

experimental_condition

C3G exposure with scrambled siRNA siRNA knockdown · Human glucose transporter 2 / SLC2A2 / GLUT2 Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_condition

C3G exposure with scrambled siRNA present · Cyanidin 3-O-beta-D-glucopyranoside Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_contrast

{"intervention": "C3G exposure with SLC2A2 siRNA", "comparator": "C3G exposure with scrambled siRNA", "endpoint": "Knocking down SLC2A2 reduced C3G transport in differentiated human Caco-2 monolayers relative to scrambled siRNA.", "effect_direction": "decrease", "combination": "joint", "conditions": [{"entity_slug": "slc2a2", "state": "siRNA knockdown"}, {"entity_slug": "cyanidin-3-glucoside", "state": "present"}]} Explicit extracted experimental comparison; source-derived draft.

experimental_model

Differentiated human Caco-2; 10-40 uM C3G transport experiments up to 120 min; siRNA comparison.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

Knockdown result, not a wild-type inhibitory action of the transporter. Does not quantify its contribution to human in vivo absorption.

plain_language

Knocking down SLC2A2 reduced C3G transport in differentiated human Caco-2 monolayers relative to scrambled siRNA.

primary_references

The role of sodium-dependent glucose transporter 1 and glucose transporter 2 in the absorption of cyanidin-3-o-β-glucoside in Caco-2 cells. | 2014 | DOI 10.3390/nu6104165 | PMID 25314643 | https://pubmed.ncbi.nlm.nih.gov/25314643/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC4210911/ | https://doi.org/10.3390/nu6104165

source_locator

Reviewed reference lines 38-38; exact primary location described in quoted passage where extracted.

trigger_kind

machinery_impairment Imported condition classification; unverified.

Anthocyanins: detailed mechanisms of action (reviewed 4 October 2026) · lines 38–38

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. · supports · Differentiated human Caco-2; 10-40 uM C3G transport experiments up to 120 min; siRNA comparison. · source_derived_draft · unverified_draft

**SGLT1 and GLUT2 have experimental support.** In differentiated human Caco-2 monolayers, pharmacological inhibition and separate SGLT1 or GLUT2 siRNA reduced C3G transport. Transport was examined across 10–40 µM C3G and up to 120 minutes; scrambled siRNA provided a comparator. This supports involvement in that epithelial model, not an exclusive absorption route or a measured contribution in the human intestine. Canonical proteins are SLC5A1/SGLT1 and SLC2A2/GLUT2. [Zou et al., 2014](https://pmc.ncbi.nlm.nih.gov/articles/PMC4210911/).

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Full text retrieved; relevant methods/results/figure text reviewed. No independent raw-data verification.

experimental_condition

C3G exposure with scrambled siRNA present · Cyanidin 3-O-beta-D-glucopyranoside Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_condition

C3G exposure with scrambled siRNA siRNA knockdown · Human sodium/glucose cotransporter SGLT1 / SLC5A1 Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_contrast

{"intervention": "C3G exposure with SLC5A1 siRNA", "comparator": "C3G exposure with scrambled siRNA", "endpoint": "Knocking down SLC5A1 reduced C3G transport in differentiated human Caco-2 monolayers relative to scrambled siRNA.", "effect_direction": "decrease", "combination": "joint", "conditions": [{"entity_slug": "slc5a1", "state": "siRNA knockdown"}, {"entity_slug": "cyanidin-3-glucoside", "state": "present"}]} Explicit extracted experimental comparison; source-derived draft.

experimental_model

Differentiated human Caco-2; 10-40 uM C3G transport experiments up to 120 min; siRNA comparison.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

Knockdown result, not a wild-type inhibitory action of the transporter. Does not quantify its contribution to human in vivo absorption.

plain_language

Knocking down SLC5A1 reduced C3G transport in differentiated human Caco-2 monolayers relative to scrambled siRNA.

primary_references

The role of sodium-dependent glucose transporter 1 and glucose transporter 2 in the absorption of cyanidin-3-o-β-glucoside in Caco-2 cells. | 2014 | DOI 10.3390/nu6104165 | PMID 25314643 | https://pubmed.ncbi.nlm.nih.gov/25314643/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC4210911/ | https://doi.org/10.3390/nu6104165

source_locator

Reviewed reference lines 38-38; exact primary location described in quoted passage where extracted.

trigger_kind

machinery_impairment Imported condition classification; unverified.

Anthocyanins: detailed mechanisms of action (reviewed 4 October 2026) · lines 38–38

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. · supports · Differentiated human Caco-2; 10-40 uM C3G transport experiments up to 120 min; siRNA comparison. · source_derived_draft · unverified_draft

**SGLT1 and GLUT2 have experimental support.** In differentiated human Caco-2 monolayers, pharmacological inhibition and separate SGLT1 or GLUT2 siRNA reduced C3G transport. Transport was examined across 10–40 µM C3G and up to 120 minutes; scrambled siRNA provided a comparator. This supports involvement in that epithelial model, not an exclusive absorption route or a measured contribution in the human intestine. Canonical proteins are SLC5A1/SGLT1 and SLC2A2/GLUT2. [Zou et al., 2014](https://pmc.ncbi.nlm.nih.gov/articles/PMC4210911/).

evidence_access

Full text retrieved; relevant methods/results/figure text reviewed. No independent raw-data verification.

experimental_model

Chemical classification, not an intervention or efficacy result.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

Glycosides remain separate from aglycones and from each other. This neutral identity record is navigation, not a signed causal mechanism.

plain_language

The anthocyanin class includes Cyanidin 3-O-beta-D-glucopyranoside; membership does not transfer experimental effects.

primary_references

Molecular Mechanisms Underlying the Absorption of Aglycone and Glycosidic Flavonoids in a Caco-2 BBe1 Cell Model. | 2020 | DOI 10.1021/acsomega.0c00379 | PMID 32455198 | https://pubmed.ncbi.nlm.nih.gov/32455198/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC7240828/ | https://doi.org/10.1021/acsomega.0c00379

source_locator

Reviewed reference lines 7-7; exact primary location described in quoted passage where extracted.

Anthocyanins: detailed mechanisms of action (reviewed 4 October 2026) · lines 7–7

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. · supports · Chemical classification, not an intervention or efficacy result. · source_derived_draft · unverified_draft

Anthocyanins are a class of glycosylated pigments, not one circulating drug. Their anthocyanidin cores include cyanidin, delphinidin, pelargonidin, peonidin, petunidin and malvidin. Sugar position, sugar identity, methylation and acylation change their behavior. Cyanidin, cyanidin-3-O-glucoside, cyanidin-3-O-galactoside and cyanidin-3,5-O-diglucoside are separate molecules. Nasunin is a distinct acylated delphinidin glycoside; it must not inherit every result obtained with cyanidin-3-glucoside. The tested aglycones and glycosides illustrate why the individual structures matter. [Purified-compound comparison](https://pmc.ncbi.nlm.nih.gov/articles/PMC7541926/).