Protocatechuic acid / 3,4-dihydroxybenzoic acid

evidence_access

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

experimental_contrast

{"intervention": "100 uM protocatechuic-acid", "comparator": "Untreated/vehicle-matched adipocytes in the corresponding assay", "endpoint": "In human omental adipocytes, 100 uM protocatechuic-acid 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, 100 uM protocatechuic-acid 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": "100 uM protocatechuic-acid", "comparator": "Untreated/vehicle-matched adipocytes in the corresponding assay", "endpoint": "In human omental adipocytes, 100 uM protocatechuic-acid 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, 100 uM protocatechuic-acid 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

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

experimental_contrast

{"intervention": "PCA exposure", "comparator": "Matched macrophage assay control; C3G comparator also reported", "endpoint": "PCA reduced macrophage miR-10b and increased ABCA1/ABCG1-related cholesterol efflux in the reported experimental program.", "effect_direction": "mixed", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.

experimental_model

Mixed mouse/human-derived macrophage program; exact species assignment of each PCA endpoint remains unextracted.

interpretation_status

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

limitations

Do not treat all listed homologs as simultaneously measured PCA targets in one species. Full paper required for species-separated PCA edges and exact concentrations.

plain_language

PCA reduced macrophage miR-10b and increased ABCA1/ABCG1-related cholesterol efflux in the reported experimental program.

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 · Mixed mouse/human-derived macrophage program; exact species assignment of each PCA endpoint remains unextracted. · 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/).

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

protocatechuic-acid 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_condition

protocatechuic-acid with functional mouse Pparg present · Protocatechuic acid / 3,4-dihydroxybenzoic acid Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_contrast

{"intervention": "protocatechuic-acid with mouse Pparg inhibition/silencing", "comparator": "protocatechuic-acid 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": "protocatechuic-acid", "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/).

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_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/).