Human Nrf2 / NFE2L2

evidence_span

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experimental_model

Copper and iron exposure with transcription-factor knockdown

exposure

CuCl2 or FeCl2 exposure; NFE2L2 or ATOX1 knockdown

limitations

One cancer-cell model. Expression changes do not prove increased glutathione synthesis, tumor progression, or a clinical nutrient interaction.

nutrient_topic

Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper

organism

Human MDA-MB-231 breast cancer cells

plain_language

The stress-response regulator was part of the transporter-expression response.

primary_references

[copper-p40944334] Copper induces cystine/glutamate antiporter SLC7A11 through the activation of Nrf2 and Atox1 pathways. (2025). https://pubmed.ncbi.nlm.nih.gov/40944334/ DOI: 10.1080/10715762.2025.2560847

tissue_or_cell_type

Cellular amino-acid transport machinery

Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1300–1311

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Copper and iron exposure with transcription-factor knockdown · source_derived_draft · unverified_draft

### copper-nrf2-slc7a11 NRF2 knockdown suppressed copper-induced SLC7A11 expression. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The stress-response regulator was part of the transporter-expression response. organism: Human MDA-MB-231 breast cancer cells tissue_or_cell_type: Cellular amino-acid transport machinery experimental_model: Copper and iron exposure with transcription-factor knockdown limitations: One cancer-cell model. Expression changes do not prove increased glutathione synthesis, tumor progression, or a clinical nutrient interaction. exposure: CuCl2 or FeCl2 exposure; NFE2L2 or ATOX1 knockdown evidence_span: {"source_cache": "artifacts/copper-research/40944334.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6df1716e8998546d22a1d96116e1bc35b1f7e24c94868ec5e441ada6a2be3e89", "start_char": 0, "end_char": 1634, "text_sha256": "6df1716e8998546d22a1d96116e1bc35b1f7e24c94868ec5e441ada6a2be3e89"} [copper-p40944334] Copper induces cystine/glutamate antiporter SLC7A11 through the activation of Nrf2 and Atox1 pathways. (2025). https://pubmed.ncbi.nlm.nih.gov/40944334/ DOI: 10.1080/10715762.2025.2560847

availability_state

machinery_impairment Imported condition classification; unverified.

duration

Not stated here

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Human gingival fibroblasts (HGF-1)

exposure

Nattokinase with Nrf2 or HO-1 inhibitors

limitations

A necessity test under a blocked pathway. Pharmacological inhibitors carry off-target risk that a genetic control would not, and no inactivated-enzyme arm was run.

organism

Human gingival fibroblasts (HGF-1)

plain_language

Inhibition of Nrf2 or of heme oxygenase 1 abolished the protective effect of nattokinase on COX-2, prostaglandin E2 and MMP-1 induction.

primary_references

Nuclear factor erythroid 2-related factor 2/heme oxygenase-1 activation by nattokinase reduces pro-inflammatory and matrix-degrading mediators in human gingival fibroblasts. (2026) https://pubmed.ncbi.nlm.nih.gov/41585176/ DOI: 10.1016/j.jds.2025.10.022

route

In vitro

tissue

Cell culture with pharmacological pathway inhibition

trigger_kind

machinery_impairment Imported condition classification; unverified.

Nattokinase: what the purified enzyme cleaves, what survives being eaten, and the gap between the two (2026-09-23) · lines 565–565

Original AI-assisted curation built from a supplied entity-first document of 105 entities and 129 claims. Every reference in that document was resolved against live PubMed with its abstract read and its DOI cross-checked on 2026-09-23, and the EFSA novel-food opinion was retrieved and read in full. That check corrected two PMIDs that pointed at unrelated papers, two DOIs, and two papers recorded as carrying no erratum that do carry one; it also reversed three findings the supplied document had stated backwards. Two papers carry a published correction, recorded as such and not as a retraction. Three sources are not indexed in PubMed and are cited by what they have. Laboratory lineages are recorded, so the four papers from one group, the three from another and the two readings of a single applicant dossier cannot be counted as separate lines of support. Study-specific doses, units, populations and limitations retained; activity units are never converted between systems. Not publisher full text. · supports · Human gingival fibroblasts (HGF-1) · source_derived_draft · unverified_draft

Inhibition of Nrf2 or of heme oxygenase 1 abolished the protective effect of nattokinase on COX-2, prostaglandin E2 and MMP-1 induction.

evidence_access

Primary full text

experimental_model

Human prostate cancer combination-treatment model.

limitations

NRF2/HMOX1 direction depends on cell state and iron handling; no universal ferroptosis prediction.

nutrient_topic

Spermidine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Spermidine

plain_language

Heme breakdown links this response to iron availability.

primary_references

Spermidine inactivates proteasome activity and enhances ferroptosis in prostate cancer. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40486852/ · DOI 10.1016/j.apsb.2025.02.023

Spermidine: biosynthesis, hypusination, transport and cross-nutrient mechanisms (2026-09-19) · lines 526–532

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human prostate cancer combination-treatment model. · source_derived_draft · unverified_draft

## spermidine-hmox1-iron Heme breakdown links this response to iron availability. The study linked elevated NRF2 to HMOX1 upregulation and increased labile ferrous iron during combination treatment. Model: Human prostate cancer combination-treatment model. Limitations: NRF2/HMOX1 direction depends on cell state and iron handling; no universal ferroptosis prediction. Evidence access: Primary full text Spermidine inactivates proteasome activity and enhances ferroptosis in prostate cancer. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40486852/ · DOI 10.1016/j.apsb.2025.02.023

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human endothelial-cell Nrf2 knockdown.

limitations

Partial suppression does not identify all upstream sensors or show that more astaxanthin can replace Nrf2.

nutrient_topic

Astaxanthin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Astaxanthin

plain_language

The response was weaker when its transcriptional machinery was reduced.

primary_references

Astaxanthin Induces the Nrf2/HO-1 Antioxidant Pathway in Human Umbilical Vein Endothelial Cells by Generating Trace Amounts of ROS. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29381356/ · DOI 10.1021/acs.jafc.7b05493

trigger_kind

machinery_impairment Imported condition classification; unverified.

Astaxanthin: transport, membrane chemistry, signaling and nutrient interactions (2026-09-19) · lines 230–236

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human endothelial-cell Nrf2 knockdown. · source_derived_draft · unverified_draft

## astaxanthin-nrf2-loss The response was weaker when its transcriptional machinery was reduced. Nrf2 siRNA reduced astaxanthin-induced HO-1 expression by about 60% in HUVECs. Model: Human endothelial-cell Nrf2 knockdown. Limitations: Partial suppression does not identify all upstream sensors or show that more astaxanthin can replace Nrf2. Evidence access: Primary abstract Astaxanthin Induces the Nrf2/HO-1 Antioxidant Pathway in Human Umbilical Vein Endothelial Cells by Generating Trace Amounts of ROS. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29381356/ · DOI 10.1021/acs.jafc.7b05493

evidence_span

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experimental_model

Cell perturbation and xenograft experiments

exposure

DIM; NRF2 overexpression and pharmacological rescue controls

limitations

Preclinical cancer context. Reduced defense here differs from Nrf2 induction in fibroblasts; neither result proves a universal antioxidant or prooxidant effect in people.

nutrient_topic

Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM

organism

Human non-small-cell lung-cancer cells and mouse xenografts

plain_language

A particular tumor context showed suppression of this defense/signaling component.

primary_references

[dim-p40100489] 3,3'-diindolylmethane induces ferroptosis and inhibits proliferation in non-small-cell lung cancer through the AHR/NRF2/GPX4 axis. (2025). https://pubmed.ncbi.nlm.nih.gov/40100489/ DOI: 10.1007/s12672-025-02096-z

tissue_or_cell_type

Ferroptosis and AHR/NRF2/GPX4

Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1299–1310

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell perturbation and xenograft experiments · source_derived_draft · unverified_draft

### dim-nsclc-nfe2l2 DIM treatment reduced NRF2 in the tested lung-cancer models. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A particular tumor context showed suppression of this defense/signaling component. organism: Human non-small-cell lung-cancer cells and mouse xenografts tissue_or_cell_type: Ferroptosis and AHR/NRF2/GPX4 experimental_model: Cell perturbation and xenograft experiments limitations: Preclinical cancer context. Reduced defense here differs from Nrf2 induction in fibroblasts; neither result proves a universal antioxidant or prooxidant effect in people. exposure: DIM; NRF2 overexpression and pharmacological rescue controls evidence_span: {"source_cache": "artifacts/dim-research/40100489.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0", "start_char": 0, "end_char": 1722, "text_sha256": "99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0"} [dim-p40100489] 3,3'-diindolylmethane induces ferroptosis and inhibits proliferation in non-small-cell lung cancer through the AHR/NRF2/GPX4 axis. (2025). https://pubmed.ncbi.nlm.nih.gov/40100489/ DOI: 10.1007/s12672-025-02096-z

evidence_access

Primary abstract

experimental_model

Human colorectal cell culture and bisulfite sequencing.

limitations

Different model; not a proven contradiction or universal epigenetic reset.

nutrient_topic

Luteolin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Luteolin / 3′,4′,5,7-tetrahydroxyflavone

plain_language

The direction differs from the mouse-liver result.

primary_references

The dietary flavone luteolin epigenetically activates the Nrf2 pathway and blocks cell transformation in human colorectal cancer HCT116 cells. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30129150/ · DOI 10.1002/jcb.27275

Luteolin: metabolism, immune signaling, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 468–474

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human colorectal cell culture and bisulfite sequencing. · source_derived_draft · unverified_draft

## luteolin-human-nrf2-up The direction differs from the mouse-liver result. Luteolin reduced NFE2L2-promoter methylation and increased Nrf2 expression in human HCT116 colorectal cells. Model: Human colorectal cell culture and bisulfite sequencing. Limitations: Different model; not a proven contradiction or universal epigenetic reset. Evidence access: Primary abstract The dietary flavone luteolin epigenetically activates the Nrf2 pathway and blocks cell transformation in human colorectal cancer HCT116 cells. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30129150/ · DOI 10.1002/jcb.27275

duration

Not stated here

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Human gingival fibroblasts (HGF-1)

exposure

Nattokinase pretreatment

limitations

A cell model of periodontal inflammation, not a vascular one. The proximal target by which an extracellular protease reaches Nrf2 is not established.

organism

Human gingival fibroblasts (HGF-1)

plain_language

Nattokinase pretreatment enhanced Nrf2 activation in particulate-matter-exposed human gingival fibroblasts, confirmed by antioxidant-response-element luciferase assay.

primary_references

Nuclear factor erythroid 2-related factor 2/heme oxygenase-1 activation by nattokinase reduces pro-inflammatory and matrix-degrading mediators in human gingival fibroblasts. (2026) https://pubmed.ncbi.nlm.nih.gov/41585176/ DOI: 10.1016/j.jds.2025.10.022

route

In vitro

tissue

Cell culture, particulate-matter exposure

Nattokinase: what the purified enzyme cleaves, what survives being eaten, and the gap between the two (2026-09-23) · lines 543–543

Original AI-assisted curation built from a supplied entity-first document of 105 entities and 129 claims. Every reference in that document was resolved against live PubMed with its abstract read and its DOI cross-checked on 2026-09-23, and the EFSA novel-food opinion was retrieved and read in full. That check corrected two PMIDs that pointed at unrelated papers, two DOIs, and two papers recorded as carrying no erratum that do carry one; it also reversed three findings the supplied document had stated backwards. Two papers carry a published correction, recorded as such and not as a retraction. Three sources are not indexed in PubMed and are cited by what they have. Laboratory lineages are recorded, so the four papers from one group, the three from another and the two readings of a single applicant dossier cannot be counted as separate lines of support. Study-specific doses, units, populations and limitations retained; activity units are never converted between systems. Not publisher full text. · supports · Human gingival fibroblasts (HGF-1) · source_derived_draft · unverified_draft

Nattokinase pretreatment enhanced Nrf2 activation in particulate-matter-exposed human gingival fibroblasts, confirmed by antioxidant-response-element luciferase assay.

evidence_span

{"source_cache": "artifacts/sulforaphane-research/15572695.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d120b0ea48a77a99b12e9147e4acb02fd63026ed729a37d5e2edf174c5674765", "start_char": 0, "end_char": 1484, "text_sha256": "d120b0ea48a77a99b12e9147e4acb02fd63026ed729a37d5e2edf174c5674765"}

experimental_model

Cell transfection, coimmunoprecipitation and ubiquitination assays

exposure

Sulforaphane or quinone stress; C151S KEAP1 comparison

limitations

The measured interaction is ubiquitin-ligase regulation; do not describe it as obligatory physical release of all bound Nrf2.

nutrient_topic

Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study

organism

Human protein constructs in mammalian cell systems

plain_language

Nrf2 is normally marked for turnover.

primary_references

[sulforaphane-p15572695] Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex. (2004). https://pubmed.ncbi.nlm.nih.gov/15572695/ DOI: 10.1128/mcb.24.24.10941-10953.2004

tissue_or_cell_type

KEAP1-CUL3-RBX1 control of Nrf2

Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 463–474

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell transfection, coimmunoprecipitation and ubiquitination assays · source_derived_draft · unverified_draft

### sulforaphane-ligase-nrf2 The KEAP1-CUL3-RBX1 complex targeted multiple lysines in the Nrf2 Neh2 domain for ubiquitination. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: Nrf2 is normally marked for turnover. organism: Human protein constructs in mammalian cell systems tissue_or_cell_type: KEAP1-CUL3-RBX1 control of Nrf2 experimental_model: Cell transfection, coimmunoprecipitation and ubiquitination assays limitations: The measured interaction is ubiquitin-ligase regulation; do not describe it as obligatory physical release of all bound Nrf2. exposure: Sulforaphane or quinone stress; C151S KEAP1 comparison evidence_span: {"source_cache": "artifacts/sulforaphane-research/15572695.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d120b0ea48a77a99b12e9147e4acb02fd63026ed729a37d5e2edf174c5674765", "start_char": 0, "end_char": 1484, "text_sha256": "d120b0ea48a77a99b12e9147e4acb02fd63026ed729a37d5e2edf174c5674765"} [sulforaphane-p15572695] Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex. (2004). https://pubmed.ncbi.nlm.nih.gov/15572695/ DOI: 10.1128/mcb.24.24.10941-10953.2004

evidence_span

{"source_cache": "artifacts/hbot-research/31035003.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e0b19a857412f1a255ecc82052eb403389bcf5596a562828c04558e1d4354efc", "start_char": 0, "end_char": 1966, "text_sha256": "e0b19a857412f1a255ecc82052eb403389bcf5596a562828c04558e1d4354efc"}

experimental_model

Randomised comparison of 32 patients receiving standard wound care with or without hyperbaric oxygen, with ulcer tissue biopsies

exposure

Hyperbaric oxygen with standard wound care for 20 days

limitations

A small randomised human study with tissue-level molecular endpoints. Correlations between Nrf2 and growth factors are associations within treated tissue.

nutrient_topic

Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

organism

Human

plain_language

The master switch for antioxidant defence is measurably higher in the treated wound.

primary_references

[hbot-p31035003] Tissue-specific role of Nrf2 in the treatment of diabetic foot ulcers during hyperbaric oxygen therapy. (2019). https://pubmed.ncbi.nlm.nih.gov/31035003/ DOI: 10.1016/j.freeradbiomed.2019.04.031

tissue_or_cell_type

Diabetic foot ulcer tissue

Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 816–827

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomised comparison of 32 patients receiving standard wound care with or without hyperbaric oxygen, with ulcer tissue biopsies · source_derived_draft · unverified_draft

### hbot-nrf2-induction Tissue levels of Nrf2 and its downstream targets were significantly increased in patients receiving hyperbaric oxygen compared with standard therapy alone. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The master switch for antioxidant defence is measurably higher in the treated wound. organism: Human tissue_or_cell_type: Diabetic foot ulcer tissue experimental_model: Randomised comparison of 32 patients receiving standard wound care with or without hyperbaric oxygen, with ulcer tissue biopsies limitations: A small randomised human study with tissue-level molecular endpoints. Correlations between Nrf2 and growth factors are associations within treated tissue. exposure: Hyperbaric oxygen with standard wound care for 20 days evidence_span: {"source_cache": "artifacts/hbot-research/31035003.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e0b19a857412f1a255ecc82052eb403389bcf5596a562828c04558e1d4354efc", "start_char": 0, "end_char": 1966, "text_sha256": "e0b19a857412f1a255ecc82052eb403389bcf5596a562828c04558e1d4354efc"} [hbot-p31035003] Tissue-specific role of Nrf2 in the treatment of diabetic foot ulcers during hyperbaric oxygen therapy. (2019). https://pubmed.ncbi.nlm.nih.gov/31035003/ DOI: 10.1016/j.freeradbiomed.2019.04.031

evidence_span

{"source_cache": "artifacts/berberine-research/29891588.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e59ba2b3b6e505cf3b220d32040e37f53553ea73427dd522cf7ea237d7d0f405", "start_char": 0, "end_char": 1752, "text_sha256": "e59ba2b3b6e505cf3b220d32040e37f53553ea73427dd522cf7ea237d7d0f405"}

experimental_model

Nrf2 reporter, gene silencing and expression assays

exposure

Berberine concentration and time response

limitations

Transporter expression after prolonged exposure is not the same endpoint as acute competitive inhibition. Rat colitis improvement does not establish human IBD efficacy.

nutrient_topic

Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine

organism

Human Caco-2 cells; rat colitis in a separate arm

plain_language

An exposure can turn on a transcriptional response linked to an efflux pump.

primary_references

[berberine-p29891588] Berberine Upregulates P-Glycoprotein in Human Caco-2 Cells and in an Experimental Model of Colitis in the Rat via Activation of Nrf2-Dependent Mechanisms. (2018). https://pubmed.ncbi.nlm.nih.gov/29891588/ DOI: 10.1124/jpet.118.249615

tissue_or_cell_type

Nrf2-dependent ABCB1 expression

Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 532–543

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Nrf2 reporter, gene silencing and expression assays · source_derived_draft · unverified_draft

### berberine-nrf2-reporter Berberine increased Nrf2 reporter activity in Caco-2 cells. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: An exposure can turn on a transcriptional response linked to an efflux pump. organism: Human Caco-2 cells; rat colitis in a separate arm tissue_or_cell_type: Nrf2-dependent ABCB1 expression experimental_model: Nrf2 reporter, gene silencing and expression assays limitations: Transporter expression after prolonged exposure is not the same endpoint as acute competitive inhibition. Rat colitis improvement does not establish human IBD efficacy. exposure: Berberine concentration and time response evidence_span: {"source_cache": "artifacts/berberine-research/29891588.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e59ba2b3b6e505cf3b220d32040e37f53553ea73427dd522cf7ea237d7d0f405", "start_char": 0, "end_char": 1752, "text_sha256": "e59ba2b3b6e505cf3b220d32040e37f53553ea73427dd522cf7ea237d7d0f405"} [berberine-p29891588] Berberine Upregulates P-Glycoprotein in Human Caco-2 Cells and in an Experimental Model of Colitis in the Rat via Activation of Nrf2-Dependent Mechanisms. (2018). https://pubmed.ncbi.nlm.nih.gov/29891588/ DOI: 10.1124/jpet.118.249615

evidence_access

Primary full text

experimental_model

Human PC3/DU145 cells and hypusination perturbation.

limitations

Assay-specific pathway interpretation; does not mean NRF2 is always protective.

nutrient_topic

Spermidine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Spermidine

plain_language

A translation response can raise a stress regulator.

primary_references

Spermidine inactivates proteasome activity and enhances ferroptosis in prostate cancer. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40486852/ · DOI 10.1016/j.apsb.2025.02.023

Spermidine: biosynthesis, hypusination, transport and cross-nutrient mechanisms (2026-09-19) · lines 510–516

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human PC3/DU145 cells and hypusination perturbation. · source_derived_draft · unverified_draft

## spermidine-nrf2-translation A translation response can raise a stress regulator. The prostate-cell study linked spermidine-driven eIF5A hypusination to increased NRF2 translation. Model: Human PC3/DU145 cells and hypusination perturbation. Limitations: Assay-specific pathway interpretation; does not mean NRF2 is always protective. Evidence access: Primary full text Spermidine inactivates proteasome activity and enhances ferroptosis in prostate cancer. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40486852/ · DOI 10.1016/j.apsb.2025.02.023

duration

Acute

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

RAW 264.7 murine macrophages

exposure

SB239063 with (+)-lariciresinol

limitations

Inhibitor dependence establishes that p38 is required, not that lariciresinol binds or acts on p38 directly.

organism

RAW 264.7 murine macrophages

plain_language

The p38 inhibitor SB239063 suppressed the (+)-lariciresinol-induced response, placing p38 upstream of it.

primary_references

Antioxidant efficacy and the upregulation of Nrf2-mediated HO-1 expression by (+)-lariciresinol, a lignan isolated from Rubia philippinensis, through the activation of p38. (2017). https://pubmed.ncbi.nlm.nih.gov/28378774/ DOI: 10.1038/srep46035

route

In vitro

tissue

p38 dependence of the antioxidant response

Lariciresinol: five molecules under one name, and the mechanisms each one carries (2026-09-22) · lines 22–31

Original AI-assisted curation of twelve primary studies, every abstract read and all DOIs cross-checked against live PubMed metadata. Mechanism edges only, with no conclusion or claim of benefit recorded. Three author clusters account for eight of the twelve and carry shared laboratory keys. Study-specific concentrations, negative findings and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

## p38-required-for-the-nrf2-response The p38 inhibitor SB239063 suppressed the (+)-lariciresinol-induced response, placing p38 upstream of it. Model/species: RAW 264.7 murine macrophages Tissue/system: p38 dependence of the antioxidant response Exposure: SB239063 with (+)-lariciresinol Route: In vitro Duration: Acute Limits: Inhibitor dependence establishes that p38 is required, not that lariciresinol binds or acts on p38 directly. Primary reference: Antioxidant efficacy and the upregulation of Nrf2-mediated HO-1 expression by (+)-lariciresinol, a lignan isolated from Rubia philippinensis, through the activation of p38. (2017). https://pubmed.ncbi.nlm.nih.gov/28378774/ DOI: 10.1038/srep46035 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

duration

Not stated here

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

RAW 264.7 murine macrophages

exposure

(+)-Lariciresinol, dose-dependent, without cytotoxicity

limitations

Measured as transcript and protein level rather than as nuclear translocation in the abstract.

organism

RAW 264.7 murine macrophages

plain_language

(+)-Lariciresinol increased Nrf2 at both transcriptional and translational levels.

primary_references

Antioxidant efficacy and the upregulation of Nrf2-mediated HO-1 expression by (+)-lariciresinol, a lignan isolated from Rubia philippinensis, through the activation of p38. (2017). https://pubmed.ncbi.nlm.nih.gov/28378774/ DOI: 10.1038/srep46035

route

In vitro

tissue

Nrf2 transcription factor abundance

Lariciresinol: five molecules under one name, and the mechanisms each one carries (2026-09-22) · lines 33–42

Original AI-assisted curation of twelve primary studies, every abstract read and all DOIs cross-checked against live PubMed metadata. Mechanism edges only, with no conclusion or claim of benefit recorded. Three author clusters account for eight of the twelve and carry shared laboratory keys. Study-specific concentrations, negative findings and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

## plus-lariciresinol-raises-nrf2 (+)-Lariciresinol increased Nrf2 at both transcriptional and translational levels. Model/species: RAW 264.7 murine macrophages Tissue/system: Nrf2 transcription factor abundance Exposure: (+)-Lariciresinol, dose-dependent, without cytotoxicity Route: In vitro Duration: Not stated here Limits: Measured as transcript and protein level rather than as nuclear translocation in the abstract. Primary reference: Antioxidant efficacy and the upregulation of Nrf2-mediated HO-1 expression by (+)-lariciresinol, a lignan isolated from Rubia philippinensis, through the activation of p38. (2017). https://pubmed.ncbi.nlm.nih.gov/28378774/ DOI: 10.1038/srep46035 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

dose

Betanin 2, 10 and 20 micromolar

duration

Not specified in accessed primary abstract

evidence_access

Primary PubMed abstract; detailed exposure for PMID 23931157 additionally checked in publisher results. No uninspected full text is claimed.

evidence_scope

literature_reviewed; source-derived curation, not universally established human effects

experimental_model

Human THLE-2 non-tumour liver and HepG2 hepatoma cell lines

limitations

Responses differed by cell line. Nuclear translocation is not proof of universal transcriptional activation; kinase association does not prove direct binding. Same-study cell-context difference, not a scientific contradiction.

nutrient_topic

Betalains collection; each molecular form, species, exposure and preparation remains explicit. · Betalains

organism

Human THLE-2 non-tumour liver and HepG2 hepatoma cell lines

plain_language

Betanin increased Nrf2 binding to antioxidant response elements in THLE-2 cells; this response was absent in HepG2 cells.

primary_references

Betanin, a beetroot component, induces nuclear factor erythroid-2-related factor 2-mediated expression of detoxifying/antioxidant enzymes in human liver cell lines. (2013). https://pubmed.ncbi.nlm.nih.gov/23769299/ DOI: 10.1017/S0007114513001645

route

In vitro incubation

tissue

Liver-derived cells; cytosol and nucleus

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 217–225

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Human THLE-2 non-tumour liver and HepG2 hepatoma cell lines · source_derived_draft · unverified_draft

## betalains-nrf2-are Betanin increased Nrf2 binding to antioxidant response elements in THLE-2 cells; this response was absent in HepG2 cells. Model/species: Human THLE-2 non-tumour liver and HepG2 hepatoma cell lines Tissue: Liver-derived cells; cytosol and nucleus Exposure: Betanin 2, 10 and 20 micromolar Route: In vitro incubation Duration: Not specified in accessed primary abstract Limits: Responses differed by cell line. Nuclear translocation is not proof of universal transcriptional activation; kinase association does not prove direct binding. Same-study cell-context difference, not a scientific contradiction. Primary reference: Betanin, a beetroot component, induces nuclear factor erythroid-2-related factor 2-mediated expression of detoxifying/antioxidant enzymes in human liver cell lines. (2013). https://pubmed.ncbi.nlm.nih.gov/23769299/ DOI: 10.1017/S0007114513001645

dose

Betanin 2, 10 and 20 micromolar

duration

Not specified in accessed primary abstract

evidence_access

Primary PubMed abstract; detailed exposure for PMID 23931157 additionally checked in publisher results. No uninspected full text is claimed.

evidence_scope

literature_reviewed; source-derived curation, not universally established human effects

experimental_model

Human THLE-2 non-tumour liver and HepG2 hepatoma cell lines

limitations

Responses differed by cell line. Nuclear translocation is not proof of universal transcriptional activation; kinase association does not prove direct binding.

nutrient_topic

Betalains collection; each molecular form, species, exposure and preparation remains explicit. · Betalains

organism

Human THLE-2 non-tumour liver and HepG2 hepatoma cell lines

plain_language

Betanin promoted nuclear redistribution of Nrf2 in both THLE-2 and HepG2 cells.

primary_references

Betanin, a beetroot component, induces nuclear factor erythroid-2-related factor 2-mediated expression of detoxifying/antioxidant enzymes in human liver cell lines. (2013). https://pubmed.ncbi.nlm.nih.gov/23769299/ DOI: 10.1017/S0007114513001645

route

In vitro incubation

tissue

Liver-derived cells; cytosol and nucleus

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 207–215

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Human THLE-2 non-tumour liver and HepG2 hepatoma cell lines · source_derived_draft · unverified_draft

## betalains-nrf2-translocation Betanin promoted nuclear redistribution of Nrf2 in both THLE-2 and HepG2 cells. Model/species: Human THLE-2 non-tumour liver and HepG2 hepatoma cell lines Tissue: Liver-derived cells; cytosol and nucleus Exposure: Betanin 2, 10 and 20 micromolar Route: In vitro incubation Duration: Not specified in accessed primary abstract Limits: Responses differed by cell line. Nuclear translocation is not proof of universal transcriptional activation; kinase association does not prove direct binding. Primary reference: Betanin, a beetroot component, induces nuclear factor erythroid-2-related factor 2-mediated expression of detoxifying/antioxidant enzymes in human liver cell lines. (2013). https://pubmed.ncbi.nlm.nih.gov/23769299/ DOI: 10.1017/S0007114513001645

acting_entity

s-allylcysteine

dose

Not specified in accessed abstract

duration

Not specified in accessed abstract

evidence_access

Primary abstract

experimental_comparison

SAC with PhIP challenge and corresponding cell controls

experimental_model

Normal human colonic mucosal epithelial cells exposed to PhIP

interpretation_status

Source-derived research curation; not independent primary verification

limitations

The abstract proposes altered KEAP1 association and kinase signaling; causal order is not fully resolved.

nutrient_topic

S-allylcysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · S-allyl-L-cysteine / SAC

organism

Homo sapiens

plain_language

Defense signaling accompanied protection in this cell model.

primary_references

[35753083] S-Allylcysteine Potently Protects against PhIP-Induced DNA Damage via Nrf2/AhR Signaling Pathway Modulation in Normal Human Colonic Mucosal Epithelial Cells. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35753083/ · DOI 10.1002/mnfr.202101141

route

Cell culture

tissue_or_cell_type

Normal human colonic mucosal epithelial cells exposed to PhIP

S-allylcysteine: sulfur signaling, redox responses and cross-nutrient mechanisms (2026-09-20) · lines 158–165

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Normal human colonic mucosal epithelial cells exposed to PhIP · source_derived_draft · unverified_draft

## s-allylcysteine-colon-nrf2 Defense signaling accompanied protection in this cell model. SAC treatment induced Nrf2/HO-1 signaling during PhIP challenge in human colonic epithelial cells. Model: Normal human colonic mucosal epithelial cells exposed to PhIP Limitations: The abstract proposes altered KEAP1 association and kinase signaling; causal order is not fully resolved. Evidence access: Primary abstract [35753083] S-Allylcysteine Potently Protects against PhIP-Induced DNA Damage via Nrf2/AhR Signaling Pathway Modulation in Normal Human Colonic Mucosal Epithelial Cells. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35753083/ · DOI 10.1002/mnfr.202101141 Structured context: {"organism": "Homo sapiens", "tissue_or_cell_type": "Normal human colonic mucosal epithelial cells exposed to PhIP", "dose": "Not specified in accessed abstract", "duration": "Not specified in accessed abstract", "route": "Cell culture", "experimental_comparison": "SAC with PhIP challenge and corresponding cell controls", "acting_entity": "s-allylcysteine", "interpretation_status": "Source-derived research curation; not independent primary verification"}

acting_entity

s-allylcysteine

dose

10 or 20 mM SAC; mechanistic endpoints 20 mM

duration

24, 48 or 72 hours; mechanistic endpoints 72 hours

evidence_access

Primary abstract

experimental_comparison

SAC; BEAS-2B and A549 comparator cell lines also studied

experimental_model

HCC827 and NCI-H1975 lung cancer cells

interpretation_status

Source-derived research curation; not independent primary verification

limitations

Very high concentration in malignant cells; not a contradiction of lower-exposure or different-tissue observations.

nutrient_topic

S-allylcysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · S-allyl-L-cysteine / SAC

organism

Homo sapiens

plain_language

A different model showed the opposite Nrf2 response.

primary_references

[33136700] S-allylcysteine induces cytotoxic effects in two human lung cancer cell lines via induction of oxidative damage, downregulation of Nrf2 and NF-κB, and apoptosis. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33136700/ · DOI 10.1097/CAD.0000000000001015

route

Cell culture

tissue_or_cell_type

HCC827 and NCI-H1975 lung cancer cells

S-allylcysteine: sulfur signaling, redox responses and cross-nutrient mechanisms (2026-09-20) · lines 311–318

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · HCC827 and NCI-H1975 lung cancer cells · source_derived_draft · unverified_draft

## s-allylcysteine-lung-nrf2 A different model showed the opposite Nrf2 response. SAC at 20 mM for 72 hours reduced Nrf2 protein in HCC827 and NCI-H1975 lung cancer cells. Model: HCC827 and NCI-H1975 lung cancer cells Limitations: Very high concentration in malignant cells; not a contradiction of lower-exposure or different-tissue observations. Evidence access: Primary abstract [33136700] S-allylcysteine induces cytotoxic effects in two human lung cancer cell lines via induction of oxidative damage, downregulation of Nrf2 and NF-κB, and apoptosis. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33136700/ · DOI 10.1097/CAD.0000000000001015 Structured context: {"organism": "Homo sapiens", "tissue_or_cell_type": "HCC827 and NCI-H1975 lung cancer cells", "dose": "10 or 20 mM SAC; mechanistic endpoints 20 mM", "duration": "24, 48 or 72 hours; mechanistic endpoints 72 hours", "route": "Cell culture", "experimental_comparison": "SAC; BEAS-2B and A549 comparator cell lines also studied", "acting_entity": "s-allylcysteine", "interpretation_status": "Source-derived research curation; not independent primary verification"}

evidence_span

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experimental_model

Copper and iron exposure with transcription-factor knockdown

exposure

CuCl2 or FeCl2 exposure; NFE2L2 or ATOX1 knockdown

limitations

One cancer-cell model. Expression changes do not prove increased glutathione synthesis, tumor progression, or a clinical nutrient interaction.

nutrient_topic

Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper

organism

Human MDA-MB-231 breast cancer cells

plain_language

A stress-response regulator moved to the cell’s DNA-containing compartment.

primary_references

[copper-p40944334] Copper induces cystine/glutamate antiporter SLC7A11 through the activation of Nrf2 and Atox1 pathways. (2025). https://pubmed.ncbi.nlm.nih.gov/40944334/ DOI: 10.1080/10715762.2025.2560847

tissue_or_cell_type

Cellular amino-acid transport machinery

Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1287–1298

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Copper and iron exposure with transcription-factor knockdown · source_derived_draft · unverified_draft

### copper-cu-nrf2 CuCl2 exposure promoted NRF2 nuclear translocation in the tested cancer cells. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: A stress-response regulator moved to the cell’s DNA-containing compartment. organism: Human MDA-MB-231 breast cancer cells tissue_or_cell_type: Cellular amino-acid transport machinery experimental_model: Copper and iron exposure with transcription-factor knockdown limitations: One cancer-cell model. Expression changes do not prove increased glutathione synthesis, tumor progression, or a clinical nutrient interaction. exposure: CuCl2 or FeCl2 exposure; NFE2L2 or ATOX1 knockdown evidence_span: {"source_cache": "artifacts/copper-research/40944334.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6df1716e8998546d22a1d96116e1bc35b1f7e24c94868ec5e441ada6a2be3e89", "start_char": 0, "end_char": 1634, "text_sha256": "6df1716e8998546d22a1d96116e1bc35b1f7e24c94868ec5e441ada6a2be3e89"} [copper-p40944334] Copper induces cystine/glutamate antiporter SLC7A11 through the activation of Nrf2 and Atox1 pathways. (2025). https://pubmed.ncbi.nlm.nih.gov/40944334/ DOI: 10.1080/10715762.2025.2560847

availability_state

machinery_impairment Imported condition classification; unverified.

dose

ME-D with brusatol

duration

Acute

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human BEAS-2B cells

limitations

Brusatol is a pharmacological perturbation with effects beyond a nutritional setting; the experiment supports pathway dependence for NQO1, not every effect of Moringa.

nutrient_topic

Moringa oleifera chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Moringa oleifera

organism

Human BEAS-2B cells

plain_language

Brusatol treatment significantly diminished the ME-D-induced increase in NQO1 expression in BEAS-2B cells, supporting NRF2 dependence for that measured response.

primary_references

Development of Moringa oleifera as functional food targeting NRF2 signaling: antioxidant and anti-inflammatory activity in experimental model systems. (2023). https://pubmed.ncbi.nlm.nih.gov/37114361/ DOI: 10.1039/d3fo00572k

route

In vitro perturbation

tissue

Pharmacological NRF2 perturbation

trigger_kind

machinery_impairment Imported condition classification; unverified.

Moringa oleifera: mechanism of action and interactions (2026-09-20) · lines 79–88

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Human BEAS-2B cells · source_derived_draft · unverified_draft

## moringa-brusatol-blocks-nrf2-response Brusatol treatment significantly diminished the ME-D-induced increase in NQO1 expression in BEAS-2B cells, supporting NRF2 dependence for that measured response. Model/species: Human BEAS-2B cells Tissue/system: Pharmacological NRF2 perturbation Exposure: ME-D with brusatol Route: In vitro perturbation Duration: Acute Limits: Brusatol is a pharmacological perturbation with effects beyond a nutritional setting; the experiment supports pathway dependence for NQO1, not every effect of Moringa. Primary reference: Development of Moringa oleifera as functional food targeting NRF2 signaling: antioxidant and anti-inflammatory activity in experimental model systems. (2023). https://pubmed.ncbi.nlm.nih.gov/37114361/ DOI: 10.1039/d3fo00572k Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

dose

Chemically profiled ME-D hot-soup or freeze-dried preparation

duration

Acute cell exposure and study-specified mouse dosing

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human BEAS-2B cells and orally dosed mice

limitations

The preparation contained moringin, glucomoringin and polyphenols, so the response cannot be assigned to one constituent or treated as a human clinical outcome.

nutrient_topic

Moringa oleifera chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Moringa oleifera

organism

Human BEAS-2B cells and orally dosed mice

plain_language

The standardized multi-constituent ME-D leaf preparation increased NRF2-regulated NQO1 and HMOX1 expression and cellular glutathione in BEAS-2B cells, and increased NRF2-regulated genes after oral dosing in mice.

primary_references

Development of Moringa oleifera as functional food targeting NRF2 signaling: antioxidant and anti-inflammatory activity in experimental model systems. (2023). https://pubmed.ncbi.nlm.nih.gov/37114361/ DOI: 10.1039/d3fo00572k

route

In vitro and oral mouse exposure

tissue

NRF2-linked gene and glutathione responses

Moringa oleifera: mechanism of action and interactions (2026-09-20) · lines 68–77

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Human BEAS-2B cells and orally dosed mice · source_derived_draft · unverified_draft

## moringa-standardized-preparation-nrf2 The standardized multi-constituent ME-D leaf preparation increased NRF2-regulated NQO1 and HMOX1 expression and cellular glutathione in BEAS-2B cells, and increased NRF2-regulated genes after oral dosing in mice. Model/species: Human BEAS-2B cells and orally dosed mice Tissue/system: NRF2-linked gene and glutathione responses Exposure: Chemically profiled ME-D hot-soup or freeze-dried preparation Route: In vitro and oral mouse exposure Duration: Acute cell exposure and study-specified mouse dosing Limits: The preparation contained moringin, glucomoringin and polyphenols, so the response cannot be assigned to one constituent or treated as a human clinical outcome. Primary reference: Development of Moringa oleifera as functional food targeting NRF2 signaling: antioxidant and anti-inflammatory activity in experimental model systems. (2023). https://pubmed.ncbi.nlm.nih.gov/37114361/ DOI: 10.1039/d3fo00572k Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_span

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experimental_model

Cell perturbation and xenograft experiments

exposure

DIM; NRF2 overexpression and pharmacological rescue controls

limitations

Preclinical cancer context. Reduced defense here differs from Nrf2 induction in fibroblasts; neither result proves a universal antioxidant or prooxidant effect in people.

nutrient_topic

Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM

organism

Human non-small-cell lung-cancer cells and mouse xenografts

plain_language

Perturbation controls helped connect the response to specific defenses.

primary_references

[dim-p40100489] 3,3'-diindolylmethane induces ferroptosis and inhibits proliferation in non-small-cell lung cancer through the AHR/NRF2/GPX4 axis. (2025). https://pubmed.ncbi.nlm.nih.gov/40100489/ DOI: 10.1007/s12672-025-02096-z

tissue_or_cell_type

Ferroptosis and AHR/NRF2/GPX4

Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1351–1362

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell perturbation and xenograft experiments · source_derived_draft · unverified_draft

### dim-nsclc-ferroptosis DIM induced ferroptosis that could be reversed by ferrostatin-1, NAC or the tested AHR antagonist; NRF2 overexpression also reversed it. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Perturbation controls helped connect the response to specific defenses. organism: Human non-small-cell lung-cancer cells and mouse xenografts tissue_or_cell_type: Ferroptosis and AHR/NRF2/GPX4 experimental_model: Cell perturbation and xenograft experiments limitations: Preclinical cancer context. Reduced defense here differs from Nrf2 induction in fibroblasts; neither result proves a universal antioxidant or prooxidant effect in people. exposure: DIM; NRF2 overexpression and pharmacological rescue controls evidence_span: {"source_cache": "artifacts/dim-research/40100489.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0", "start_char": 0, "end_char": 1722, "text_sha256": "99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0"} [dim-p40100489] 3,3'-diindolylmethane induces ferroptosis and inhibits proliferation in non-small-cell lung cancer through the AHR/NRF2/GPX4 axis. (2025). https://pubmed.ncbi.nlm.nih.gov/40100489/ DOI: 10.1007/s12672-025-02096-z

evidence_access

Primary full text

experimental_model

Human cell ChIP; 10–60 micromolar studies.

limitations

Promoter association is not a direct luteolin–TET1 binding assay.

nutrient_topic

Luteolin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Luteolin / 3′,4′,5,7-tetrahydroxyflavone

plain_language

DNA-modifying machinery participates in the response.

primary_references

Luteolin promotes apoptotic cell death via upregulation of Nrf2 expression by DNA demethylase and the interaction of Nrf2 with p53 in human colon cancer cells. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30988303/ · DOI 10.1038/s12276-019-0238-y

Luteolin: metabolism, immune signaling, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 484–490

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human cell ChIP; 10–60 micromolar studies. · source_derived_draft · unverified_draft

## luteolin-tet1-recruitment DNA-modifying machinery participates in the response. Luteolin increased TET1 association with the NFE2L2 promoter in human colon cancer cells. Model: Human cell ChIP; 10–60 micromolar studies. Limitations: Promoter association is not a direct luteolin–TET1 binding assay. Evidence access: Primary full text Luteolin promotes apoptotic cell death via upregulation of Nrf2 expression by DNA demethylase and the interaction of Nrf2 with p53 in human colon cancer cells. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30988303/ · DOI 10.1038/s12276-019-0238-y

evidence_span

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experimental_model

HCT116 mechanism and AOM/DSS knockout-mouse experiment

exposure

Purified cinnamaldehyde cell exposure and dietary supplementation in mice

limitations

No human cancer-prevention outcome; the abstract identifies C151 dependence but does not resolve the transfected KEAP1 construct species.

nutrient_topic

Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect. · Ceylon cinnamon / Cinnamomum verum bark preparations

organism

Human HCT116 cells; KEAP1 construct species unresolved

plain_language

These cells accumulated more glutathione; that does not measure whole-body glutathione supply.

primary_references

[ceylon-p25712056] Nrf2-dependent suppression of azoxymethane/dextran sulfate sodium-induced colon carcinogenesis by the cinnamon-derived dietary factor cinnamaldehyde. (2015). https://pubmed.ncbi.nlm.nih.gov/25712056/ DOI: 10.1158/1940-6207.capr-14-0359

tissue_or_cell_type

Colon epithelial cancer cells and experimental inflammatory colon tumors

Ceylon cinnamon: metabolism, signaling and nutrient connections (2026-09-17) · lines 623–634

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · HCT116 mechanism and AOM/DSS knockout-mouse experiment · source_derived_draft · unverified_draft

### ceylon-nrf2-gsh Cinnamaldehyde increased cellular glutathione in the HCT116 NRF2-response study. Condition category: normal nutrient_topic: Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect. plain_language: These cells accumulated more glutathione; that does not measure whole-body glutathione supply. organism: Human HCT116 cells; KEAP1 construct species unresolved tissue_or_cell_type: Colon epithelial cancer cells and experimental inflammatory colon tumors experimental_model: HCT116 mechanism and AOM/DSS knockout-mouse experiment limitations: No human cancer-prevention outcome; the abstract identifies C151 dependence but does not resolve the transfected KEAP1 construct species. exposure: Purified cinnamaldehyde cell exposure and dietary supplementation in mice evidence_span: {"source_cache": "artifacts/ceylon-research/25712056.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8ad37b0dca440e7fa609a46cf02377c2979d2be8e09291a370efb963ff3c9cfd", "start_char": 0, "end_char": 1920, "text_sha256": "8ad37b0dca440e7fa609a46cf02377c2979d2be8e09291a370efb963ff3c9cfd"} [ceylon-p25712056] Nrf2-dependent suppression of azoxymethane/dextran sulfate sodium-induced colon carcinogenesis by the cinnamon-derived dietary factor cinnamaldehyde. (2015). https://pubmed.ncbi.nlm.nih.gov/25712056/ DOI: 10.1158/1940-6207.capr-14-0359

evidence_span

{"source_cache": "artifacts/ceylon-research/25712056.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8ad37b0dca440e7fa609a46cf02377c2979d2be8e09291a370efb963ff3c9cfd", "start_char": 0, "end_char": 1920, "text_sha256": "8ad37b0dca440e7fa609a46cf02377c2979d2be8e09291a370efb963ff3c9cfd"}

experimental_model

HCT116 mechanism and AOM/DSS knockout-mouse experiment

exposure

Purified cinnamaldehyde cell exposure and dietary supplementation in mice

limitations

No human cancer-prevention outcome; the abstract identifies C151 dependence but does not resolve the transfected KEAP1 construct species.

nutrient_topic

Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect. · Ceylon cinnamon / Cinnamomum verum bark preparations

organism

Human HCT116 cells; KEAP1 construct species unresolved

plain_language

NRF2 lasted longer, allowing a stronger defense-gene response.

primary_references

[ceylon-p25712056] Nrf2-dependent suppression of azoxymethane/dextran sulfate sodium-induced colon carcinogenesis by the cinnamon-derived dietary factor cinnamaldehyde. (2015). https://pubmed.ncbi.nlm.nih.gov/25712056/ DOI: 10.1158/1940-6207.capr-14-0359

tissue_or_cell_type

Colon epithelial cancer cells and experimental inflammatory colon tumors

Ceylon cinnamon: metabolism, signaling and nutrient connections (2026-09-17) · lines 610–621

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · HCT116 mechanism and AOM/DSS knockout-mouse experiment · source_derived_draft · unverified_draft

### ceylon-nrf2-stability Cinnamaldehyde increased NRF2 protein half-life in HCT116 cells. Condition category: normal nutrient_topic: Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect. plain_language: NRF2 lasted longer, allowing a stronger defense-gene response. organism: Human HCT116 cells; KEAP1 construct species unresolved tissue_or_cell_type: Colon epithelial cancer cells and experimental inflammatory colon tumors experimental_model: HCT116 mechanism and AOM/DSS knockout-mouse experiment limitations: No human cancer-prevention outcome; the abstract identifies C151 dependence but does not resolve the transfected KEAP1 construct species. exposure: Purified cinnamaldehyde cell exposure and dietary supplementation in mice evidence_span: {"source_cache": "artifacts/ceylon-research/25712056.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8ad37b0dca440e7fa609a46cf02377c2979d2be8e09291a370efb963ff3c9cfd", "start_char": 0, "end_char": 1920, "text_sha256": "8ad37b0dca440e7fa609a46cf02377c2979d2be8e09291a370efb963ff3c9cfd"} [ceylon-p25712056] Nrf2-dependent suppression of azoxymethane/dextran sulfate sodium-induced colon carcinogenesis by the cinnamon-derived dietary factor cinnamaldehyde. (2015). https://pubmed.ncbi.nlm.nih.gov/25712056/ DOI: 10.1158/1940-6207.capr-14-0359

evidence_span

{"source_cache": "artifacts/ceylon-research/25712056.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8ad37b0dca440e7fa609a46cf02377c2979d2be8e09291a370efb963ff3c9cfd", "start_char": 0, "end_char": 1920, "text_sha256": "8ad37b0dca440e7fa609a46cf02377c2979d2be8e09291a370efb963ff3c9cfd"}

experimental_model

HCT116 mechanism and AOM/DSS knockout-mouse experiment

exposure

Purified cinnamaldehyde cell exposure and dietary supplementation in mice

limitations

No human cancer-prevention outcome; the abstract identifies C151 dependence but does not resolve the transfected KEAP1 construct species.

nutrient_topic

Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect. · Ceylon cinnamon / Cinnamomum verum bark preparations

organism

Human HCT116 cells; KEAP1 construct species unresolved

plain_language

The cell marked less NRF2 for disposal.

primary_references

[ceylon-p25712056] Nrf2-dependent suppression of azoxymethane/dextran sulfate sodium-induced colon carcinogenesis by the cinnamon-derived dietary factor cinnamaldehyde. (2015). https://pubmed.ncbi.nlm.nih.gov/25712056/ DOI: 10.1158/1940-6207.capr-14-0359

tissue_or_cell_type

Colon epithelial cancer cells and experimental inflammatory colon tumors

Ceylon cinnamon: metabolism, signaling and nutrient connections (2026-09-17) · lines 597–608

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · HCT116 mechanism and AOM/DSS knockout-mouse experiment · source_derived_draft · unverified_draft

### ceylon-nrf2-ubiquitin Cinnamaldehyde blocked NRF2 ubiquitination in HCT116 cells through a KEAP1-C151-dependent mechanism. Condition category: normal nutrient_topic: Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cell marked less NRF2 for disposal. organism: Human HCT116 cells; KEAP1 construct species unresolved tissue_or_cell_type: Colon epithelial cancer cells and experimental inflammatory colon tumors experimental_model: HCT116 mechanism and AOM/DSS knockout-mouse experiment limitations: No human cancer-prevention outcome; the abstract identifies C151 dependence but does not resolve the transfected KEAP1 construct species. exposure: Purified cinnamaldehyde cell exposure and dietary supplementation in mice evidence_span: {"source_cache": "artifacts/ceylon-research/25712056.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8ad37b0dca440e7fa609a46cf02377c2979d2be8e09291a370efb963ff3c9cfd", "start_char": 0, "end_char": 1920, "text_sha256": "8ad37b0dca440e7fa609a46cf02377c2979d2be8e09291a370efb963ff3c9cfd"} [ceylon-p25712056] Nrf2-dependent suppression of azoxymethane/dextran sulfate sodium-induced colon carcinogenesis by the cinnamon-derived dietary factor cinnamaldehyde. (2015). https://pubmed.ncbi.nlm.nih.gov/25712056/ DOI: 10.1158/1940-6207.capr-14-0359

evidence_span

{"source_cache": "artifacts/sulforaphane-research/15572695.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d120b0ea48a77a99b12e9147e4acb02fd63026ed729a37d5e2edf174c5674765", "start_char": 0, "end_char": 1484, "text_sha256": "d120b0ea48a77a99b12e9147e4acb02fd63026ed729a37d5e2edf174c5674765"}

experimental_model

Cell transfection, coimmunoprecipitation and ubiquitination assays

exposure

Sulforaphane or quinone stress; C151S KEAP1 comparison

limitations

The measured interaction is ubiquitin-ligase regulation; do not describe it as obligatory physical release of all bound Nrf2.

nutrient_topic

Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study

organism

Human protein constructs in mammalian cell systems

plain_language

Activating this pathway did not require complete separation of these proteins in the assay.

primary_references

[sulforaphane-p15572695] Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex. (2004). https://pubmed.ncbi.nlm.nih.gov/15572695/ DOI: 10.1128/mcb.24.24.10941-10953.2004

tissue_or_cell_type

KEAP1-CUL3-RBX1 control of Nrf2

Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 489–500

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell transfection, coimmunoprecipitation and ubiquitination assays · source_derived_draft · unverified_draft

### sulforaphane-binding-not-release Sulforaphane did not disrupt the KEAP1-Nrf2 association in the tested interaction assays. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: Activating this pathway did not require complete separation of these proteins in the assay. organism: Human protein constructs in mammalian cell systems tissue_or_cell_type: KEAP1-CUL3-RBX1 control of Nrf2 experimental_model: Cell transfection, coimmunoprecipitation and ubiquitination assays limitations: The measured interaction is ubiquitin-ligase regulation; do not describe it as obligatory physical release of all bound Nrf2. exposure: Sulforaphane or quinone stress; C151S KEAP1 comparison evidence_span: {"source_cache": "artifacts/sulforaphane-research/15572695.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d120b0ea48a77a99b12e9147e4acb02fd63026ed729a37d5e2edf174c5674765", "start_char": 0, "end_char": 1484, "text_sha256": "d120b0ea48a77a99b12e9147e4acb02fd63026ed729a37d5e2edf174c5674765"} [sulforaphane-p15572695] Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex. (2004). https://pubmed.ncbi.nlm.nih.gov/15572695/ DOI: 10.1128/mcb.24.24.10941-10953.2004

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/sulforaphane-research/15572695.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d120b0ea48a77a99b12e9147e4acb02fd63026ed729a37d5e2edf174c5674765", "start_char": 0, "end_char": 1484, "text_sha256": "d120b0ea48a77a99b12e9147e4acb02fd63026ed729a37d5e2edf174c5674765"}

experimental_model

Cell transfection, coimmunoprecipitation and ubiquitination assays

exposure

Sulforaphane or quinone stress; C151S KEAP1 comparison

limitations

The measured interaction is ubiquitin-ligase regulation; do not describe it as obligatory physical release of all bound Nrf2.

nutrient_topic

Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study

organism

Human protein constructs in mammalian cell systems

plain_language

An altered sensor can block the response even when the compound is present.

primary_references

[sulforaphane-p15572695] Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex. (2004). https://pubmed.ncbi.nlm.nih.gov/15572695/ DOI: 10.1128/mcb.24.24.10941-10953.2004

tissue_or_cell_type

KEAP1-CUL3-RBX1 control of Nrf2

trigger_kind

machinery_impairment Imported condition classification; unverified.

Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 502–513

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell transfection, coimmunoprecipitation and ubiquitination assays · source_derived_draft · unverified_draft

### sulforaphane-c151s-response KEAP1 C151S was markedly resistant to sulforaphane inhibition of its Nrf2-ubiquitination function. Condition category: machinery_impairment nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: An altered sensor can block the response even when the compound is present. organism: Human protein constructs in mammalian cell systems tissue_or_cell_type: KEAP1-CUL3-RBX1 control of Nrf2 experimental_model: Cell transfection, coimmunoprecipitation and ubiquitination assays limitations: The measured interaction is ubiquitin-ligase regulation; do not describe it as obligatory physical release of all bound Nrf2. exposure: Sulforaphane or quinone stress; C151S KEAP1 comparison evidence_span: {"source_cache": "artifacts/sulforaphane-research/15572695.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d120b0ea48a77a99b12e9147e4acb02fd63026ed729a37d5e2edf174c5674765", "start_char": 0, "end_char": 1484, "text_sha256": "d120b0ea48a77a99b12e9147e4acb02fd63026ed729a37d5e2edf174c5674765"} [sulforaphane-p15572695] Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex. (2004). https://pubmed.ncbi.nlm.nih.gov/15572695/ DOI: 10.1128/mcb.24.24.10941-10953.2004

evidence_span

{"source_cache": "artifacts/sulforaphane-research/15572695.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d120b0ea48a77a99b12e9147e4acb02fd63026ed729a37d5e2edf174c5674765", "start_char": 0, "end_char": 1484, "text_sha256": "d120b0ea48a77a99b12e9147e4acb02fd63026ed729a37d5e2edf174c5674765"}

experimental_model

Cell transfection, coimmunoprecipitation and ubiquitination assays

exposure

Sulforaphane or quinone stress; C151S KEAP1 comparison

limitations

The measured interaction is ubiquitin-ligase regulation; do not describe it as obligatory physical release of all bound Nrf2.

nutrient_topic

Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study

organism

Human protein constructs in mammalian cell systems

plain_language

The sensor helps bring the protein targeted for disposal to the disposal machinery.

primary_references

[sulforaphane-p15572695] Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex. (2004). https://pubmed.ncbi.nlm.nih.gov/15572695/ DOI: 10.1128/mcb.24.24.10941-10953.2004

tissue_or_cell_type

KEAP1-CUL3-RBX1 control of Nrf2

Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 450–461

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell transfection, coimmunoprecipitation and ubiquitination assays · source_derived_draft · unverified_draft

### sulforaphane-keap1-ligase KEAP1 acted as a substrate adaptor in a functional CUL3-RBX1 ubiquitin-ligase complex. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: The sensor helps bring the protein targeted for disposal to the disposal machinery. organism: Human protein constructs in mammalian cell systems tissue_or_cell_type: KEAP1-CUL3-RBX1 control of Nrf2 experimental_model: Cell transfection, coimmunoprecipitation and ubiquitination assays limitations: The measured interaction is ubiquitin-ligase regulation; do not describe it as obligatory physical release of all bound Nrf2. exposure: Sulforaphane or quinone stress; C151S KEAP1 comparison evidence_span: {"source_cache": "artifacts/sulforaphane-research/15572695.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d120b0ea48a77a99b12e9147e4acb02fd63026ed729a37d5e2edf174c5674765", "start_char": 0, "end_char": 1484, "text_sha256": "d120b0ea48a77a99b12e9147e4acb02fd63026ed729a37d5e2edf174c5674765"} [sulforaphane-p15572695] Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex. (2004). https://pubmed.ncbi.nlm.nih.gov/15572695/ DOI: 10.1128/mcb.24.24.10941-10953.2004

evidence_span

{"source_cache": "artifacts/sulforaphane-research/27636860.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "38b05ba233878d75f74373f3093e4d51bbbbb417b59f06dec578f7c293e12793", "start_char": 0, "end_char": 1177, "text_sha256": "38b05ba233878d75f74373f3093e4d51bbbbb417b59f06dec578f7c293e12793"}

experimental_model

Gene and enzyme-response comparison

exposure

Sulforaphane exposure across three cell contexts

limitations

Cancer and untransformed cells regulated the pathway differently; no claim that all Nrf2 activation is desirable in established tumors.

nutrient_topic

Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study

organism

Human CRL-1790 untransformed colon cells, HT-29 and Caco-2 cancer cells

plain_language

The response can increase an export transporter as well as enzymes.

primary_references

[sulforaphane-p27636860] Sulforaphane Regulates NFE2L2/Nrf2-Dependent Xenobiotic Metabolism Phase II and Phase III Enzymes Differently in Human Colorectal Cancer and Untransformed Epithelial Colon Cells. (2016). https://pubmed.ncbi.nlm.nih.gov/27636860/ DOI: 10.1080/01635581.2016.1224369

tissue_or_cell_type

Nrf2 targets and cell defense

Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 554–565

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Gene and enzyme-response comparison · source_derived_draft · unverified_draft

### sulforaphane-mrp1-induction Sulforaphane induced Nrf2-dependent MRP1 expression in CRL-1790 cells. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: The response can increase an export transporter as well as enzymes. organism: Human CRL-1790 untransformed colon cells, HT-29 and Caco-2 cancer cells tissue_or_cell_type: Nrf2 targets and cell defense experimental_model: Gene and enzyme-response comparison limitations: Cancer and untransformed cells regulated the pathway differently; no claim that all Nrf2 activation is desirable in established tumors. exposure: Sulforaphane exposure across three cell contexts evidence_span: {"source_cache": "artifacts/sulforaphane-research/27636860.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "38b05ba233878d75f74373f3093e4d51bbbbb417b59f06dec578f7c293e12793", "start_char": 0, "end_char": 1177, "text_sha256": "38b05ba233878d75f74373f3093e4d51bbbbb417b59f06dec578f7c293e12793"} [sulforaphane-p27636860] Sulforaphane Regulates NFE2L2/Nrf2-Dependent Xenobiotic Metabolism Phase II and Phase III Enzymes Differently in Human Colorectal Cancer and Untransformed Epithelial Colon Cells. (2016). https://pubmed.ncbi.nlm.nih.gov/27636860/ DOI: 10.1080/01635581.2016.1224369

evidence_span

{"source_cache": "artifacts/sulforaphane-research/27636860.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "38b05ba233878d75f74373f3093e4d51bbbbb417b59f06dec578f7c293e12793", "start_char": 0, "end_char": 1177, "text_sha256": "38b05ba233878d75f74373f3093e4d51bbbbb417b59f06dec578f7c293e12793"}

experimental_model

Gene and enzyme-response comparison

exposure

Sulforaphane exposure across three cell contexts

limitations

Cancer and untransformed cells regulated the pathway differently; no claim that all Nrf2 activation is desirable in established tumors.

nutrient_topic

Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study

organism

Human CRL-1790 untransformed colon cells, HT-29 and Caco-2 cancer cells

plain_language

One induced enzyme handles quinone chemistry.

primary_references

[sulforaphane-p27636860] Sulforaphane Regulates NFE2L2/Nrf2-Dependent Xenobiotic Metabolism Phase II and Phase III Enzymes Differently in Human Colorectal Cancer and Untransformed Epithelial Colon Cells. (2016). https://pubmed.ncbi.nlm.nih.gov/27636860/ DOI: 10.1080/01635581.2016.1224369

tissue_or_cell_type

Nrf2 targets and cell defense

Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 541–552

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Gene and enzyme-response comparison · source_derived_draft · unverified_draft

### sulforaphane-nqo1-induction Sulforaphane induced Nrf2-dependent NQO1 expression in untransformed human CRL-1790 colon cells. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: One induced enzyme handles quinone chemistry. organism: Human CRL-1790 untransformed colon cells, HT-29 and Caco-2 cancer cells tissue_or_cell_type: Nrf2 targets and cell defense experimental_model: Gene and enzyme-response comparison limitations: Cancer and untransformed cells regulated the pathway differently; no claim that all Nrf2 activation is desirable in established tumors. exposure: Sulforaphane exposure across three cell contexts evidence_span: {"source_cache": "artifacts/sulforaphane-research/27636860.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "38b05ba233878d75f74373f3093e4d51bbbbb417b59f06dec578f7c293e12793", "start_char": 0, "end_char": 1177, "text_sha256": "38b05ba233878d75f74373f3093e4d51bbbbb417b59f06dec578f7c293e12793"} [sulforaphane-p27636860] Sulforaphane Regulates NFE2L2/Nrf2-Dependent Xenobiotic Metabolism Phase II and Phase III Enzymes Differently in Human Colorectal Cancer and Untransformed Epithelial Colon Cells. (2016). https://pubmed.ncbi.nlm.nih.gov/27636860/ DOI: 10.1080/01635581.2016.1224369

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/sulforaphane-research/26094214.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "de55004b06332873c312c03a18cec65eeb22c1bab6daddf5cde8a7977817567e", "start_char": 0, "end_char": 1568, "text_sha256": "de55004b06332873c312c03a18cec65eeb22c1bab6daddf5cde8a7977817567e"}

experimental_model

Combination treatment and siRNA loss-of-function

exposure

Sulforaphane plus selenium with Nrf2 or TXNRD1 knockdown

limitations

One cell model; survival percentages are assay-specific and not clinical benefit estimates.

nutrient_topic

Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study

organism

Human nontransformed CCD841 colonic cells

plain_language

The regulator was necessary for much of the observed protection.

primary_references

[sulforaphane-p26094214] Synergy between sulforaphane and selenium in protection against oxidative damage in colonic CCD841 cells. (2015). https://pubmed.ncbi.nlm.nih.gov/26094214/ DOI: 10.1016/j.nutres.2015.05.011

tissue_or_cell_type

Nrf2/TXNRD1 and peroxide survival

trigger_kind

machinery_impairment Imported condition classification; unverified.

Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 788–799

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Combination treatment and siRNA loss-of-function · source_derived_draft · unverified_draft

### sulforaphane-nrf2-knockdown Nrf2 knockdown lowered survival under combined treatment from 82.4% to 51.1%. Condition category: machinery_impairment nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: The regulator was necessary for much of the observed protection. organism: Human nontransformed CCD841 colonic cells tissue_or_cell_type: Nrf2/TXNRD1 and peroxide survival experimental_model: Combination treatment and siRNA loss-of-function limitations: One cell model; survival percentages are assay-specific and not clinical benefit estimates. exposure: Sulforaphane plus selenium with Nrf2 or TXNRD1 knockdown evidence_span: {"source_cache": "artifacts/sulforaphane-research/26094214.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "de55004b06332873c312c03a18cec65eeb22c1bab6daddf5cde8a7977817567e", "start_char": 0, "end_char": 1568, "text_sha256": "de55004b06332873c312c03a18cec65eeb22c1bab6daddf5cde8a7977817567e"} [sulforaphane-p26094214] Synergy between sulforaphane and selenium in protection against oxidative damage in colonic CCD841 cells. (2015). https://pubmed.ncbi.nlm.nih.gov/26094214/ DOI: 10.1016/j.nutres.2015.05.011

evidence_span

{"source_cache": "artifacts/sulforaphane-research/14585973.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bc2e1304879d9bd3d1b4946981f93a78d3f604c580ea252af17f645e237cadd0", "start_char": 0, "end_char": 1647, "text_sha256": "bc2e1304879d9bd3d1b4946981f93a78d3f604c580ea252af17f645e237cadd0"}

experimental_model

KEAP1 mutagenesis and Nrf2 stability/localization assays

exposure

Sulforaphane or oxidative stress; C151/C273/C288 variants

limitations

Individual cysteines have different roles; activating Nrf2 does not establish prevention or treatment of cancer in humans.

nutrient_topic

Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study

organism

Human KEAP1 constructs in cellular experiments

plain_language

The regulator accumulates where it can influence gene expression.

primary_references

[sulforaphane-p14585973] Distinct cysteine residues in Keap1 are required for Keap1-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress. (2003). https://pubmed.ncbi.nlm.nih.gov/14585973/ DOI: 10.1128/mcb.23.22.8137-8151.2003

tissue_or_cell_type

Ubiquitination, protein turnover and nuclear localization

Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 528–539

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · KEAP1 mutagenesis and Nrf2 stability/localization assays · source_derived_draft · unverified_draft

### sulforaphane-nrf2-nuclear Sulforaphane increased nuclear localization of stabilized Nrf2 and Nrf2-dependent gene activation. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: The regulator accumulates where it can influence gene expression. organism: Human KEAP1 constructs in cellular experiments tissue_or_cell_type: Ubiquitination, protein turnover and nuclear localization experimental_model: KEAP1 mutagenesis and Nrf2 stability/localization assays limitations: Individual cysteines have different roles; activating Nrf2 does not establish prevention or treatment of cancer in humans. exposure: Sulforaphane or oxidative stress; C151/C273/C288 variants evidence_span: {"source_cache": "artifacts/sulforaphane-research/14585973.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bc2e1304879d9bd3d1b4946981f93a78d3f604c580ea252af17f645e237cadd0", "start_char": 0, "end_char": 1647, "text_sha256": "bc2e1304879d9bd3d1b4946981f93a78d3f604c580ea252af17f645e237cadd0"} [sulforaphane-p14585973] Distinct cysteine residues in Keap1 are required for Keap1-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress. (2003). https://pubmed.ncbi.nlm.nih.gov/14585973/ DOI: 10.1128/mcb.23.22.8137-8151.2003

evidence_span

{"source_cache": "artifacts/sulforaphane-research/14585973.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bc2e1304879d9bd3d1b4946981f93a78d3f604c580ea252af17f645e237cadd0", "start_char": 0, "end_char": 1647, "text_sha256": "bc2e1304879d9bd3d1b4946981f93a78d3f604c580ea252af17f645e237cadd0"}

experimental_model

KEAP1 mutagenesis and Nrf2 stability/localization assays

exposure

Sulforaphane or oxidative stress; C151/C273/C288 variants

limitations

Individual cysteines have different roles; activating Nrf2 does not establish prevention or treatment of cancer in humans.

nutrient_topic

Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study

organism

Human KEAP1 constructs in cellular experiments

plain_language

The cell keeps more of the regulator available.

primary_references

[sulforaphane-p14585973] Distinct cysteine residues in Keap1 are required for Keap1-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress. (2003). https://pubmed.ncbi.nlm.nih.gov/14585973/ DOI: 10.1128/mcb.23.22.8137-8151.2003

tissue_or_cell_type

Ubiquitination, protein turnover and nuclear localization

Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 515–526

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · KEAP1 mutagenesis and Nrf2 stability/localization assays · source_derived_draft · unverified_draft

### sulforaphane-nrf2-stability Sulforaphane enabled Nrf2 to escape KEAP1-dependent degradation and increased its stability. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cell keeps more of the regulator available. organism: Human KEAP1 constructs in cellular experiments tissue_or_cell_type: Ubiquitination, protein turnover and nuclear localization experimental_model: KEAP1 mutagenesis and Nrf2 stability/localization assays limitations: Individual cysteines have different roles; activating Nrf2 does not establish prevention or treatment of cancer in humans. exposure: Sulforaphane or oxidative stress; C151/C273/C288 variants evidence_span: {"source_cache": "artifacts/sulforaphane-research/14585973.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bc2e1304879d9bd3d1b4946981f93a78d3f604c580ea252af17f645e237cadd0", "start_char": 0, "end_char": 1647, "text_sha256": "bc2e1304879d9bd3d1b4946981f93a78d3f604c580ea252af17f645e237cadd0"} [sulforaphane-p14585973] Distinct cysteine residues in Keap1 are required for Keap1-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress. (2003). https://pubmed.ncbi.nlm.nih.gov/14585973/ DOI: 10.1128/mcb.23.22.8137-8151.2003

evidence_span

{"source_cache": "artifacts/sulforaphane-research/15572695.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d120b0ea48a77a99b12e9147e4acb02fd63026ed729a37d5e2edf174c5674765", "start_char": 0, "end_char": 1484, "text_sha256": "d120b0ea48a77a99b12e9147e4acb02fd63026ed729a37d5e2edf174c5674765"}

experimental_model

Cell transfection, coimmunoprecipitation and ubiquitination assays

exposure

Sulforaphane or quinone stress; C151S KEAP1 comparison

limitations

The measured interaction is ubiquitin-ligase regulation; do not describe it as obligatory physical release of all bound Nrf2.

nutrient_topic

Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study

organism

Human protein constructs in mammalian cell systems

plain_language

Less disposal allows the regulator to persist.

primary_references

[sulforaphane-p15572695] Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex. (2004). https://pubmed.ncbi.nlm.nih.gov/15572695/ DOI: 10.1128/mcb.24.24.10941-10953.2004

tissue_or_cell_type

KEAP1-CUL3-RBX1 control of Nrf2

Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 476–487

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell transfection, coimmunoprecipitation and ubiquitination assays · source_derived_draft · unverified_draft

### sulforaphane-sfn-ubiquitination Sulforaphane inhibited KEAP1-dependent ubiquitination of Nrf2. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: Less disposal allows the regulator to persist. organism: Human protein constructs in mammalian cell systems tissue_or_cell_type: KEAP1-CUL3-RBX1 control of Nrf2 experimental_model: Cell transfection, coimmunoprecipitation and ubiquitination assays limitations: The measured interaction is ubiquitin-ligase regulation; do not describe it as obligatory physical release of all bound Nrf2. exposure: Sulforaphane or quinone stress; C151S KEAP1 comparison evidence_span: {"source_cache": "artifacts/sulforaphane-research/15572695.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d120b0ea48a77a99b12e9147e4acb02fd63026ed729a37d5e2edf174c5674765", "start_char": 0, "end_char": 1484, "text_sha256": "d120b0ea48a77a99b12e9147e4acb02fd63026ed729a37d5e2edf174c5674765"} [sulforaphane-p15572695] Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex. (2004). https://pubmed.ncbi.nlm.nih.gov/15572695/ DOI: 10.1128/mcb.24.24.10941-10953.2004

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/sulforaphane-research/26094214.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "de55004b06332873c312c03a18cec65eeb22c1bab6daddf5cde8a7977817567e", "start_char": 0, "end_char": 1568, "text_sha256": "de55004b06332873c312c03a18cec65eeb22c1bab6daddf5cde8a7977817567e"}

experimental_model

Combination treatment and siRNA loss-of-function

exposure

Sulforaphane plus selenium with Nrf2 or TXNRD1 knockdown

limitations

One cell model; survival percentages are assay-specific and not clinical benefit estimates.

nutrient_topic

Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study

organism

Human nontransformed CCD841 colonic cells

plain_language

Increasing the signal cannot replace the enzyme that carries out part of the response.

primary_references

[sulforaphane-p26094214] Synergy between sulforaphane and selenium in protection against oxidative damage in colonic CCD841 cells. (2015). https://pubmed.ncbi.nlm.nih.gov/26094214/ DOI: 10.1016/j.nutres.2015.05.011

tissue_or_cell_type

Nrf2/TXNRD1 and peroxide survival

trigger_kind

machinery_impairment Imported condition classification; unverified.

Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 775–786

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Combination treatment and siRNA loss-of-function · source_derived_draft · unverified_draft

### sulforaphane-txnrd1-knockdown TXNRD1 knockdown lowered survival under combined treatment from 82.4% to 66.5% in the peroxide-challenge assay. Condition category: machinery_impairment nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: Increasing the signal cannot replace the enzyme that carries out part of the response. organism: Human nontransformed CCD841 colonic cells tissue_or_cell_type: Nrf2/TXNRD1 and peroxide survival experimental_model: Combination treatment and siRNA loss-of-function limitations: One cell model; survival percentages are assay-specific and not clinical benefit estimates. exposure: Sulforaphane plus selenium with Nrf2 or TXNRD1 knockdown evidence_span: {"source_cache": "artifacts/sulforaphane-research/26094214.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "de55004b06332873c312c03a18cec65eeb22c1bab6daddf5cde8a7977817567e", "start_char": 0, "end_char": 1568, "text_sha256": "de55004b06332873c312c03a18cec65eeb22c1bab6daddf5cde8a7977817567e"} [sulforaphane-p26094214] Synergy between sulforaphane and selenium in protection against oxidative damage in colonic CCD841 cells. (2015). https://pubmed.ncbi.nlm.nih.gov/26094214/ DOI: 10.1016/j.nutres.2015.05.011

evidence_span

{"source_cache": "artifacts/mangiferin-research/24626801.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "01992b219c903dddc6e69f5fef95f73cec06cdaac0fd2c5bc2ff7b53b52192cd", "start_char": 0, "end_char": 1659, "text_sha256": "01992b219c903dddc6e69f5fef95f73cec06cdaac0fd2c5bc2ff7b53b52192cd"}

experimental_model

Cycloheximide chase and immunoprecipitation

exposure

Mangiferin 50 micromolar for four hours in half-life experiment

limitations

Cancer cell line; no direct KEAP1-binding assignment or human systemic target-engagement inference.

nutrient_topic

Mangiferin research collection; topical membership is not evidence of a direct dietary effect. · Mangiferin

organism

Homo sapiens

plain_language

The protein persisted longer before degradation.

primary_references

[mangiferin-p24626801] Mangiferin increases Nrf2 protein stability by inhibiting its ubiquitination and degradation in human HL60 myeloid leukemia cells. (2014). https://pubmed.ncbi.nlm.nih.gov/24626801/ DOI: 10.3892/ijmm.2014.1696

tissue_or_cell_type

HL-60 myeloid leukemia cells

Mangiferin: metabolism, signaling and nutrient connections (2026-09-17) · lines 523–534

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cycloheximide chase and immunoprecipitation · source_derived_draft · unverified_draft

### mangiferin-nrf2-half-life Nrf2 half-life increased from 20 to 58 minutes in the HL-60 chase experiment. Condition category: normal nutrient_topic: Mangiferin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The protein persisted longer before degradation. organism: Homo sapiens tissue_or_cell_type: HL-60 myeloid leukemia cells experimental_model: Cycloheximide chase and immunoprecipitation limitations: Cancer cell line; no direct KEAP1-binding assignment or human systemic target-engagement inference. exposure: Mangiferin 50 micromolar for four hours in half-life experiment evidence_span: {"source_cache": "artifacts/mangiferin-research/24626801.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "01992b219c903dddc6e69f5fef95f73cec06cdaac0fd2c5bc2ff7b53b52192cd", "start_char": 0, "end_char": 1659, "text_sha256": "01992b219c903dddc6e69f5fef95f73cec06cdaac0fd2c5bc2ff7b53b52192cd"} [mangiferin-p24626801] Mangiferin increases Nrf2 protein stability by inhibiting its ubiquitination and degradation in human HL60 myeloid leukemia cells. (2014). https://pubmed.ncbi.nlm.nih.gov/24626801/ DOI: 10.3892/ijmm.2014.1696

evidence_span

{"source_cache": "artifacts/mangiferin-research/24626801.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "01992b219c903dddc6e69f5fef95f73cec06cdaac0fd2c5bc2ff7b53b52192cd", "start_char": 0, "end_char": 1659, "text_sha256": "01992b219c903dddc6e69f5fef95f73cec06cdaac0fd2c5bc2ff7b53b52192cd"}

experimental_model

Cycloheximide chase and immunoprecipitation

exposure

Mangiferin 50 micromolar for four hours in half-life experiment

limitations

Cancer cell line; no direct KEAP1-binding assignment or human systemic target-engagement inference.

nutrient_topic

Mangiferin research collection; topical membership is not evidence of a direct dietary effect. · Mangiferin

organism

Homo sapiens

plain_language

Less degradation-associated tagging was detected.

primary_references

[mangiferin-p24626801] Mangiferin increases Nrf2 protein stability by inhibiting its ubiquitination and degradation in human HL60 myeloid leukemia cells. (2014). https://pubmed.ncbi.nlm.nih.gov/24626801/ DOI: 10.3892/ijmm.2014.1696

tissue_or_cell_type

HL-60 myeloid leukemia cells

Mangiferin: metabolism, signaling and nutrient connections (2026-09-17) · lines 536–547

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cycloheximide chase and immunoprecipitation · source_derived_draft · unverified_draft

### mangiferin-nrf2-ubiquitination Immunoprecipitation showed reduced Nrf2 ubiquitination after mangiferin treatment. Condition category: normal nutrient_topic: Mangiferin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Less degradation-associated tagging was detected. organism: Homo sapiens tissue_or_cell_type: HL-60 myeloid leukemia cells experimental_model: Cycloheximide chase and immunoprecipitation limitations: Cancer cell line; no direct KEAP1-binding assignment or human systemic target-engagement inference. exposure: Mangiferin 50 micromolar for four hours in half-life experiment evidence_span: {"source_cache": "artifacts/mangiferin-research/24626801.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "01992b219c903dddc6e69f5fef95f73cec06cdaac0fd2c5bc2ff7b53b52192cd", "start_char": 0, "end_char": 1659, "text_sha256": "01992b219c903dddc6e69f5fef95f73cec06cdaac0fd2c5bc2ff7b53b52192cd"} [mangiferin-p24626801] Mangiferin increases Nrf2 protein stability by inhibiting its ubiquitination and degradation in human HL60 myeloid leukemia cells. (2014). https://pubmed.ncbi.nlm.nih.gov/24626801/ DOI: 10.3892/ijmm.2014.1696

evidence_span

{"source_cache": "artifacts/ala-research/18813798.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bcc2d2fa7c8f550c53af52dfcd88a1e84bee38f98b85cb72e723eba495b01814", "start_char": 0, "end_char": 1245, "text_sha256": "bcc2d2fa7c8f550c53af52dfcd88a1e84bee38f98b85cb72e723eba495b01814"}

experimental_model

Human HL-60 leukemia cell biochemical study

exposure

Alpha-lipoic-acid exposure

limitations

Association of Nrf2/KEAP1 changes with NQO1 induction does not by itself establish genetic dependency or clinical cancer benefit.

nutrient_topic

Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid

organism

Human cell line

plain_language

The response included more activity of a specific quinone-processing enzyme.

primary_references

[ala-p18813798] Control of cellular redox status and upregulation of quinone reductase NQO1 via Nrf2 activation by alpha-lipoic acid in human leukemia HL-60 cells. (2008). https://pubmed.ncbi.nlm.nih.gov/18813798/ DOI: 10.3892/ijo_00000071

tissue_or_cell_type

HL-60 cells

Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 884–895

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human HL-60 leukemia cell biochemical study · source_derived_draft · unverified_draft

### ala-hl60-nqo1 NQO1 protein and enzyme activity increased after lipoic-acid treatment in HL-60 cells. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The response included more activity of a specific quinone-processing enzyme. organism: Human cell line tissue_or_cell_type: HL-60 cells experimental_model: Human HL-60 leukemia cell biochemical study limitations: Association of Nrf2/KEAP1 changes with NQO1 induction does not by itself establish genetic dependency or clinical cancer benefit. exposure: Alpha-lipoic-acid exposure evidence_span: {"source_cache": "artifacts/ala-research/18813798.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bcc2d2fa7c8f550c53af52dfcd88a1e84bee38f98b85cb72e723eba495b01814", "start_char": 0, "end_char": 1245, "text_sha256": "bcc2d2fa7c8f550c53af52dfcd88a1e84bee38f98b85cb72e723eba495b01814"} [ala-p18813798] Control of cellular redox status and upregulation of quinone reductase NQO1 via Nrf2 activation by alpha-lipoic acid in human leukemia HL-60 cells. (2008). https://pubmed.ncbi.nlm.nih.gov/18813798/ DOI: 10.3892/ijo_00000071

evidence_span

{"source_cache": "artifacts/ala-research/18813798.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bcc2d2fa7c8f550c53af52dfcd88a1e84bee38f98b85cb72e723eba495b01814", "start_char": 0, "end_char": 1245, "text_sha256": "bcc2d2fa7c8f550c53af52dfcd88a1e84bee38f98b85cb72e723eba495b01814"}

experimental_model

Human HL-60 leukemia cell biochemical study

exposure

Alpha-lipoic-acid exposure

limitations

Association of Nrf2/KEAP1 changes with NQO1 induction does not by itself establish genetic dependency or clinical cancer benefit.

nutrient_topic

Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid

organism

Human cell line

plain_language

A cellular stress-response regulator changed location while its inhibitor decreased.

primary_references

[ala-p18813798] Control of cellular redox status and upregulation of quinone reductase NQO1 via Nrf2 activation by alpha-lipoic acid in human leukemia HL-60 cells. (2008). https://pubmed.ncbi.nlm.nih.gov/18813798/ DOI: 10.3892/ijo_00000071

tissue_or_cell_type

HL-60 cells

Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 871–882

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human HL-60 leukemia cell biochemical study · source_derived_draft · unverified_draft

### ala-hl60-nrf2-keap1 Lipoic-acid exposure increased nuclear Nrf2 and reduced KEAP1 protein in HL-60 cells. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: A cellular stress-response regulator changed location while its inhibitor decreased. organism: Human cell line tissue_or_cell_type: HL-60 cells experimental_model: Human HL-60 leukemia cell biochemical study limitations: Association of Nrf2/KEAP1 changes with NQO1 induction does not by itself establish genetic dependency or clinical cancer benefit. exposure: Alpha-lipoic-acid exposure evidence_span: {"source_cache": "artifacts/ala-research/18813798.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bcc2d2fa7c8f550c53af52dfcd88a1e84bee38f98b85cb72e723eba495b01814", "start_char": 0, "end_char": 1245, "text_sha256": "bcc2d2fa7c8f550c53af52dfcd88a1e84bee38f98b85cb72e723eba495b01814"} [ala-p18813798] Control of cellular redox status and upregulation of quinone reductase NQO1 via Nrf2 activation by alpha-lipoic acid in human leukemia HL-60 cells. (2008). https://pubmed.ncbi.nlm.nih.gov/18813798/ DOI: 10.3892/ijo_00000071

evidence_span

{"source_cache": "artifacts/berberine-research/29891588.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e59ba2b3b6e505cf3b220d32040e37f53553ea73427dd522cf7ea237d7d0f405", "start_char": 0, "end_char": 1752, "text_sha256": "e59ba2b3b6e505cf3b220d32040e37f53553ea73427dd522cf7ea237d7d0f405"}

experimental_model

Nrf2 reporter, gene silencing and expression assays

exposure

Berberine concentration and time response

limitations

Transporter expression after prolonged exposure is not the same endpoint as acute competitive inhibition. Rat colitis improvement does not establish human IBD efficacy.

nutrient_topic

Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine

organism

Human Caco-2 cells; rat colitis in a separate arm

plain_language

Repeated exposure can increase the pump that exports drugs.

primary_references

[berberine-p29891588] Berberine Upregulates P-Glycoprotein in Human Caco-2 Cells and in an Experimental Model of Colitis in the Rat via Activation of Nrf2-Dependent Mechanisms. (2018). https://pubmed.ncbi.nlm.nih.gov/29891588/ DOI: 10.1124/jpet.118.249615

tissue_or_cell_type

Nrf2-dependent ABCB1 expression

Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 545–556

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Nrf2 reporter, gene silencing and expression assays · source_derived_draft · unverified_draft

### berberine-abcb1-expression Berberine increased MDR1/ABCB1 expression; Nrf2 silencing abolished the gene response in Caco-2 cells. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Repeated exposure can increase the pump that exports drugs. organism: Human Caco-2 cells; rat colitis in a separate arm tissue_or_cell_type: Nrf2-dependent ABCB1 expression experimental_model: Nrf2 reporter, gene silencing and expression assays limitations: Transporter expression after prolonged exposure is not the same endpoint as acute competitive inhibition. Rat colitis improvement does not establish human IBD efficacy. exposure: Berberine concentration and time response evidence_span: {"source_cache": "artifacts/berberine-research/29891588.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e59ba2b3b6e505cf3b220d32040e37f53553ea73427dd522cf7ea237d7d0f405", "start_char": 0, "end_char": 1752, "text_sha256": "e59ba2b3b6e505cf3b220d32040e37f53553ea73427dd522cf7ea237d7d0f405"} [berberine-p29891588] Berberine Upregulates P-Glycoprotein in Human Caco-2 Cells and in an Experimental Model of Colitis in the Rat via Activation of Nrf2-Dependent Mechanisms. (2018). https://pubmed.ncbi.nlm.nih.gov/29891588/ DOI: 10.1124/jpet.118.249615

evidence_span

{"source_cache": "artifacts/boron-research/30196486.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e220df5fb0f9b8653035f7a144259ce66778467a7a72acbf7cd7d113f8b6030a", "start_char": 0, "end_char": 2006, "text_sha256": "e220df5fb0f9b8653035f7a144259ce66778467a7a72acbf7cd7d113f8b6030a"}

experimental_model

PERK knockout comparison, immunofluorescence and quantitative PCR

exposure

10 µM boric acid; 1–6 hour comparisons

limitations

Knockout dependence in mouse fibroblasts is separate from human tumor-cell transcription. Increased GCLC mRNA is not a measured increase in glutathione synthesis or clinical antioxidant benefit.

nutrient_topic

Boron research collection; topical membership is not evidence of a direct dietary effect. · Boron

organism

Human

plain_language

An antioxidant-response regulator moved to the place where it can influence gene expression.

primary_references

[boron-p30196486] Boric Acid Activation of eIF2α and Nrf2 Is PERK Dependent: a Mechanism that Explains How Boron Prevents DNA Damage and Enhances Antioxidant Status. (2019). https://pubmed.ncbi.nlm.nih.gov/30196486/ DOI: 10.1007/s12011-018-1498-4

tissue_or_cell_type

DU-145 prostate cancer cell culture

Boron: chemistry, nutrient interactions, low-intake studies and mechanistic uncertainties (2026-09-17) · lines 521–532

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · PERK knockout comparison, immunofluorescence and quantitative PCR · source_derived_draft · unverified_draft

### boron-human-nrf2-localization Nrf2 moved from the cytoplasm to the nucleus at 1.5–2 hours after boric-acid treatment of human DU-145 cells. Condition category: normal nutrient_topic: Boron research collection; topical membership is not evidence of a direct dietary effect. plain_language: An antioxidant-response regulator moved to the place where it can influence gene expression. organism: Human tissue_or_cell_type: DU-145 prostate cancer cell culture experimental_model: PERK knockout comparison, immunofluorescence and quantitative PCR limitations: Knockout dependence in mouse fibroblasts is separate from human tumor-cell transcription. Increased GCLC mRNA is not a measured increase in glutathione synthesis or clinical antioxidant benefit. exposure: 10 µM boric acid; 1–6 hour comparisons evidence_span: {"source_cache": "artifacts/boron-research/30196486.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e220df5fb0f9b8653035f7a144259ce66778467a7a72acbf7cd7d113f8b6030a", "start_char": 0, "end_char": 2006, "text_sha256": "e220df5fb0f9b8653035f7a144259ce66778467a7a72acbf7cd7d113f8b6030a"} [boron-p30196486] Boric Acid Activation of eIF2α and Nrf2 Is PERK Dependent: a Mechanism that Explains How Boron Prevents DNA Damage and Enhances Antioxidant Status. (2019). https://pubmed.ncbi.nlm.nih.gov/30196486/ DOI: 10.1007/s12011-018-1498-4

evidence_access

Primary full text

experimental_model

Human-cell proteasome activity and protein-stability assays.

limitations

Not proof that spermidine directly binds a specific proteasome subunit.

nutrient_topic

Spermidine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Spermidine

plain_language

Protein accumulation can involve slower removal as well as faster production.

primary_references

Spermidine inactivates proteasome activity and enhances ferroptosis in prostate cancer. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40486852/ · DOI 10.1016/j.apsb.2025.02.023

Spermidine: biosynthesis, hypusination, transport and cross-nutrient mechanisms (2026-09-19) · lines 518–524

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human-cell proteasome activity and protein-stability assays. · source_derived_draft · unverified_draft

## spermidine-proteasome Protein accumulation can involve slower removal as well as faster production. Spermidine/erastin treatment reduced proteasome activity and NRF2 degradation in the reported prostate-cell experiments. Model: Human-cell proteasome activity and protein-stability assays. Limitations: Not proof that spermidine directly binds a specific proteasome subunit. Evidence access: Primary full text Spermidine inactivates proteasome activity and enhances ferroptosis in prostate cancer. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40486852/ · DOI 10.1016/j.apsb.2025.02.023

duration

Not stated here

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

RAW 264.7 murine macrophages

exposure

(+)-Lariciresinol

limitations

The abstract reports the rise in HO-1 as corresponding to the rise in Nrf2; the causal test by Nrf2 inhibition is described in the full text and was not read here.

organism

RAW 264.7 murine macrophages

plain_language

(+)-Lariciresinol increased heme oxygenase 1 at both transcriptional and translational levels, alongside the rise in Nrf2.

primary_references

Antioxidant efficacy and the upregulation of Nrf2-mediated HO-1 expression by (+)-lariciresinol, a lignan isolated from Rubia philippinensis, through the activation of p38. (2017). https://pubmed.ncbi.nlm.nih.gov/28378774/ DOI: 10.1038/srep46035

route

In vitro

tissue

Heme oxygenase 1 expression

Lariciresinol: five molecules under one name, and the mechanisms each one carries (2026-09-22) · lines 44–53

Original AI-assisted curation of twelve primary studies, every abstract read and all DOIs cross-checked against live PubMed metadata. Mechanism edges only, with no conclusion or claim of benefit recorded. Three author clusters account for eight of the twelve and carry shared laboratory keys. Study-specific concentrations, negative findings and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

## plus-lariciresinol-raises-heme-oxygenase-1 (+)-Lariciresinol increased heme oxygenase 1 at both transcriptional and translational levels, alongside the rise in Nrf2. Model/species: RAW 264.7 murine macrophages Tissue/system: Heme oxygenase 1 expression Exposure: (+)-Lariciresinol Route: In vitro Duration: Not stated here Limits: The abstract reports the rise in HO-1 as corresponding to the rise in Nrf2; the causal test by Nrf2 inhibition is described in the full text and was not read here. Primary reference: Antioxidant efficacy and the upregulation of Nrf2-mediated HO-1 expression by (+)-lariciresinol, a lignan isolated from Rubia philippinensis, through the activation of p38. (2017). https://pubmed.ncbi.nlm.nih.gov/28378774/ DOI: 10.1038/srep46035 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_access

Primary abstract

experimental_model

Human endothelial-cell signaling and reporter assays.

limitations

These measurements do not show direct astaxanthin binding to KEAP1 or a particular ERK isoform.

nutrient_topic

Astaxanthin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Astaxanthin

plain_language

Cells switched on a transcriptional defense program.

primary_references

Astaxanthin Induces the Nrf2/HO-1 Antioxidant Pathway in Human Umbilical Vein Endothelial Cells by Generating Trace Amounts of ROS. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29381356/ · DOI 10.1021/acs.jafc.7b05493

Astaxanthin: transport, membrane chemistry, signaling and nutrient interactions (2026-09-19) · lines 222–228

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human endothelial-cell signaling and reporter assays. · source_derived_draft · unverified_draft

## astaxanthin-nrf2-are Cells switched on a transcriptional defense program. Astaxanthin treatment increased ERK phosphorylation, Nrf2 nuclear translocation and antioxidant-response-element reporter activity in HUVECs. Model: Human endothelial-cell signaling and reporter assays. Limitations: These measurements do not show direct astaxanthin binding to KEAP1 or a particular ERK isoform. Evidence access: Primary abstract Astaxanthin Induces the Nrf2/HO-1 Antioxidant Pathway in Human Umbilical Vein Endothelial Cells by Generating Trace Amounts of ROS. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29381356/ · DOI 10.1021/acs.jafc.7b05493

evidence_span

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experimental_model

Metabolite exposure and gene/protein/redox measurements

exposure

Time- and dose-dependent apo-10-prime-lycopenoid exposure

limitations

Cell-culture metabolite results do not prove oral lycopene reaches equivalent tissue concentrations or prevents human cancer.

nutrient_topic

Lycopene research collection; topical membership is not evidence of a direct dietary effect. · Lycopene

organism

Human BEAS-2B bronchial epithelial cells

plain_language

A defined breakdown product activated the Nrf2-associated response.

primary_references

[lycopene-p18566994] Enzymatic metabolites of lycopene induce Nrf2-mediated expression of phase II detoxifying/antioxidant enzymes in human bronchial epithelial cells. (2008). https://pubmed.ncbi.nlm.nih.gov/18566994/ DOI: 10.1002/ijc.23696

tissue_or_cell_type

Nucleus, antioxidant enzymes and intracellular glutathione

Lycopene: absorption, metabolism, nutrient connections and human outcomes (2026-09-17) · lines 494–505

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Metabolite exposure and gene/protein/redox measurements · source_derived_draft · unverified_draft

### lycopene-apo-nrf2 Apo-10-prime-lycopenoic acid increased nuclear Nrf2 accumulation in BEAS-2B cells. Condition category: normal nutrient_topic: Lycopene research collection; topical membership is not evidence of a direct dietary effect. plain_language: A defined breakdown product activated the Nrf2-associated response. organism: Human BEAS-2B bronchial epithelial cells tissue_or_cell_type: Nucleus, antioxidant enzymes and intracellular glutathione experimental_model: Metabolite exposure and gene/protein/redox measurements limitations: Cell-culture metabolite results do not prove oral lycopene reaches equivalent tissue concentrations or prevents human cancer. exposure: Time- and dose-dependent apo-10-prime-lycopenoid exposure evidence_span: {"source_cache": "artifacts/lycopene-research/18566994.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e34a21bb159c3e48372fd5cb104bfa50572903a5ef168b10100976a718b7b534", "start_char": 0, "end_char": 1416, "text_sha256": "e34a21bb159c3e48372fd5cb104bfa50572903a5ef168b10100976a718b7b534"} [lycopene-p18566994] Enzymatic metabolites of lycopene induce Nrf2-mediated expression of phase II detoxifying/antioxidant enzymes in human bronchial epithelial cells. (2008). https://pubmed.ncbi.nlm.nih.gov/18566994/ DOI: 10.1002/ijc.23696

evidence_span

{"source_cache": "artifacts/lycopene-research/15657364.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a25b93d6074a1e560bf1e163aa70c511e99199b9bb62ccdffdbe70e51fcc7c32", "start_char": 0, "end_char": 1890, "text_sha256": "a25b93d6074a1e560bf1e163aa70c511e99199b9bb62ccdffdbe70e51fcc7c32"}

experimental_model

Reporter, expression and dominant-negative transcription-factor experiments

exposure

Lycopene and ethanolic derivative extract

limitations

Unidentified derivative extract was active; direct binding of intact lycopene to KEAP1 was not established.

nutrient_topic

Lycopene research collection; topical membership is not evidence of a direct dietary effect. · Lycopene

organism

Human cancer cell cultures

plain_language

The transcription factor moved toward the compartment where it can affect genes.

primary_references

[lycopene-p15657364] Carotenoids activate the antioxidant response element transcription system. (2005). https://pubmed.ncbi.nlm.nih.gov/15657364/ DOI: 10.1158/1535-7163.177.4.1

tissue_or_cell_type

ARE transcription and phase II enzyme expression

Lycopene: absorption, metabolism, nutrient connections and human outcomes (2026-09-17) · lines 455–466

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reporter, expression and dominant-negative transcription-factor experiments · source_derived_draft · unverified_draft

### lycopene-nrf2-location Carotenoid treatment promoted Nrf2 nuclear translocation, including colocalization with PML nuclear bodies. Condition category: normal nutrient_topic: Lycopene research collection; topical membership is not evidence of a direct dietary effect. plain_language: The transcription factor moved toward the compartment where it can affect genes. organism: Human cancer cell cultures tissue_or_cell_type: ARE transcription and phase II enzyme expression experimental_model: Reporter, expression and dominant-negative transcription-factor experiments limitations: Unidentified derivative extract was active; direct binding of intact lycopene to KEAP1 was not established. exposure: Lycopene and ethanolic derivative extract evidence_span: {"source_cache": "artifacts/lycopene-research/15657364.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a25b93d6074a1e560bf1e163aa70c511e99199b9bb62ccdffdbe70e51fcc7c32", "start_char": 0, "end_char": 1890, "text_sha256": "a25b93d6074a1e560bf1e163aa70c511e99199b9bb62ccdffdbe70e51fcc7c32"} [lycopene-p15657364] Carotenoids activate the antioxidant response element transcription system. (2005). https://pubmed.ncbi.nlm.nih.gov/15657364/ DOI: 10.1158/1535-7163.177.4.1

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/lycopene-research/15657364.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a25b93d6074a1e560bf1e163aa70c511e99199b9bb62ccdffdbe70e51fcc7c32", "start_char": 0, "end_char": 1890, "text_sha256": "a25b93d6074a1e560bf1e163aa70c511e99199b9bb62ccdffdbe70e51fcc7c32"}

experimental_model

Reporter, expression and dominant-negative transcription-factor experiments

exposure

Lycopene and ethanolic derivative extract

limitations

Unidentified derivative extract was active; direct binding of intact lycopene to KEAP1 was not established.

nutrient_topic

Lycopene research collection; topical membership is not evidence of a direct dietary effect. · Lycopene

organism

Human cancer cell cultures

plain_language

A signaling compound cannot produce this response when the experimental gene-control machinery is blocked.

primary_references

[lycopene-p15657364] Carotenoids activate the antioxidant response element transcription system. (2005). https://pubmed.ncbi.nlm.nih.gov/15657364/ DOI: 10.1158/1535-7163.177.4.1

tissue_or_cell_type

ARE transcription and phase II enzyme expression

trigger_kind

machinery_impairment Imported condition classification; unverified.

Lycopene: absorption, metabolism, nutrient connections and human outcomes (2026-09-17) · lines 481–492

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reporter, expression and dominant-negative transcription-factor experiments · source_derived_draft · unverified_draft

### lycopene-nrf2-required Dominant-negative Nrf2 abolished the carotenoid-induced rise in phase II enzymes. Condition category: machinery_impairment nutrient_topic: Lycopene research collection; topical membership is not evidence of a direct dietary effect. plain_language: A signaling compound cannot produce this response when the experimental gene-control machinery is blocked. organism: Human cancer cell cultures tissue_or_cell_type: ARE transcription and phase II enzyme expression experimental_model: Reporter, expression and dominant-negative transcription-factor experiments limitations: Unidentified derivative extract was active; direct binding of intact lycopene to KEAP1 was not established. exposure: Lycopene and ethanolic derivative extract evidence_span: {"source_cache": "artifacts/lycopene-research/15657364.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a25b93d6074a1e560bf1e163aa70c511e99199b9bb62ccdffdbe70e51fcc7c32", "start_char": 0, "end_char": 1890, "text_sha256": "a25b93d6074a1e560bf1e163aa70c511e99199b9bb62ccdffdbe70e51fcc7c32"} [lycopene-p15657364] Carotenoids activate the antioxidant response element transcription system. (2005). https://pubmed.ncbi.nlm.nih.gov/15657364/ DOI: 10.1158/1535-7163.177.4.1

dose

Betanin 2, 10 and 20 micromolar

duration

Not specified in accessed primary abstract

evidence_access

Primary PubMed abstract; detailed exposure for PMID 23931157 additionally checked in publisher results. No uninspected full text is claimed.

evidence_scope

literature_reviewed; source-derived curation, not universally established human effects

experimental_model

Human THLE-2 non-tumour liver and HepG2 hepatoma cell lines

limitations

Responses differed by cell line. Nuclear translocation is not proof of universal transcriptional activation; kinase association does not prove direct binding. Glutathione is the shared GST substrate; this study does not show betanin raises glutathione synthesis or reverses deficiency.

nutrient_topic

Betalains collection; each molecular form, species, exposure and preparation remains explicit. · Betalains

organism

Human THLE-2 non-tumour liver and HepG2 hepatoma cell lines

plain_language

Betanin increased GSTP transcript and protein abundance in THLE-2 cells.

primary_references

Betanin, a beetroot component, induces nuclear factor erythroid-2-related factor 2-mediated expression of detoxifying/antioxidant enzymes in human liver cell lines. (2013). https://pubmed.ncbi.nlm.nih.gov/23769299/ DOI: 10.1017/S0007114513001645

route

In vitro incubation

tissue

Liver-derived cells; cytosol and nucleus

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 237–245

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Human THLE-2 non-tumour liver and HepG2 hepatoma cell lines · source_derived_draft · unverified_draft

## betalains-gstp-expression Betanin increased GSTP transcript and protein abundance in THLE-2 cells. Model/species: Human THLE-2 non-tumour liver and HepG2 hepatoma cell lines Tissue: Liver-derived cells; cytosol and nucleus Exposure: Betanin 2, 10 and 20 micromolar Route: In vitro incubation Duration: Not specified in accessed primary abstract Limits: Responses differed by cell line. Nuclear translocation is not proof of universal transcriptional activation; kinase association does not prove direct binding. Glutathione is the shared GST substrate; this study does not show betanin raises glutathione synthesis or reverses deficiency. Primary reference: Betanin, a beetroot component, induces nuclear factor erythroid-2-related factor 2-mediated expression of detoxifying/antioxidant enzymes in human liver cell lines. (2013). https://pubmed.ncbi.nlm.nih.gov/23769299/ DOI: 10.1017/S0007114513001645

dose

Betanin 2, 10 and 20 micromolar

duration

Not specified in accessed primary abstract

evidence_access

Primary PubMed abstract; detailed exposure for PMID 23931157 additionally checked in publisher results. No uninspected full text is claimed.

evidence_scope

literature_reviewed; source-derived curation, not universally established human effects

experimental_model

Human THLE-2 non-tumour liver and HepG2 hepatoma cell lines

limitations

Responses differed by cell line. Nuclear translocation is not proof of universal transcriptional activation; kinase association does not prove direct binding.

nutrient_topic

Betalains collection; each molecular form, species, exposure and preparation remains explicit. · Betalains

organism

Human THLE-2 non-tumour liver and HepG2 hepatoma cell lines

plain_language

Betanin increased NQO1 transcript and protein abundance in THLE-2 cells.

primary_references

Betanin, a beetroot component, induces nuclear factor erythroid-2-related factor 2-mediated expression of detoxifying/antioxidant enzymes in human liver cell lines. (2013). https://pubmed.ncbi.nlm.nih.gov/23769299/ DOI: 10.1017/S0007114513001645

route

In vitro incubation

tissue

Liver-derived cells; cytosol and nucleus

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 227–235

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Human THLE-2 non-tumour liver and HepG2 hepatoma cell lines · source_derived_draft · unverified_draft

## betalains-nqo1-expression Betanin increased NQO1 transcript and protein abundance in THLE-2 cells. Model/species: Human THLE-2 non-tumour liver and HepG2 hepatoma cell lines Tissue: Liver-derived cells; cytosol and nucleus Exposure: Betanin 2, 10 and 20 micromolar Route: In vitro incubation Duration: Not specified in accessed primary abstract Limits: Responses differed by cell line. Nuclear translocation is not proof of universal transcriptional activation; kinase association does not prove direct binding. Primary reference: Betanin, a beetroot component, induces nuclear factor erythroid-2-related factor 2-mediated expression of detoxifying/antioxidant enzymes in human liver cell lines. (2013). https://pubmed.ncbi.nlm.nih.gov/23769299/ DOI: 10.1017/S0007114513001645

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/zeaxanthin-research/24810054.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f185c805dd5d825445cb40e547b794fbc595388aff6e2d29ac81c2eab8b8348", "start_char": 5813, "end_char": 15716, "text_sha256": "89e6abf1967c10b359cb62d935d5b839cf53acf42576d9db3d463bff9f474e38"}

experimental_model

Cell challenge with siRNA and pathway inhibitors

exposure

Zeaxanthin commonly 10 micromolar for 24 h; 300 micromolar t-BHP challenge for 6 h; study-specific inhibitors

limitations

Pharmacological cell exposures are not dietary concentrations. PI3K/Akt inhibitor evidence is not direct zeaxanthin binding to a kinase. Liposome GSTP1 protection and this cellular GSH-dependent response are different mechanisms.

nutrient_topic

Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin

organism

Human ARPE-19 cell line

plain_language

Adding pigment could not fully replace the missing regulatory machinery.

primary_references

[zeaxanthin-p24810054] Zeaxanthin induces Nrf2-mediated phase II enzymes in protection of cell death. (2014). https://pubmed.ncbi.nlm.nih.gov/24810054/ DOI: 10.1038/cddis.2014.190

tissue_or_cell_type

Retinal pigment epithelial model

trigger_kind

machinery_impairment Imported condition classification; unverified.

Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 444–455

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell challenge with siRNA and pathway inhibitors · source_derived_draft · unverified_draft

### zeaxanthin-nrf2-failure Nrf2 knockdown suppressed zeaxanthin-induced glutathione accumulation. Condition category: machinery_impairment nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Adding pigment could not fully replace the missing regulatory machinery. organism: Human ARPE-19 cell line tissue_or_cell_type: Retinal pigment epithelial model experimental_model: Cell challenge with siRNA and pathway inhibitors limitations: Pharmacological cell exposures are not dietary concentrations. PI3K/Akt inhibitor evidence is not direct zeaxanthin binding to a kinase. Liposome GSTP1 protection and this cellular GSH-dependent response are different mechanisms. exposure: Zeaxanthin commonly 10 micromolar for 24 h; 300 micromolar t-BHP challenge for 6 h; study-specific inhibitors evidence_span: {"source_cache": "artifacts/zeaxanthin-research/24810054.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f185c805dd5d825445cb40e547b794fbc595388aff6e2d29ac81c2eab8b8348", "start_char": 5813, "end_char": 15716, "text_sha256": "89e6abf1967c10b359cb62d935d5b839cf53acf42576d9db3d463bff9f474e38"} [zeaxanthin-p24810054] Zeaxanthin induces Nrf2-mediated phase II enzymes in protection of cell death. (2014). https://pubmed.ncbi.nlm.nih.gov/24810054/ DOI: 10.1038/cddis.2014.190