Human heme oxygenase 1 / HMOX1

evidence_span

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experimental_model

Cultured human lens epithelial cells exposed to extreme hyperbaric oxygen with enzyme assays and real-time PCR

exposure

99% oxygen at 50 atmospheres for 3 hours, then normal culture for up to 11 days

limitations

Fifty atmospheres is an extreme experimental exposure far above therapy, chosen to probe which defences matter. The selenoenzyme result is the informative part; the pressure is not clinically relevant.

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 cells

plain_language

Iron freed from heme may be the signal that calls up the manganese enzyme.

primary_references

[hbot-p15642322] Thioredoxin reductase may be essential for the normal growth of hyperbaric oxygen-treated human lens epithelial cells. (2004). https://pubmed.ncbi.nlm.nih.gov/15642322/ DOI: 10.1016/j.exer.2004.07.001

tissue_or_cell_type

Lens epithelium

Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 439–450

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cultured human lens epithelial cells exposed to extreme hyperbaric oxygen with enzyme assays and real-time PCR · source_derived_draft · unverified_draft

### hbot-ho1-iron-to-mnsod The authors suggest that release of free iron from the degradation of heme by heme oxygenase-1 may have played a role in the later upregulation of the manganese dismutase. 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: Iron freed from heme may be the signal that calls up the manganese enzyme. organism: Human cells tissue_or_cell_type: Lens epithelium experimental_model: Cultured human lens epithelial cells exposed to extreme hyperbaric oxygen with enzyme assays and real-time PCR limitations: Fifty atmospheres is an extreme experimental exposure far above therapy, chosen to probe which defences matter. The selenoenzyme result is the informative part; the pressure is not clinically relevant. exposure: 99% oxygen at 50 atmospheres for 3 hours, then normal culture for up to 11 days evidence_span: {"source_cache": "artifacts/hbot-research/15642322.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e3bc035a17e4e19dd92d4fadb1a79f8e3801619dac24fb91dcf985728afaf995", "start_char": 0, "end_char": 2646, "text_sha256": "e3bc035a17e4e19dd92d4fadb1a79f8e3801619dac24fb91dcf985728afaf995"} [hbot-p15642322] Thioredoxin reductase may be essential for the normal growth of hyperbaric oxygen-treated human lens epithelial cells. (2004). https://pubmed.ncbi.nlm.nih.gov/15642322/ DOI: 10.1016/j.exer.2004.07.001

evidence_span

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experimental_model

Comet assay in lymphocytes of volunteers before and after hyperbaric oxygen, with enzyme expression measurement

exposure

100% oxygen at 2.5 ATA for three 20-minute periods

limitations

A human exposure study with a within-subject design. The iron-sequestration explanation is the authors’ inference from the pattern of protection, not a direct measurement of free iron.

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 proposed protection is locking away the iron that would otherwise turn peroxide into a more dangerous radical.

primary_references

[hbot-p11023535] Induction of heme oxygenase-1 and adaptive protection against the induction of DNA damage after hyperbaric oxygen treatment. (2000). https://pubmed.ncbi.nlm.nih.gov/11023535/ DOI: 10.1093/carcin/21.10.1795

tissue_or_cell_type

Circulating lymphocytes

Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 322–333

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Comet assay in lymphocytes of volunteers before and after hyperbaric oxygen, with enzyme expression measurement · source_derived_draft · unverified_draft

### hbot-iron-sequestration-hypothesis The authors suggest that increased sequestration of iron as a consequence of induced heme oxygenase-1 might be involved in the adaptive protection, and that induction of DNA damage is not the trigger for it. 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 proposed protection is locking away the iron that would otherwise turn peroxide into a more dangerous radical. organism: Human tissue_or_cell_type: Circulating lymphocytes experimental_model: Comet assay in lymphocytes of volunteers before and after hyperbaric oxygen, with enzyme expression measurement limitations: A human exposure study with a within-subject design. The iron-sequestration explanation is the authors’ inference from the pattern of protection, not a direct measurement of free iron. exposure: 100% oxygen at 2.5 ATA for three 20-minute periods evidence_span: {"source_cache": "artifacts/hbot-research/11023535.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "19b770dff3d327e2dd6d49180686f9823624190ab5693c28b88adcfaf703f14d", "start_char": 0, "end_char": 1576, "text_sha256": "19b770dff3d327e2dd6d49180686f9823624190ab5693c28b88adcfaf703f14d"} [hbot-p11023535] Induction of heme oxygenase-1 and adaptive protection against the induction of DNA damage after hyperbaric oxygen treatment. (2000). https://pubmed.ncbi.nlm.nih.gov/11023535/ DOI: 10.1093/carcin/21.10.1795

evidence_span

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experimental_model

Product-bound human HO-1 structure

exposure

Biliverdin-bound structure compared with heme-bound enzyme

limitations

Product release interpretation from structure; no in-vivo flux measurement.

nutrient_topic

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

organism

Human enzyme

plain_language

Breaking open heme makes its iron available for reuse.

primary_references

[iron-p15049686] Crystal structure of human heme oxygenase-1 in a complex with biliverdin. (2004). https://pubmed.ncbi.nlm.nih.gov/15049686/ DOI: 10.1021/bi035451l

tissue_or_cell_type

Purified heme oxygenase-1

Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 576–587

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Product-bound human HO-1 structure · source_derived_draft · unverified_draft

### iron-heme-oxygenase Heme oxygenase oxidatively cleaves heme to biliverdin with release of iron and carbon monoxide. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Breaking open heme makes its iron available for reuse. organism: Human enzyme tissue_or_cell_type: Purified heme oxygenase-1 experimental_model: Product-bound human HO-1 structure limitations: Product release interpretation from structure; no in-vivo flux measurement. exposure: Biliverdin-bound structure compared with heme-bound enzyme evidence_span: {"source_cache": "artifacts/iron-research/15049686.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "76bcb8ae12316350b1161f32c1633e2b5c752fcbf7e158940385b354ee3452d2", "start_char": 0, "end_char": 1167, "text_sha256": "76bcb8ae12316350b1161f32c1633e2b5c752fcbf7e158940385b354ee3452d2"} [iron-p15049686] Crystal structure of human heme oxygenase-1 in a complex with biliverdin. (2004). https://pubmed.ncbi.nlm.nih.gov/15049686/ DOI: 10.1021/bi035451l

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

Reported as the effector arm of the Nrf2 response.

organism

Human gingival fibroblasts (HGF-1)

plain_language

Nattokinase raised heme oxygenase 1 expression in the same cells.

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 554–554

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 raised heme oxygenase 1 expression in the same cells.

evidence_span

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experimental_model

Replicative culture and metabolic/gene-expression measurements

exposure

Sulforaphane treatment during serial culture

limitations

Cell-culture senescence is not human longevity; expression is not necessarily flux.

nutrient_topic

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

organism

Human MRC-5 and BJ fibroblasts

plain_language

The response includes this separately identified defense-system protein.

primary_references

[sulforaphane-p30595796] Sulforaphane Delays Fibroblast Senescence by Curbing Cellular Glucose Uptake, Increased Glycolysis, and Oxidative Damage. (2018). https://pubmed.ncbi.nlm.nih.gov/30595796/ DOI: 10.1155/2018/5642148

tissue_or_cell_type

Glucose handling, antioxidant response and senescence

Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 957–968

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Replicative culture and metabolic/gene-expression measurements · source_derived_draft · unverified_draft

### sulforaphane-hmox1-induction Sulforaphane increased HMOX1 gene expression in early-passage nonsenescent MRC-5 fibroblasts. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: The response includes this separately identified defense-system protein. organism: Human MRC-5 and BJ fibroblasts tissue_or_cell_type: Glucose handling, antioxidant response and senescence experimental_model: Replicative culture and metabolic/gene-expression measurements limitations: Cell-culture senescence is not human longevity; expression is not necessarily flux. exposure: Sulforaphane treatment during serial culture evidence_span: {"source_cache": "artifacts/sulforaphane-research/30595796.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "13f25a5ca61ca9bdf80d4b24878682c90b414a5718a73b6a5b86ff20a9673279", "start_char": 14986, "end_char": 15205, "text_sha256": "c8a5b844826129e5cff61e4e19c0eb34f04a29a8feb8ced52a567eae1585d935"} [sulforaphane-p30595796] Sulforaphane Delays Fibroblast Senescence by Curbing Cellular Glucose Uptake, Increased Glycolysis, and Oxidative Damage. (2018). https://pubmed.ncbi.nlm.nih.gov/30595796/ DOI: 10.1155/2018/5642148

evidence_span

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experimental_model

Hydrogen-peroxide challenge with pharmacological HO-1 inhibition

exposure

Mangiferin before H2O2 exposure

limitations

Cell protection is not demonstrated retinal clinical efficacy; GPx isoforms unresolved and expression is not cofactor sufficiency.

nutrient_topic

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

organism

Homo sapiens

plain_language

The heme-processing stress-response pathway was activated.

primary_references

[mangiferin-p38586992] Activation of Heme Oxygenase-1 by Mangiferin in Human Retinal Pigment Epithelial Cells Contributes to Blocking Oxidative Damage. (2024). https://pubmed.ncbi.nlm.nih.gov/38586992/ DOI: 10.4062/biomolther.2023.175

tissue_or_cell_type

ARPE-19 retinal pigment epithelial cells

Mangiferin: metabolism, signaling and nutrient connections (2026-09-17) · lines 640–651

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Hydrogen-peroxide challenge with pharmacological HO-1 inhibition · source_derived_draft · unverified_draft

### mangiferin-rpe-ho1 Mangiferin increased HO-1 expression and activity in ARPE-19 cells. Condition category: normal nutrient_topic: Mangiferin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The heme-processing stress-response pathway was activated. organism: Homo sapiens tissue_or_cell_type: ARPE-19 retinal pigment epithelial cells experimental_model: Hydrogen-peroxide challenge with pharmacological HO-1 inhibition limitations: Cell protection is not demonstrated retinal clinical efficacy; GPx isoforms unresolved and expression is not cofactor sufficiency. exposure: Mangiferin before H2O2 exposure evidence_span: {"source_cache": "artifacts/mangiferin-research/38586992.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3568135f9e3471d748a1f42c7ed136800b1cb9d017ebd9aa1522de71b71a72be", "start_char": 0, "end_char": 1792, "text_sha256": "3568135f9e3471d748a1f42c7ed136800b1cb9d017ebd9aa1522de71b71a72be"} [mangiferin-p38586992] Activation of Heme Oxygenase-1 by Mangiferin in Human Retinal Pigment Epithelial Cells Contributes to Blocking Oxidative Damage. (2024). https://pubmed.ncbi.nlm.nih.gov/38586992/ DOI: 10.4062/biomolther.2023.175

evidence_span

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experimental_model

Comet assay in lymphocytes of volunteers before and after hyperbaric oxygen, with enzyme expression measurement

exposure

100% oxygen at 2.5 ATA for three 20-minute periods

limitations

A human exposure study with a within-subject design. The iron-sequestration explanation is the authors’ inference from the pattern of protection, not a direct measurement of free iron.

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

Only one defence protein went up, and it is the one that handles heme iron.

primary_references

[hbot-p11023535] Induction of heme oxygenase-1 and adaptive protection against the induction of DNA damage after hyperbaric oxygen treatment. (2000). https://pubmed.ncbi.nlm.nih.gov/11023535/ DOI: 10.1093/carcin/21.10.1795

tissue_or_cell_type

Circulating lymphocytes

Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 309–320

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Comet assay in lymphocytes of volunteers before and after hyperbaric oxygen, with enzyme expression measurement · source_derived_draft · unverified_draft

### hbot-ho1-induction Heme oxygenase-1 levels were increased in lymphocytes 24 hours after treatment, while superoxide dismutase, catalase and the DNA repair enzymes apurinic endonuclease and DNA polymerase beta were not enhanced in expression. 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: Only one defence protein went up, and it is the one that handles heme iron. organism: Human tissue_or_cell_type: Circulating lymphocytes experimental_model: Comet assay in lymphocytes of volunteers before and after hyperbaric oxygen, with enzyme expression measurement limitations: A human exposure study with a within-subject design. The iron-sequestration explanation is the authors’ inference from the pattern of protection, not a direct measurement of free iron. exposure: 100% oxygen at 2.5 ATA for three 20-minute periods evidence_span: {"source_cache": "artifacts/hbot-research/11023535.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "19b770dff3d327e2dd6d49180686f9823624190ab5693c28b88adcfaf703f14d", "start_char": 0, "end_char": 1576, "text_sha256": "19b770dff3d327e2dd6d49180686f9823624190ab5693c28b88adcfaf703f14d"} [hbot-p11023535] Induction of heme oxygenase-1 and adaptive protection against the induction of DNA damage after hyperbaric oxygen treatment. (2000). https://pubmed.ncbi.nlm.nih.gov/11023535/ DOI: 10.1093/carcin/21.10.1795

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

The cells increased instructions for HMOX1; this does not measure the protein’s activity or a health benefit.

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 534–545

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-hmox1-transcription Boric acid increased HMOX1 mRNA at measured time points within 1–4 hours in human DU-145 cells. Condition category: normal nutrient_topic: Boron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cells increased instructions for HMOX1; this does not measure the protein’s activity or a health benefit. 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 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

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.

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

{"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"}

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

One responding enzyme handles heme turnover.

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 507–518

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-hmox1 Apo-10-prime-lycopenoic acid induced heme oxygenase-1 in bronchial epithelial cells. Condition category: normal nutrient_topic: Lycopene research collection; topical membership is not evidence of a direct dietary effect. plain_language: One responding enzyme handles heme turnover. 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/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"}

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

The aldehyde product had activity too.

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 598–609

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-lycopenal-hmox1 Apo-10-prime-lycopenal also induced HMOX1 gene expression in BEAS-2B cells. Condition category: normal nutrient_topic: Lycopene research collection; topical membership is not evidence of a direct dietary effect. plain_language: The aldehyde product had activity too. 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/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"}

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

The alcohol product had its own recorded activity.

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 585–596

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-lycopenol-hmox1 Apo-10-prime-lycopenol also induced HMOX1 gene expression in BEAS-2B cells. Condition category: normal nutrient_topic: Lycopene research collection; topical membership is not evidence of a direct dietary effect. plain_language: The alcohol product had its own recorded activity. 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

dose

Betalains 5-80 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 Caco-2 intestinal epithelial cell model

limitations

Low apparent permeability in cultured cells is not a measured human oral bioavailability fraction; findings depend on pigment and assay. Expression response in this cell model; not direct HMOX1 activation or a demonstrated increase in heme turnover.

nutrient_topic

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

organism

Human Caco-2 intestinal epithelial cell model

plain_language

Betanin increased heme oxygenase-1 in the Caco-2 comparison; the two tested betaxanthins did not share this response.

primary_references

Uptake and Immunomodulatory Properties of Betanin, Vulgaxanthin I and Indicaxanthin towards Caco-2 Intestinal Cells. (2022). https://pubmed.ncbi.nlm.nih.gov/36009345/ DOI: 10.3390/antiox11081627

route

In vitro exposure

tissue

Intestinal cells and monolayer transport

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 357–365

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Human Caco-2 intestinal epithelial cell model · source_derived_draft · unverified_draft

## betalains-caco2-hmox1 Betanin increased heme oxygenase-1 in the Caco-2 comparison; the two tested betaxanthins did not share this response. Model/species: Human Caco-2 intestinal epithelial cell model Tissue: Intestinal cells and monolayer transport Exposure: Betalains 5-80 micromolar Route: In vitro exposure Duration: Not specified in accessed primary abstract Limits: Low apparent permeability in cultured cells is not a measured human oral bioavailability fraction; findings depend on pigment and assay. Expression response in this cell model; not direct HMOX1 activation or a demonstrated increase in heme turnover. Primary reference: Uptake and Immunomodulatory Properties of Betanin, Vulgaxanthin I and Indicaxanthin towards Caco-2 Intestinal Cells. (2022). https://pubmed.ncbi.nlm.nih.gov/36009345/ DOI: 10.3390/antiox11081627

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

Another Nrf2-regulated defense enzyme increased.

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

Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 405–416

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-hmox1-expression Zeaxanthin increased HMOX1 mRNA and protein. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Another Nrf2-regulated defense enzyme increased. 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

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.

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/mangiferin-research/38586992.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3568135f9e3471d748a1f42c7ed136800b1cb9d017ebd9aa1522de71b71a72be", "start_char": 0, "end_char": 1792, "text_sha256": "3568135f9e3471d748a1f42c7ed136800b1cb9d017ebd9aa1522de71b71a72be"}

experimental_model

Hydrogen-peroxide challenge with pharmacological HO-1 inhibition

exposure

Mangiferin before H2O2 exposure

limitations

Cell protection is not demonstrated retinal clinical efficacy; GPx isoforms unresolved and expression is not cofactor sufficiency.

nutrient_topic

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

organism

Homo sapiens

plain_language

The response depended in part on available enzyme activity.

primary_references

[mangiferin-p38586992] Activation of Heme Oxygenase-1 by Mangiferin in Human Retinal Pigment Epithelial Cells Contributes to Blocking Oxidative Damage. (2024). https://pubmed.ncbi.nlm.nih.gov/38586992/ DOI: 10.4062/biomolther.2023.175

tissue_or_cell_type

ARPE-19 retinal pigment epithelial cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Mangiferin: metabolism, signaling and nutrient connections (2026-09-17) · lines 653–664

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Hydrogen-peroxide challenge with pharmacological HO-1 inhibition · source_derived_draft · unverified_draft

### mangiferin-ho1-loss HO-1 inhibition attenuated the protective effect of mangiferin against H2O2 injury. Condition category: machinery_impairment nutrient_topic: Mangiferin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The response depended in part on available enzyme activity. organism: Homo sapiens tissue_or_cell_type: ARPE-19 retinal pigment epithelial cells experimental_model: Hydrogen-peroxide challenge with pharmacological HO-1 inhibition limitations: Cell protection is not demonstrated retinal clinical efficacy; GPx isoforms unresolved and expression is not cofactor sufficiency. exposure: Mangiferin before H2O2 exposure evidence_span: {"source_cache": "artifacts/mangiferin-research/38586992.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3568135f9e3471d748a1f42c7ed136800b1cb9d017ebd9aa1522de71b71a72be", "start_char": 0, "end_char": 1792, "text_sha256": "3568135f9e3471d748a1f42c7ed136800b1cb9d017ebd9aa1522de71b71a72be"} [mangiferin-p38586992] Activation of Heme Oxygenase-1 by Mangiferin in Human Retinal Pigment Epithelial Cells Contributes to Blocking Oxidative Damage. (2024). https://pubmed.ncbi.nlm.nih.gov/38586992/ DOI: 10.4062/biomolther.2023.175

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/hbot-research/11751428.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d8fb2631feb55cff2514149c0935ad25230bbdc520cc82dddaec2baa4ada40f3", "start_char": 0, "end_char": 1641, "text_sha256": "d8fb2631feb55cff2514149c0935ad25230bbdc520cc82dddaec2baa4ada40f3"}

experimental_model

Isolated human lymphocytes exposed in vitro with a specific heme oxygenase-1 inhibitor

exposure

Hyperbaric oxygen in vitro, 2 hours at 3 bar; tin-mesoporphyrin IX

limitations

An inhibitor experiment that establishes requirement in this cell system. The authors state the exact mechanism by which the enzyme protects remains to be elucidated.

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 lymphocytes and V79 cells

plain_language

Block that one enzyme and the protection disappears.

primary_references

[hbot-p11751428] Involvement of heme oxygenase-1 (HO-1) in the adaptive protection of human lymphocytes after hyperbaric oxygen (HBO) treatment. (2001). https://pubmed.ncbi.nlm.nih.gov/11751428/ DOI: 10.1093/carcin/22.12.1979

tissue_or_cell_type

Isolated lymphocytes

trigger_kind

machinery_impairment Imported condition classification; unverified.

Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 335–346

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isolated human lymphocytes exposed in vitro with a specific heme oxygenase-1 inhibitor · source_derived_draft · unverified_draft

### hbot-ho1-required Treatment with the specific heme oxygenase-1 inhibitor tin-mesoporphyrin IX led to complete abrogation of the hyperbaric-oxygen-induced adaptive protection in human lymphocytes, and the time course of induction paralleled the development of protection. Condition category: machinery_impairment 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: Block that one enzyme and the protection disappears. organism: Human lymphocytes and V79 cells tissue_or_cell_type: Isolated lymphocytes experimental_model: Isolated human lymphocytes exposed in vitro with a specific heme oxygenase-1 inhibitor limitations: An inhibitor experiment that establishes requirement in this cell system. The authors state the exact mechanism by which the enzyme protects remains to be elucidated. exposure: Hyperbaric oxygen in vitro, 2 hours at 3 bar; tin-mesoporphyrin IX evidence_span: {"source_cache": "artifacts/hbot-research/11751428.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d8fb2631feb55cff2514149c0935ad25230bbdc520cc82dddaec2baa4ada40f3", "start_char": 0, "end_char": 1641, "text_sha256": "d8fb2631feb55cff2514149c0935ad25230bbdc520cc82dddaec2baa4ada40f3"} [hbot-p11751428] Involvement of heme oxygenase-1 (HO-1) in the adaptive protection of human lymphocytes after hyperbaric oxygen (HBO) treatment. (2001). https://pubmed.ncbi.nlm.nih.gov/11751428/ DOI: 10.1093/carcin/22.12.1979

evidence_span

{"source_cache": "artifacts/hbot-research/15642322.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e3bc035a17e4e19dd92d4fadb1a79f8e3801619dac24fb91dcf985728afaf995", "start_char": 0, "end_char": 2646, "text_sha256": "e3bc035a17e4e19dd92d4fadb1a79f8e3801619dac24fb91dcf985728afaf995"}

experimental_model

Cultured human lens epithelial cells exposed to extreme hyperbaric oxygen with enzyme assays and real-time PCR

exposure

99% oxygen at 50 atmospheres for 3 hours, then normal culture for up to 11 days

limitations

Fifty atmospheres is an extreme experimental exposure far above therapy, chosen to probe which defences matter. The selenoenzyme result is the informative part; the pressure is not clinically relevant.

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 cells

plain_language

The cell rebuilt exactly three proteins: the heme enzyme, the manganese enzyme and the selenium enzyme.

primary_references

[hbot-p15642322] Thioredoxin reductase may be essential for the normal growth of hyperbaric oxygen-treated human lens epithelial cells. (2004). https://pubmed.ncbi.nlm.nih.gov/15642322/ DOI: 10.1016/j.exer.2004.07.001

tissue_or_cell_type

Lens epithelium

Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 426–437

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cultured human lens epithelial cells exposed to extreme hyperbaric oxygen with enzyme assays and real-time PCR · source_derived_draft · unverified_draft

### hbot-trxr-mrna-response Messenger RNA for heme oxygenase-1, manganese superoxide dismutase and cytoplasmic thioredoxin reductase 1 rose three- to six-fold nine hours after exposure, with heme oxygenase-1 rising a few hours before manganese superoxide dismutase, while catalase, copper-zinc superoxide dismutase, glutathione reductase, glutathione peroxidase and thioredoxin did not change. 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 cell rebuilt exactly three proteins: the heme enzyme, the manganese enzyme and the selenium enzyme. organism: Human cells tissue_or_cell_type: Lens epithelium experimental_model: Cultured human lens epithelial cells exposed to extreme hyperbaric oxygen with enzyme assays and real-time PCR limitations: Fifty atmospheres is an extreme experimental exposure far above therapy, chosen to probe which defences matter. The selenoenzyme result is the informative part; the pressure is not clinically relevant. exposure: 99% oxygen at 50 atmospheres for 3 hours, then normal culture for up to 11 days evidence_span: {"source_cache": "artifacts/hbot-research/15642322.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e3bc035a17e4e19dd92d4fadb1a79f8e3801619dac24fb91dcf985728afaf995", "start_char": 0, "end_char": 2646, "text_sha256": "e3bc035a17e4e19dd92d4fadb1a79f8e3801619dac24fb91dcf985728afaf995"} [hbot-p15642322] Thioredoxin reductase may be essential for the normal growth of hyperbaric oxygen-treated human lens epithelial cells. (2004). https://pubmed.ncbi.nlm.nih.gov/15642322/ DOI: 10.1016/j.exer.2004.07.001

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

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"}