Component

Rat Nrf2 / Nfe2l2

Rat Nrf2 / Nfe2l2. Species, exposure and limitations are retained in each linked claim.

6 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What acts on it

  1. Ankaflavin increased hepatic Nrf2 Ser40 phosphorylation without increasing measured Nrf2 mRNA or total protein in the rat experiment.

    Ankaflavin → Rat Nrf2 / Nfe2l2 source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Methylglyoxal-treated Wistar rats, four-week model.
    limitations
    Does not demonstrate direct binding to Nrf2 or KEAP1; effect cannot be assigned to dietary riboflavin.
    nutrient_topic
    Red yeast rice collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Red yeast rice
    plain_language
    Activation and abundance were different measured endpoints.
    primary_references
    [23022408] Ankaflavin: a natural novel PPARγ agonist upregulates Nrf2 to attenuate methylglyoxal-induced diabetes in vivo. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23022408/ · DOI 10.1016/j.freeradbiomed.2012.09.025

    Red yeast rice: constituents, mevalonate, CoQ and product-specific interactions (2026-09-20) · lines 244–250

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Methylglyoxal-treated Wistar rats, four-week model. · source_derived_draft · unverified_draft

    ## red-yeast-rice-ankaflavin-nrf2 Activation and abundance were different measured endpoints. Ankaflavin increased hepatic Nrf2 Ser40 phosphorylation without increasing measured Nrf2 mRNA or total protein in the rat experiment. Model: Methylglyoxal-treated Wistar rats, four-week model. Limitations: Does not demonstrate direct binding to Nrf2 or KEAP1; effect cannot be assigned to dietary riboflavin. Evidence access: Primary abstract [23022408] Ankaflavin: a natural novel PPARγ agonist upregulates Nrf2 to attenuate methylglyoxal-induced diabetes in vivo. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23022408/ · DOI 10.1016/j.freeradbiomed.2012.09.025
    Complete structured claim and evidence

  2. Fisetin increased SIRT1 and nuclear Nrf2-associated signaling in the rat cardiac study, with HO-1 and ferritin-heavy-chain expression changes.

    Fisetin → Rat Nrf2 / Nfe2l2 source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Rat hearts and rat H9c2 cells.
    limitations
    Expression is not direct enzyme activation or proof of every transcriptional step.
    nutrient_topic
    Fisetin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Fisetin
    plain_language
    Iron handling and antioxidant signaling were linked.
    primary_references
    Fisetin Attenuates Doxorubicin-Induced Cardiomyopathy In Vivo and In Vitro by Inhibiting Ferroptosis Through SIRT1/Nrf2 Signaling Pathway Activation. · 2021 · https://pubmed.ncbi.nlm.nih.gov/35273493/ · DOI 10.3389/fphar.2021.808480

    Fisetin: metabolism, cell-state responses and cross-nutrient mechanisms (2026-09-19) · lines 424–430

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat hearts and rat H9c2 cells. · source_derived_draft · unverified_draft

    ## fisetin-cardiac-nrf2 Iron handling and antioxidant signaling were linked. Fisetin increased SIRT1 and nuclear Nrf2-associated signaling in the rat cardiac study, with HO-1 and ferritin-heavy-chain expression changes. Model: Rat hearts and rat H9c2 cells. Limitations: Expression is not direct enzyme activation or proof of every transcriptional step. Evidence access: Primary abstract Fisetin Attenuates Doxorubicin-Induced Cardiomyopathy In Vivo and In Vitro by Inhibiting Ferroptosis Through SIRT1/Nrf2 Signaling Pathway Activation. · 2021 · https://pubmed.ncbi.nlm.nih.gov/35273493/ · DOI 10.3389/fphar.2021.808480
    Complete structured claim and evidence

  3. SAC 25 mg/kg attenuated the cisplatin-associated reduction of renal cortical Nrf2.

    S-allyl-L-cysteine / SAC → Rat Nrf2 / Nfe2l2 source_derived_draftungraded
    Experimental context and source evidence
    acting_entity
    s-allylcysteine
    dose
    SAC 25 mg/kg; cisplatin dose not retrieved
    duration
    Single SAC dose for signaling arm; timing not retrieved
    evidence_access
    Primary abstract
    experimental_comparison
    SAC with cisplatin versus cisplatin injury controls
    experimental_model
    Cisplatin-challenged renal cortex and isolated proximal/distal tubules
    interpretation_status
    Source-derived research curation; not independent primary verification
    limitations
    Renal protection does not establish preserved antitumor activity or a safe patient combination.
    nutrient_topic
    S-allylcysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · S-allyl-L-cysteine / SAC
    organism
    Rattus norvegicus
    plain_language
    A drug-injury model showed preservation of a defense regulator.
    primary_references
    [24779924] S-allylcysteine prevents cisplatin-induced nephrotoxicity and oxidative stress. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24779924/ · DOI 10.1111/jphp.12263
    route
    Administration route not specified in accessed abstract
    tissue_or_cell_type
    Cisplatin-challenged renal cortex and isolated proximal/distal tubules

    S-allylcysteine: sulfur signaling, redox responses and cross-nutrient mechanisms (2026-09-20) · lines 338–345

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cisplatin-challenged renal cortex and isolated proximal/distal tubules · source_derived_draft · unverified_draft

    ## s-allylcysteine-cisplatin-nrf2 A drug-injury model showed preservation of a defense regulator. SAC 25 mg/kg attenuated the cisplatin-associated reduction of renal cortical Nrf2. Model: Cisplatin-challenged renal cortex and isolated proximal/distal tubules Limitations: Renal protection does not establish preserved antitumor activity or a safe patient combination. Evidence access: Primary abstract [24779924] S-allylcysteine prevents cisplatin-induced nephrotoxicity and oxidative stress. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24779924/ · DOI 10.1111/jphp.12263 Structured context: {"organism": "Rattus norvegicus", "tissue_or_cell_type": "Cisplatin-challenged renal cortex and isolated proximal/distal tubules", "dose": "SAC 25 mg/kg; cisplatin dose not retrieved", "duration": "Single SAC dose for signaling arm; timing not retrieved", "route": "Administration route not specified in accessed abstract", "experimental_comparison": "SAC with cisplatin versus cisplatin injury controls", "acting_entity": "s-allylcysteine", "interpretation_status": "Source-derived research curation; not independent primary verification"}
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Ankaflavin increased hepatic GCL and HO-1 transcriptional activation; these effects persisted despite PPAR-gamma antagonist treatment.

    Ankaflavin → Rat hepatic glutamate-cysteine ligase expression in the ankaflavin study source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Wistar rat methylglyoxal model with GW9662 comparison.
    limitations
    GCL subunit-specific effects were not resolved in the accessed abstract.
    nutrient_topic
    Red yeast rice collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Red yeast rice
    plain_language
    The antioxidant-expression route was not blocked in the same way as the insulin endpoints.
    primary_references
    [23022408] Ankaflavin: a natural novel PPARγ agonist upregulates Nrf2 to attenuate methylglyoxal-induced diabetes in vivo. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23022408/ · DOI 10.1016/j.freeradbiomed.2012.09.025

    Red yeast rice: constituents, mevalonate, CoQ and product-specific interactions (2026-09-20) · lines 252–258

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Wistar rat methylglyoxal model with GW9662 comparison. · source_derived_draft · unverified_draft

    ## red-yeast-rice-ankaflavin-gcl The antioxidant-expression route was not blocked in the same way as the insulin endpoints. Ankaflavin increased hepatic GCL and HO-1 transcriptional activation; these effects persisted despite PPAR-gamma antagonist treatment. Model: Wistar rat methylglyoxal model with GW9662 comparison. Limitations: GCL subunit-specific effects were not resolved in the accessed abstract. Evidence access: Primary abstract [23022408] Ankaflavin: a natural novel PPARγ agonist upregulates Nrf2 to attenuate methylglyoxal-induced diabetes in vivo. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23022408/ · DOI 10.1016/j.freeradbiomed.2012.09.025
    Complete structured claim and evidence

  2. Injected R-lipoic acid increased nuclear Nrf2 and antioxidant-response-element binding in aged rat liver.

    Free R-alpha-lipoic acid → Rat hepatic Nrf2 nuclear accumulation source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/ala-research/14985508.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a43d83e66af102cc530c2cb2da20c79749ab5c85c815e573e9797f9fc6645d13", "start_char": 0, "end_char": 1696, "text_sha256": "a43d83e66af102cc530c2cb2da20c79749ab5c85c815e573e9797f9fc6645d13"}
    experimental_model
    Aging-rat liver biochemistry and R-lipoic-acid intervention
    exposure
    R-lipoic acid 40 mg/kg intraperitoneally; time course up to 48 hours
    limitations
    Animal injection study; changes in enzyme expression are distinct from direct radical scavenging and human clinical efficacy.
    nutrient_topic
    Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
    organism
    Rat
    plain_language
    The intervention changed a gene-regulating response, beyond any direct antioxidant reaction.
    primary_references
    [ala-p14985508] Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid. (2004). https://pubmed.ncbi.nlm.nih.gov/14985508/ DOI: 10.1073/pnas.0400282101
    tissue_or_cell_type
    Liver

    Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 845–856

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Aging-rat liver biochemistry and R-lipoic-acid intervention · source_derived_draft · unverified_draft

    ### ala-rla-nrf2-rat Injected R-lipoic acid increased nuclear Nrf2 and antioxidant-response-element binding in aged rat liver. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The intervention changed a gene-regulating response, beyond any direct antioxidant reaction. organism: Rat tissue_or_cell_type: Liver experimental_model: Aging-rat liver biochemistry and R-lipoic-acid intervention limitations: Animal injection study; changes in enzyme expression are distinct from direct radical scavenging and human clinical efficacy. exposure: R-lipoic acid 40 mg/kg intraperitoneally; time course up to 48 hours evidence_span: {"source_cache": "artifacts/ala-research/14985508.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a43d83e66af102cc530c2cb2da20c79749ab5c85c815e573e9797f9fc6645d13", "start_char": 0, "end_char": 1696, "text_sha256": "a43d83e66af102cc530c2cb2da20c79749ab5c85c815e573e9797f9fc6645d13"} [ala-p14985508] Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid. (2004). https://pubmed.ncbi.nlm.nih.gov/14985508/ DOI: 10.1073/pnas.0400282101
    Complete structured claim and evidence

  3. SIRT1 inhibition attenuated fisetin protection in doxorubicin-exposed H9c2 cells and reduced the associated GSH/GPX4 response.

    Rat sirtuin 1 / Sirt1 → Fisetin-associated protection in rat H9c2 cells source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Rat cardiac-cell pharmacological inhibition.
    limitations
    Not proof that niacin or NAD supplements enhance fisetin.
    nutrient_topic
    Fisetin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Fisetin
    plain_language
    An intact regulatory pathway was required for the full response.
    primary_references
    Fisetin Attenuates Doxorubicin-Induced Cardiomyopathy In Vivo and In Vitro by Inhibiting Ferroptosis Through SIRT1/Nrf2 Signaling Pathway Activation. · 2021 · https://pubmed.ncbi.nlm.nih.gov/35273493/ · DOI 10.3389/fphar.2021.808480
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Fisetin: metabolism, cell-state responses and cross-nutrient mechanisms (2026-09-19) · lines 432–438

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat cardiac-cell pharmacological inhibition. · source_derived_draft · unverified_draft

    ## fisetin-cardiac-sirt1-block An intact regulatory pathway was required for the full response. SIRT1 inhibition attenuated fisetin protection in doxorubicin-exposed H9c2 cells and reduced the associated GSH/GPX4 response. Model: Rat cardiac-cell pharmacological inhibition. Limitations: Not proof that niacin or NAD supplements enhance fisetin. Evidence access: Primary abstract Fisetin Attenuates Doxorubicin-Induced Cardiomyopathy In Vivo and In Vitro by Inhibiting Ferroptosis Through SIRT1/Nrf2 Signaling Pathway Activation. · 2021 · https://pubmed.ncbi.nlm.nih.gov/35273493/ · DOI 10.3389/fphar.2021.808480
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

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