Component

Human toll-like receptor 4 / TLR4

Human toll-like receptor 4 / TLR4. Species, exposure and limitations are retained in each linked claim.

8 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 it acts on

  1. TLR4 silencing reduced cucurbitacin B-induced pyroptosis and associated mitochondrial ROS and calcium signals in human NSCLC cells.

    Human toll-like receptor 4 / TLR4 → Human NSCLC pyroptotic response during cucurbitacin B exposure source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Human NSCLC loss-of-function experiments.
    limitations
    The accessed abstract does not establish the calcium store or channel; oral calcium depletion is not implied.
    nutrient_topic
    Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
    plain_language
    Removing the receptor weakened the tested death pathway.
    primary_references
    Cucurbitacin B inhibits non-small cell lung cancer in vivo and in vitro by triggering TLR4/NLRP3/GSDMD-dependent pyroptosis. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34217831/ · DOI 10.1016/j.phrs.2021.105748
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 292–298

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human NSCLC loss-of-function experiments. · source_derived_draft · unverified_draft

    ## cucurbitacin-b-tlr4-loss Removing the receptor weakened the tested death pathway. TLR4 silencing reduced cucurbitacin B-induced pyroptosis and associated mitochondrial ROS and calcium signals in human NSCLC cells. Model: Human NSCLC loss-of-function experiments. Limitations: The accessed abstract does not establish the calcium store or channel; oral calcium depletion is not implied. Evidence access: Primary abstract Cucurbitacin B inhibits non-small cell lung cancer in vivo and in vitro by triggering TLR4/NLRP3/GSDMD-dependent pyroptosis. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34217831/ · DOI 10.1016/j.phrs.2021.105748
    Complete structured claim and evidence

What acts on it

  1. Docking and CETSA supported an interaction between cucurbitacin B and TLR4 in the NSCLC study.

    Cucurbitacin B → Human toll-like receptor 4 / TLR4 source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human NSCLC cell experiments with animal tumor models in the same paper.
    limitations
    No purified affinity or exclusive target assignment follows from docking plus CETSA.
    nutrient_topic
    Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
    plain_language
    Another proposed target was tested in cells.
    primary_references
    Cucurbitacin B inhibits non-small cell lung cancer in vivo and in vitro by triggering TLR4/NLRP3/GSDMD-dependent pyroptosis. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34217831/ · DOI 10.1016/j.phrs.2021.105748

    Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 284–290

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human NSCLC cell experiments with animal tumor models in the same paper. · source_derived_draft · unverified_draft

    ## cucurbitacin-b-tlr4-engagement Another proposed target was tested in cells. Docking and CETSA supported an interaction between cucurbitacin B and TLR4 in the NSCLC study. Model: Human NSCLC cell experiments with animal tumor models in the same paper. Limitations: No purified affinity or exclusive target assignment follows from docking plus CETSA. Evidence access: Primary abstract Cucurbitacin B inhibits non-small cell lung cancer in vivo and in vitro by triggering TLR4/NLRP3/GSDMD-dependent pyroptosis. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34217831/ · DOI 10.1016/j.phrs.2021.105748
    Complete structured claim and evidence

  2. Receptor mapping found sulforaphane adducts at TLR4 C246 and C609 under non-reducing conditions.

    Sulforaphane / SFN, stereochemistry specified per study → Human toll-like receptor 4 / TLR4 source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/sulforaphane-research/25284333.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0a293f12863f5cfc2d57d74f4acee8c62700e2744a5900643bc23eca85c62be5", "start_char": 0, "end_char": 1494, "text_sha256": "0a293f12863f5cfc2d57d74f4acee8c62700e2744a5900643bc23eca85c62be5"}
    experimental_model
    Recombinant receptor mapping, human cell exposure and ex vivo challenge
    exposure
    Sulforaphane under non-reducing conditions; LPS challenge after ITC exposure
    limitations
    Covalent mapping does not establish the sole cause of cytokine effects; not a chronic-disease outcome trial.
    nutrient_topic
    Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study
    organism
    Human TLR4, THP-1 monocytes and donor PBMCs
    plain_language
    The compound can interact with an inflammatory sensor as well as KEAP1.
    primary_references
    [sulforaphane-p25284333] Suppression of LPS-induced transcription and cytokine secretion by the dietary isothiocyanate sulforaphane. (2014). https://pubmed.ncbi.nlm.nih.gov/25284333/ DOI: 10.1002/mnfr.201400550
    tissue_or_cell_type
    LPS recognition and cytokine secretion

    Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 671–682

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant receptor mapping, human cell exposure and ex vivo challenge · source_derived_draft · unverified_draft

    ### sulforaphane-tlr4-adduct Receptor mapping found sulforaphane adducts at TLR4 C246 and C609 under non-reducing conditions. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: The compound can interact with an inflammatory sensor as well as KEAP1. organism: Human TLR4, THP-1 monocytes and donor PBMCs tissue_or_cell_type: LPS recognition and cytokine secretion experimental_model: Recombinant receptor mapping, human cell exposure and ex vivo challenge limitations: Covalent mapping does not establish the sole cause of cytokine effects; not a chronic-disease outcome trial. exposure: Sulforaphane under non-reducing conditions; LPS challenge after ITC exposure evidence_span: {"source_cache": "artifacts/sulforaphane-research/25284333.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0a293f12863f5cfc2d57d74f4acee8c62700e2744a5900643bc23eca85c62be5", "start_char": 0, "end_char": 1494, "text_sha256": "0a293f12863f5cfc2d57d74f4acee8c62700e2744a5900643bc23eca85c62be5"} [sulforaphane-p25284333] Suppression of LPS-induced transcription and cytokine secretion by the dietary isothiocyanate sulforaphane. (2014). https://pubmed.ncbi.nlm.nih.gov/25284333/ DOI: 10.1002/mnfr.201400550
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Maximum plasma concentrations for glucan phosphate occurred at 4 hours while laminarin and scleroglucan showed two plasma peaks between 0.5 and 12 hours, at 24 hours 27 plus or minus 3% of the glucan phosphate and 20 plus or minus 7% of the laminarin remained in the serum, following oral administration glucans were bound and internalized by intestinal epithelial cells and gut-associated lymphoid tissue cells with internalization by intestinal epithelial cells not being Dectin-dependent, gut-associated lymphoid tissue expression of Dectin-1 and Toll-like receptor 2 but not Toll-like receptor 4 increased, oral glucan increased systemic levels of interleukin-12 by 151%, and oral glucan administration also increased survival in mice challenged with Staphylococcus aureus or Candida albicans.

    Glucan phosphate → Serum beta-glucan concentration after oral dosing source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/glucan-research/15976018.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "19df013d426cc48180a1bc6bb1e1e359c1d8b1f923cc97be369f5ad9116c3b18", "start_char": 0, "end_char": 1617, "text_sha256": "19df013d426cc48180a1bc6bb1e1e359c1d8b1f923cc97be369f5ad9116c3b18"}
    experimental_model
    Oral pharmacokinetics of three water-soluble glucans in rats, with uptake, receptor expression and infectious challenge in mice
    exposure
    Glucan phosphate, laminarin and scleroglucan at 1 milligram per kilogram orally in rats, and 1 milligram orally in mice
    limitations
    Rodent pharmacokinetics and rodent challenge models. The reported figure for glucan phosphate at 24 hours is a percentage remaining in serum whose denominator the abstract does not state, so it is not read here as a fraction of the swallowed dose.
    nutrient_topic
    Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. · Beta-glucan
    organism
    Rat and mouse
    plain_language
    In rodents the swallowed sugar does cross into the circulation, is taken up by the gut immune tissue, and leaves the animals better able to survive an infection.
    primary_references
    [bg-p15976018] Oral delivery and gastrointestinal absorption of soluble glucans stimulate increased resistance to infectious challenge. (2005). https://pubmed.ncbi.nlm.nih.gov/15976018/ DOI: 10.1124/jpet.105.085415
    tissue_or_cell_type
    Plasma, intestinal epithelium and gut-associated lymphoid tissue

    Beta-glucan: a structural family rather than an agent, what decides whether a bound glucan actually signals, the complement route that a cereal and a yeast preparation share, and the unequal human evidence behind each (2026-09-22) · lines 372–383

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oral pharmacokinetics of three water-soluble glucans in rats, with uptake, receptor expression and infectious challenge in mice · source_derived_draft · unverified_draft

    ### bg-oral-glucan-does-reach-the-blood Maximum plasma concentrations for glucan phosphate occurred at 4 hours while laminarin and scleroglucan showed two plasma peaks between 0.5 and 12 hours, at 24 hours 27 plus or minus 3% of the glucan phosphate and 20 plus or minus 7% of the laminarin remained in the serum, following oral administration glucans were bound and internalized by intestinal epithelial cells and gut-associated lymphoid tissue cells with internalization by intestinal epithelial cells not being Dectin-dependent, gut-associated lymphoid tissue expression of Dectin-1 and Toll-like receptor 2 but not Toll-like receptor 4 increased, oral glucan increased systemic levels of interleukin-12 by 151%, and oral glucan administration also increased survival in mice challenged with Staphylococcus aureus or Candida albicans. Condition category: normal nutrient_topic: Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. plain_language: In rodents the swallowed sugar does cross into the circulation, is taken up by the gut immune tissue, and leaves the animals better able to survive an infection. organism: Rat and mouse tissue_or_cell_type: Plasma, intestinal epithelium and gut-associated lymphoid tissue experimental_model: Oral pharmacokinetics of three water-soluble glucans in rats, with uptake, receptor expression and infectious challenge in mice limitations: Rodent pharmacokinetics and rodent challenge models. The reported figure for glucan phosphate at 24 hours is a percentage remaining in serum whose denominator the abstract does not state, so it is not read here as a fraction of the swallowed dose. exposure: Glucan phosphate, laminarin and scleroglucan at 1 milligram per kilogram orally in rats, and 1 milligram orally in mice evidence_span: {"source_cache": "artifacts/glucan-research/15976018.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "19df013d426cc48180a1bc6bb1e1e359c1d8b1f923cc97be369f5ad9116c3b18", "start_char": 0, "end_char": 1617, "text_sha256": "19df013d426cc48180a1bc6bb1e1e359c1d8b1f923cc97be369f5ad9116c3b18"} [bg-p15976018] Oral delivery and gastrointestinal absorption of soluble glucans stimulate increased resistance to infectious challenge. (2005). https://pubmed.ncbi.nlm.nih.gov/15976018/ DOI: 10.1124/jpet.105.085415
    Complete structured claim and evidence

  2. Cucurbitacin B exposure was associated with the TLR4/mitochondrial-ROS/NLRP3 route and gasdermin D cleavage in the NSCLC pyroptosis experiments.

    Cucurbitacin B → Human NSCLC pyroptotic response during cucurbitacin B exposure source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human NSCLC cells; mouse tumor experiments provide a separate translational level.
    limitations
    Do not merge all tumor-cell death into one obligatory linear chain.
    nutrient_topic
    Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
    plain_language
    Inflammatory membrane rupture is separate from ferroptotic lipid damage.
    primary_references
    Cucurbitacin B inhibits non-small cell lung cancer in vivo and in vitro by triggering TLR4/NLRP3/GSDMD-dependent pyroptosis. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34217831/ · DOI 10.1016/j.phrs.2021.105748

    Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 300–306

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human NSCLC cells; mouse tumor experiments provide a separate translational level. · source_derived_draft · unverified_draft

    ## cucurbitacin-b-pyroptosis-route Inflammatory membrane rupture is separate from ferroptotic lipid damage. Cucurbitacin B exposure was associated with the TLR4/mitochondrial-ROS/NLRP3 route and gasdermin D cleavage in the NSCLC pyroptosis experiments. Model: Human NSCLC cells; mouse tumor experiments provide a separate translational level. Limitations: Do not merge all tumor-cell death into one obligatory linear chain. Evidence access: Primary abstract Cucurbitacin B inhibits non-small cell lung cancer in vivo and in vitro by triggering TLR4/NLRP3/GSDMD-dependent pyroptosis. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34217831/ · DOI 10.1016/j.phrs.2021.105748
    Complete structured claim and evidence

  3. Sulforaphane suppressed LPS-induced cytokine secretion in THP-1 cells and human PBMC experiments.

    Sulforaphane / SFN, stereochemistry specified per study → LPS-induced cytokine release in human monocytes or PBMCs source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/sulforaphane-research/25284333.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0a293f12863f5cfc2d57d74f4acee8c62700e2744a5900643bc23eca85c62be5", "start_char": 0, "end_char": 1494, "text_sha256": "0a293f12863f5cfc2d57d74f4acee8c62700e2744a5900643bc23eca85c62be5"}
    experimental_model
    Recombinant receptor mapping, human cell exposure and ex vivo challenge
    exposure
    Sulforaphane under non-reducing conditions; LPS challenge after ITC exposure
    limitations
    Covalent mapping does not establish the sole cause of cytokine effects; not a chronic-disease outcome trial.
    nutrient_topic
    Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study
    organism
    Human TLR4, THP-1 monocytes and donor PBMCs
    plain_language
    An inflammatory challenge produced a smaller response in these systems.
    primary_references
    [sulforaphane-p25284333] Suppression of LPS-induced transcription and cytokine secretion by the dietary isothiocyanate sulforaphane. (2014). https://pubmed.ncbi.nlm.nih.gov/25284333/ DOI: 10.1002/mnfr.201400550
    tissue_or_cell_type
    LPS recognition and cytokine secretion

    Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 684–695

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant receptor mapping, human cell exposure and ex vivo challenge · source_derived_draft · unverified_draft

    ### sulforaphane-lps-response Sulforaphane suppressed LPS-induced cytokine secretion in THP-1 cells and human PBMC experiments. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: An inflammatory challenge produced a smaller response in these systems. organism: Human TLR4, THP-1 monocytes and donor PBMCs tissue_or_cell_type: LPS recognition and cytokine secretion experimental_model: Recombinant receptor mapping, human cell exposure and ex vivo challenge limitations: Covalent mapping does not establish the sole cause of cytokine effects; not a chronic-disease outcome trial. exposure: Sulforaphane under non-reducing conditions; LPS challenge after ITC exposure evidence_span: {"source_cache": "artifacts/sulforaphane-research/25284333.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0a293f12863f5cfc2d57d74f4acee8c62700e2744a5900643bc23eca85c62be5", "start_char": 0, "end_char": 1494, "text_sha256": "0a293f12863f5cfc2d57d74f4acee8c62700e2744a5900643bc23eca85c62be5"} [sulforaphane-p25284333] Suppression of LPS-induced transcription and cytokine secretion by the dietary isothiocyanate sulforaphane. (2014). https://pubmed.ncbi.nlm.nih.gov/25284333/ DOI: 10.1002/mnfr.201400550
    Complete structured claim and evidence

  4. In unstimulated THP-1 cells, stevioside induced TNF, IL-1beta and nitric oxide release; anti-TLR4 antibody partially neutralized TNF release.

    Stevioside → Human unstimulated THP-1 cytokine release source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human THP-1 cells; antibody perturbation.
    limitations
    This is an explained stimulus difference, not a contradiction or proof of a clinical immune benefit.
    nutrient_topic
    Stevia collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Stevia
    plain_language
    The same compound can stimulate resting cells while suppressing an already stimulated response.
    primary_references
    Anti-Inflammatory and Immunomodulatory Activities of Stevioside and Its Metabolite Steviol on THP-1 Cells. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16448183/ · DOI 10.1021/jf0523465

    Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 330–336

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human THP-1 cells; antibody perturbation. · source_derived_draft · unverified_draft

    ## stevia-immune-resting The same compound can stimulate resting cells while suppressing an already stimulated response. In unstimulated THP-1 cells, stevioside induced TNF, IL-1beta and nitric oxide release; anti-TLR4 antibody partially neutralized TNF release. Model: Human THP-1 cells; antibody perturbation. Limitations: This is an explained stimulus difference, not a contradiction or proof of a clinical immune benefit. Evidence access: Primary abstract Anti-Inflammatory and Immunomodulatory Activities of Stevioside and Its Metabolite Steviol on THP-1 Cells. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16448183/ · DOI 10.1021/jf0523465
    Complete structured claim and evidence

  5. Endotoxaemia accompanied the permeability defect and differed across stages of alcohol-induced liver disease.

    Circulating endotoxin concentration → Alcoholic liver injury source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/alcohol-research/10845660.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0342f8e351dde29e075eaf2d1920f26d1e8ef9d9a704947dc6c08f6f5fde846d", "start_char": 0, "end_char": 1618, "text_sha256": "0342f8e351dde29e075eaf2d1920f26d1e8ef9d9a704947dc6c08f6f5fde846d"}
    experimental_model
    Intestinal permeability and endotoxin measurement across stages of alcohol-induced liver disease
    exposure
    Chronic alcohol abuse, staged by liver disease severity
    limitations
    Human observational staging. It shows permeability tracks disease stage; it cannot establish which came first.
    nutrient_topic
    Alcohol research collection; topical membership is not evidence of a direct clinical effect, and ethanol is recorded separately from the acetaldehyde it becomes. · Ethanol
    organism
    Human
    plain_language
    The leak and the liver damage travel together.
    primary_references
    [alcohol-p10845660] Increased intestinal permeability to macromolecules and endotoxemia in patients with chronic alcohol abuse in different stages of alcohol-induced liver disease. (2000). https://pubmed.ncbi.nlm.nih.gov/10845660/ DOI: 10.1016/s0168-8278(00)80242-1
    tissue_or_cell_type
    Intestine and blood

    Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 475–486

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Intestinal permeability and endotoxin measurement across stages of alcohol-induced liver disease · source_derived_draft · unverified_draft

    ### alcohol-endotoxin-liver Endotoxaemia accompanied the permeability defect and differed across stages of alcohol-induced liver disease. Condition category: normal nutrient_topic: Alcohol research collection; topical membership is not evidence of a direct clinical effect, and ethanol is recorded separately from the acetaldehyde it becomes. plain_language: The leak and the liver damage travel together. organism: Human tissue_or_cell_type: Intestine and blood experimental_model: Intestinal permeability and endotoxin measurement across stages of alcohol-induced liver disease limitations: Human observational staging. It shows permeability tracks disease stage; it cannot establish which came first. exposure: Chronic alcohol abuse, staged by liver disease severity evidence_span: {"source_cache": "artifacts/alcohol-research/10845660.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0342f8e351dde29e075eaf2d1920f26d1e8ef9d9a704947dc6c08f6f5fde846d", "start_char": 0, "end_char": 1618, "text_sha256": "0342f8e351dde29e075eaf2d1920f26d1e8ef9d9a704947dc6c08f6f5fde846d"} [alcohol-p10845660] Increased intestinal permeability to macromolecules and endotoxemia in patients with chronic alcohol abuse in different stages of alcohol-induced liver disease. (2000). https://pubmed.ncbi.nlm.nih.gov/10845660/ DOI: 10.1016/s0168-8278(00)80242-1
    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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