NF-kappa-B signaling

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_location

Abstract; NF-kappa-B inhibitor experiment

evidence_span

ameliorated the decrease in GLT-1b

experimental_model

Newborn-rat astrocytes differentiated with dibutyryl cAMP; thiamine-free DMEM with 5% horse serum plus 10 micromolar pyrithiamine; conditioned-medium transfer and inflammatory-pathway inhibitors.

exposure

Thiamine-free medium plus pyrithiamine in cultured newborn-rat astrocytes

limitations

Pharmacological inhibition is not isoform-specific genetic proof; the accessible record does not establish efficacy in intact human brain.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Rattus norvegicus

plain_language

Suppressing the inflammatory pathway helped preserve this particular glutamate-transporter isoform.

primary_references

[jhala-2014-astrocyte-inflammatory-signaling] Thiamine deficiency results in release of soluble factors that disrupt mitochondrial membrane potential and downregulate the glutamate transporter splice-variant GLT-1b in cultured astrocytes. (2014). https://www.sciencedirect.com/science/article/abs/pii/S0006291X14006482 DOI: 10.1016/j.bbrc.2014.04.017

tissue_or_cell_type

Cultured astrocytes

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1325–1337

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Newborn-rat astrocytes differentiated with dibutyryl cAMP; thiamine-free DMEM with 5% horse serum plus 10 micromolar pyrithiamine; conditioned-medium transfer and inflammatory-pathway inhibitors. · source_derived_draft · unverified_draft

### thiamine-def-nfkb-inhibition-glt1b NF-kappa-B inhibition attenuated GLT-1b loss in astrocytes exposed to the thiamine-disruption protocol. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Suppressing the inflammatory pathway helped preserve this particular glutamate-transporter isoform. organism: Rattus norvegicus tissue_or_cell_type: Cultured astrocytes experimental_model: Newborn-rat astrocytes differentiated with dibutyryl cAMP; thiamine-free DMEM with 5% horse serum plus 10 micromolar pyrithiamine; conditioned-medium transfer and inflammatory-pathway inhibitors. limitations: Pharmacological inhibition is not isoform-specific genetic proof; the accessible record does not establish efficacy in intact human brain. evidence_location: Abstract; NF-kappa-B inhibitor experiment evidence_span: ameliorated the decrease in GLT-1b exposure: Thiamine-free medium plus pyrithiamine in cultured newborn-rat astrocytes [jhala-2014-astrocyte-inflammatory-signaling] Thiamine deficiency results in release of soluble factors that disrupt mitochondrial membrane potential and downregulate the glutamate transporter splice-variant GLT-1b in cultured astrocytes. (2014). https://www.sciencedirect.com/science/article/abs/pii/S0006291X14006482 DOI: 10.1016/j.bbrc.2014.04.017

duration

Not stated here

evidence_access

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

experimental_model

Mouse RAW264.7 macrophages

exposure

Nattokinase

limitations

Nuclear translocation is the measured step; downstream mediator output (TNF-alpha, IL-6, nitric oxide and PAI-1) is reported as following from it.

organism

Mouse RAW264.7 macrophages

plain_language

Nattokinase repressed translocation of NF-kappa-B from the cytoplasm to the nucleus in stimulated macrophages, along with MAPK activation.

primary_references

Breaking the vicious loop between inflammation, oxidative stress and coagulation, a novel anti-thrombus insight of nattokinase by inhibiting LPS-induced inflammation and oxidative stress. (2020) https://pubmed.ncbi.nlm.nih.gov/32193146/ DOI: 10.1016/j.redox.2020.101500

route

In vitro

tissue

Cultured macrophages, LPS-stimulated

Nattokinase: what the purified enzyme cleaves, what survives being eaten, and the gap between the two (2026-09-23) · lines 499–499

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 · Mouse RAW264.7 macrophages · source_derived_draft · unverified_draft

Nattokinase repressed translocation of NF-kappa-B from the cytoplasm to the nucleus in stimulated macrophages, along with MAPK activation.

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_location

Abstract; TNF-alpha neutralization experiment

evidence_span

blocked the increased NF-κB activation

experimental_model

Newborn-rat astrocytes differentiated with dibutyryl cAMP; thiamine-free DMEM with 5% horse serum plus 10 micromolar pyrithiamine; conditioned-medium transfer and inflammatory-pathway inhibitors.

exposure

Thiamine-free medium plus pyrithiamine in cultured newborn-rat astrocytes

limitations

An antibody perturbation supports TNF involvement but does not establish that TNF alone explains every conditioned-medium effect.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Rattus norvegicus

plain_language

Blocking TNF signaling interrupted an inflammatory response in the cultured cells.

primary_references

[jhala-2014-astrocyte-inflammatory-signaling] Thiamine deficiency results in release of soluble factors that disrupt mitochondrial membrane potential and downregulate the glutamate transporter splice-variant GLT-1b in cultured astrocytes. (2014). https://www.sciencedirect.com/science/article/abs/pii/S0006291X14006482 DOI: 10.1016/j.bbrc.2014.04.017

tissue_or_cell_type

Cultured astrocytes

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1311–1323

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Newborn-rat astrocytes differentiated with dibutyryl cAMP; thiamine-free DMEM with 5% horse serum plus 10 micromolar pyrithiamine; conditioned-medium transfer and inflammatory-pathway inhibitors. · source_derived_draft · unverified_draft

### thiamine-def-tnf-neutralization-nfkb A TNF-alpha-neutralizing antibody blocked the increase in NF-kappa-B activation during astrocyte thiamine-disruption experiments. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Blocking TNF signaling interrupted an inflammatory response in the cultured cells. organism: Rattus norvegicus tissue_or_cell_type: Cultured astrocytes experimental_model: Newborn-rat astrocytes differentiated with dibutyryl cAMP; thiamine-free DMEM with 5% horse serum plus 10 micromolar pyrithiamine; conditioned-medium transfer and inflammatory-pathway inhibitors. limitations: An antibody perturbation supports TNF involvement but does not establish that TNF alone explains every conditioned-medium effect. evidence_location: Abstract; TNF-alpha neutralization experiment evidence_span: blocked the increased NF-κB activation exposure: Thiamine-free medium plus pyrithiamine in cultured newborn-rat astrocytes [jhala-2014-astrocyte-inflammatory-signaling] Thiamine deficiency results in release of soluble factors that disrupt mitochondrial membrane potential and downregulate the glutamate transporter splice-variant GLT-1b in cultured astrocytes. (2014). https://www.sciencedirect.com/science/article/abs/pii/S0006291X14006482 DOI: 10.1016/j.bbrc.2014.04.017

evidence_span

{"source_cache": "artifacts/dim-research/24127581.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6e938b73271132ed6dc4ed9f3a4d7bb6cf85fd3071df159c17c9fcef93b901fc", "start_char": 0, "end_char": 1379, "text_sha256": "6e938b73271132ed6dc4ed9f3a4d7bb6cf85fd3071df159c17c9fcef93b901fc"}

experimental_model

Cell signaling and rodent radiation experiments

exposure

Submicromolar cell exposures and multidose rodent DIM schedules

limitations

No human radioprotection trial. Lack of protection in tested tumor xenografts cannot establish safety with all radiotherapy or cancer types.

nutrient_topic

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

organism

Cultured cells and irradiated rodents; breast-tumor xenografts separately

plain_language

The compound also affected a DNA-damage sensor.

primary_references

[dim-p24127581] DIM (3,3'-diindolylmethane) confers protection against ionizing radiation by a unique mechanism. (2013). https://pubmed.ncbi.nlm.nih.gov/24127581/ DOI: 10.1073/pnas.1308206110

tissue_or_cell_type

ATM-mediated damage response

Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1429–1440

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

### dim-atm-response DIM rapidly activated ATM and enhanced ATM-linked DNA-damage-response signaling in the studied cell system. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The compound also affected a DNA-damage sensor. organism: Cultured cells and irradiated rodents; breast-tumor xenografts separately tissue_or_cell_type: ATM-mediated damage response experimental_model: Cell signaling and rodent radiation experiments limitations: No human radioprotection trial. Lack of protection in tested tumor xenografts cannot establish safety with all radiotherapy or cancer types. exposure: Submicromolar cell exposures and multidose rodent DIM schedules evidence_span: {"source_cache": "artifacts/dim-research/24127581.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6e938b73271132ed6dc4ed9f3a4d7bb6cf85fd3071df159c17c9fcef93b901fc", "start_char": 0, "end_char": 1379, "text_sha256": "6e938b73271132ed6dc4ed9f3a4d7bb6cf85fd3071df159c17c9fcef93b901fc"} [dim-p24127581] DIM (3,3'-diindolylmethane) confers protection against ionizing radiation by a unique mechanism. (2013). https://pubmed.ncbi.nlm.nih.gov/24127581/ DOI: 10.1073/pnas.1308206110

dose

Eugenol with CAY10502 or BAY11-7082 pathway probes

duration

Acute

evidence_access

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

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Platelets from healthy human donors; mouse mesenteric-thrombosis arm

limitations

Anucleate platelet NF-kappaB signaling and mouse plug formation do not establish chronic human outcomes.

nutrient_topic

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

organism

Platelets from healthy human donors; mouse mesenteric-thrombosis arm

plain_language

Eugenol reduced collagen-stimulated IKK and p65 phosphorylation and I-kappaB-alpha degradation; inhibitor ordering placed cPLA2 upstream of NF-kappaB in human platelets.

primary_references

Eugenol: A Potential Modulator of Human Platelet Activation and Mouse Mesenteric Vascular Thrombosis via an Innovative cPLA2-NF-κB Signaling Axis. (2024). https://pubmed.ncbi.nlm.nih.gov/39200154/ DOI: 10.3390/biomedicines12081689

route

In vitro and in vivo mouse model

tissue

cPLA2 and NF-kappaB signaling

Eugenol: mechanism of action and interactions (2026-09-20) · lines 33–42

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Platelets from healthy human donors; mouse mesenteric-thrombosis arm · source_derived_draft · unverified_draft

## eugenol-cpla2-nfkb Eugenol reduced collagen-stimulated IKK and p65 phosphorylation and I-kappaB-alpha degradation; inhibitor ordering placed cPLA2 upstream of NF-kappaB in human platelets. Model/species: Platelets from healthy human donors; mouse mesenteric-thrombosis arm Tissue/system: cPLA2 and NF-kappaB signaling Exposure: Eugenol with CAY10502 or BAY11-7082 pathway probes Route: In vitro and in vivo mouse model Duration: Acute Limits: Anucleate platelet NF-kappaB signaling and mouse plug formation do not establish chronic human outcomes. Primary reference: Eugenol: A Potential Modulator of Human Platelet Activation and Mouse Mesenteric Vascular Thrombosis via an Innovative cPLA2-NF-κB Signaling Axis. (2024). https://pubmed.ncbi.nlm.nih.gov/39200154/ DOI: 10.3390/biomedicines12081689 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_access

Primary abstract

experimental_model

Mouse chondrocytes; 10 ng/mL IL-1beta; DMM mouse OA model.

limitations

Not human osteoarthritis treatment evidence; direct Sirt6 binding is not established by this abstract.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

Cartilage cells provide another signaling context.

primary_references

Ergothioneine inhibits the progression of osteoarthritis via the Sirt6/NF-κB axis both in vitro and in vivo. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37156032/ · DOI 10.1016/j.intimp.2023.110211

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 368–374

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse chondrocytes; 10 ng/mL IL-1beta; DMM mouse OA model. · source_derived_draft · unverified_draft

## ergothioneine-mouse-cartilage Cartilage cells provide another signaling context. Ergothioneine treatment reduced inflammatory and matrix-degrading responses in IL-1beta-stimulated mouse chondrocytes through a reported Sirt6/NF-kappaB axis. Model: Mouse chondrocytes; 10 ng/mL IL-1beta; DMM mouse OA model. Limitations: Not human osteoarthritis treatment evidence; direct Sirt6 binding is not established by this abstract. Evidence access: Primary abstract Ergothioneine inhibits the progression of osteoarthritis via the Sirt6/NF-κB axis both in vitro and in vivo. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37156032/ · DOI 10.1016/j.intimp.2023.110211

evidence_access

Primary full text and abstract

experimental_model

THP1 and peripheral-blood-derived macrophages; purified protein exposure.

limitations

This differs from intracellular charging and from assays of individual fragments.

nutrient_topic

L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine

plain_language

A protein used for translation also signals outside cells.

primary_references

Moonlighting matrix metalloproteinase substrates: Enhancement of proinflammatory functions of extracellular tyrosyl-tRNA synthetase upon cleavage. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31771979/ · DOI 10.1074/jbc.RA119.010486

L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 108–114

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · THP1 and peripheral-blood-derived macrophages; purified protein exposure. · source_derived_draft · unverified_draft

## l-tyrosine-yrs-tlr2 A protein used for translation also signals outside cells. Extracellular YARS1 activated TLR2 signaling and inflammatory mediator release in human monocyte/macrophage preparations. Model: THP1 and peripheral-blood-derived macrophages; purified protein exposure. Limitations: This differs from intracellular charging and from assays of individual fragments. Evidence access: Primary full text and abstract Moonlighting matrix metalloproteinase substrates: Enhancement of proinflammatory functions of extracellular tyrosyl-tRNA synthetase upon cleavage. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31771979/ · DOI 10.1074/jbc.RA119.010486

evidence_access

Primary abstract

experimental_model

20 mM glucose for 48 hours with osmotic and normoglycemic controls.

limitations

Combination activity is not demonstrated clinical synergy; assess interaction statistics before claiming more-than-additive benefit.

nutrient_topic

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

plain_language

Two compounds were actually tested together.

primary_references

Combination Treatments with Luteolin and Fisetin Enhance Anti-Inflammatory Effects in High Glucose-Treated THP-1 Cells Through Histone Acetyltransferase/Histone Deacetylase Regulation. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28650731/ · DOI 10.1089/jmf.2017.3968

Fisetin: metabolism, cell-state responses and cross-nutrient mechanisms (2026-09-19) · lines 440–446

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 20 mM glucose for 48 hours with osmotic and normoglycemic controls. · source_derived_draft · unverified_draft

## fisetin-luteolin-combination Two compounds were actually tested together. In high-glucose-treated human THP-1 cells, 500 nM fisetin plus 500 nM or 1 micromolar luteolin suppressed inflammatory output. Model: 20 mM glucose for 48 hours with osmotic and normoglycemic controls. Limitations: Combination activity is not demonstrated clinical synergy; assess interaction statistics before claiming more-than-additive benefit. Evidence access: Primary abstract Combination Treatments with Luteolin and Fisetin Enhance Anti-Inflammatory Effects in High Glucose-Treated THP-1 Cells Through Histone Acetyltransferase/Histone Deacetylase Regulation. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28650731/ · DOI 10.1089/jmf.2017.3968

evidence_access

Primary abstract

experimental_model

Human gastric adenocarcinoma cell line, H. pylori challenge.

limitations

Not a clinical eradication trial and not proof of identical behavior in normal gastric tissue.

nutrient_topic

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

plain_language

The challenged gastric cells produced a smaller inflammatory signal.

primary_references

Astaxanthin Inhibits Mitochondrial Dysfunction and Interleukin-8 Expression in Helicobacter pylori-Infected Gastric Epithelial Cells. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30231525/ · DOI 10.3390/nu10091320

Astaxanthin: transport, membrane chemistry, signaling and nutrient interactions (2026-09-19) · lines 294–300

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human gastric adenocarcinoma cell line, H. pylori challenge. · source_derived_draft · unverified_draft

## astaxanthin-gastric-il8 The challenged gastric cells produced a smaller inflammatory signal. Astaxanthin reduced H. pylori-induced ROS, NF-kappa-B activation and IL-8 expression in human AGS cells. Model: Human gastric adenocarcinoma cell line, H. pylori challenge. Limitations: Not a clinical eradication trial and not proof of identical behavior in normal gastric tissue. Evidence access: Primary abstract Astaxanthin Inhibits Mitochondrial Dysfunction and Interleukin-8 Expression in Helicobacter pylori-Infected Gastric Epithelial Cells. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30231525/ · DOI 10.3390/nu10091320

dose

Naringenin 100 mg/kg/day by gavage in the mouse arm

duration

7 days in mice

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

Wild-type and NLRP3-knockout mice; HepG2 cells, hepatocytes and Kupffer cells

limitations

The methionine/choline-deficient model and high dose do not reproduce ordinary citrus intake or all human NAFLD.

nutrient_topic

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

organism

Wild-type and NLRP3-knockout mice; HepG2 cells, hepatocytes and Kupffer cells

plain_language

Naringenin reduced lipid accumulation and inflammatory signaling in methionine/choline-deficient mice and cells; effects were lost in NLRP3-null hepatocytes and restored after NLRP3 re-expression.

primary_references

Naringenin attenuates non-alcoholic fatty liver disease by down-regulating the NLRP3/NF-κB pathway in mice. (2020). https://pubmed.ncbi.nlm.nih.gov/31758699/ DOI: 10.1111/bph.14938

route

Oral and in vitro

tissue

NAFLD lipid accumulation and NLRP3/NF-kappaB signaling

Naringenin: mechanism of action and interactions (2026-09-20) · lines 121–130

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Wild-type and NLRP3-knockout mice; HepG2 cells, hepatocytes and Kupffer cells · source_derived_draft · unverified_draft

## naringenin-nlrp3-dependence Naringenin reduced lipid accumulation and inflammatory signaling in methionine/choline-deficient mice and cells; effects were lost in NLRP3-null hepatocytes and restored after NLRP3 re-expression. Model/species: Wild-type and NLRP3-knockout mice; HepG2 cells, hepatocytes and Kupffer cells Tissue/system: NAFLD lipid accumulation and NLRP3/NF-kappaB signaling Exposure: Naringenin 100 mg/kg/day by gavage in the mouse arm Route: Oral and in vitro Duration: 7 days in mice Limits: The methionine/choline-deficient model and high dose do not reproduce ordinary citrus intake or all human NAFLD. Primary reference: Naringenin attenuates non-alcoholic fatty liver disease by down-regulating the NLRP3/NF-κB pathway in mice. (2020). https://pubmed.ncbi.nlm.nih.gov/31758699/ DOI: 10.1111/bph.14938 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.