Human NF-kappa-B p65 / RELA

evidence_access

Primary abstract

experimental_model

Human adipocyte RNA-interference experiment.

limitations

Supports a contribution in this model, not universal necessity in all tissues.

nutrient_topic

CLA collection; isomer, preparation, species, exposure and manipulation remain explicit. · Conjugated linoleic acid / CLA isomer family

plain_language

Removing a signaling component weakened the adverse response.

primary_references

Conjugated linoleic acid promotes human adipocyte insulin resistance through NFkappaB-dependent cytokine production. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16155293/ · DOI 10.1074/jbc.M508159200

Conjugated linoleic acid: isomers, signaling, nutrient interactions and discovery (2026-09-19) · lines 142–148

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human adipocyte RNA-interference experiment. · source_derived_draft · unverified_draft

## cla-rela-knockdown Removing a signaling component weakened the adverse response. p65 siRNA depletion attenuated CLA-induced loss of GLUT4 and PPAR-gamma proteins and suppression of glucose uptake. Model: Human adipocyte RNA-interference experiment. Limitations: Supports a contribution in this model, not universal necessity in all tissues. Evidence access: Primary abstract Conjugated linoleic acid promotes human adipocyte insulin resistance through NFkappaB-dependent cytokine production. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16155293/ · DOI 10.1074/jbc.M508159200

evidence_access

Primary full text

experimental_model

Human primary monocytes and U937 cells; Esther 20% stock diluted to 0.5-10 micrograms/mL, 4-hour pretreatment; homocysteine stimulation.

limitations

Cell exposure does not establish oral exposure, homocysteine removal or cardiovascular benefit. Results text reports homocysteine 200 micromolar, while figure captions say 200 micrograms/mL; dose units are unresolved. Inhibitor concentrations also need original-record clarification. ChIP is a cultured-cell result; the paper uses in vivo to mean within cells.

nutrient_topic

Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)

plain_language

The inflammatory transcription factor occupied the promoter less.

primary_references

Fulvic acid attenuates homocysteine-induced cyclooxygenase-2 expression in human monocytes. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25888188/ · DOI 10.1186/s12906-015-0583-x

Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 52–58

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human primary monocytes and U937 cells; Esther 20% stock diluted to 0.5-10 micrograms/mL, 4-hour pretreatment; homocysteine stimulation. · source_derived_draft · unverified_draft

## fulvic-acid-p65-binding The inflammatory transcription factor occupied the promoter less. Fulvic pretreatment reduced p65 binding at the COX-2 promoter in stimulated U937 cells. Model: Human primary monocytes and U937 cells; Esther 20% stock diluted to 0.5-10 micrograms/mL, 4-hour pretreatment; homocysteine stimulation. Limitations: Cell exposure does not establish oral exposure, homocysteine removal or cardiovascular benefit. Results text reports homocysteine 200 micromolar, while figure captions say 200 micrograms/mL; dose units are unresolved. Inhibitor concentrations also need original-record clarification. ChIP is a cultured-cell result; the paper uses in vivo to mean within cells. Evidence access: Primary full text Fulvic acid attenuates homocysteine-induced cyclooxygenase-2 expression in human monocytes. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25888188/ · DOI 10.1186/s12906-015-0583-x

evidence_access

Primary abstract

experimental_model

Human adipocyte/stromal-vascular cultures and explants.

limitations

Different cell populations contribute to the response.

nutrient_topic

CLA collection; isomer, preparation, species, exposure and manipulation remain explicit. · Conjugated linoleic acid / CLA isomer family

plain_language

Inflammatory signaling became active in the fat-cell cultures.

primary_references

Conjugated linoleic acid promotes human adipocyte insulin resistance through NFkappaB-dependent cytokine production. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16155293/ · DOI 10.1074/jbc.M508159200

Conjugated linoleic acid: isomers, signaling, nutrient interactions and discovery (2026-09-19) · lines 126–132

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human adipocyte/stromal-vascular cultures and explants. · source_derived_draft · unverified_draft

## cla-nfkb Inflammatory signaling became active in the fat-cell cultures. Adding t10,c12 CLA promoted NF-kappa-B activation, including p65 phosphorylation and nuclear translocation with I-kappa-B-alpha degradation. Model: Human adipocyte/stromal-vascular cultures and explants. Limitations: Different cell populations contribute to the response. Evidence access: Primary abstract Conjugated linoleic acid promotes human adipocyte insulin resistance through NFkappaB-dependent cytokine production. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16155293/ · DOI 10.1074/jbc.M508159200

evidence_span

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experimental_model

Electrophoretic mobility-shift assays, transient transfection, confocal immunofluorescence and nuclear import experiments

exposure

R(-)- and S(+)-ibuprofen compared as inhibitors of nuclear factor kappa B activation

limitations

Compares the enantiomers on a target where the cyclooxygenase argument does not apply. The concentrations are high, in the tens to hundreds of micromolar.

nutrient_topic

Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen

organism

Human cells

plain_language

On this target the two hands are only twofold apart, not thirty, which is a route by which the so-called inactive one could work.

primary_references

[ibu-p9517383] Modulation of transcription factor NF-kappaB by enantiomers of the nonsteroidal drug ibuprofen. (1998). https://pubmed.ncbi.nlm.nih.gov/9517383/ DOI: 10.1038/sj.bjp.0701652

tissue_or_cell_type

T lymphocytes

Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 370–381

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Electrophoretic mobility-shift assays, transient transfection, confocal immunofluorescence and nuclear import experiments · source_derived_draft · unverified_draft

### ibu-both-hands-block-nfkb R(-)-ibuprofen with a half-maximal inhibitory concentration of 121.8 micromolar and S(+)-ibuprofen at 61.7 micromolar both inhibited activation of nuclear factor kappa B in response to T-cell stimulation, the effect was specific in that ibuprofen up to 10 millimolar did not affect heat shock transcription factor or activation by prostaglandin E2, concentrations of 20 millimolar did not prevent binding to DNA in vitro, and immunofluorescence and nuclear import experiments indicate the site of action is upstream of dissociation of the nuclear factor kappa B-I-kappa-B complex; only the S(+) enantiomer is an effective cyclooxygenase inhibitor, so the mechanism by which R(-) exerts anti-inflammatory and antinociceptive effects remains unknown. Condition category: normal nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: On this target the two hands are only twofold apart, not thirty, which is a route by which the so-called inactive one could work. organism: Human cells tissue_or_cell_type: T lymphocytes experimental_model: Electrophoretic mobility-shift assays, transient transfection, confocal immunofluorescence and nuclear import experiments limitations: Compares the enantiomers on a target where the cyclooxygenase argument does not apply. The concentrations are high, in the tens to hundreds of micromolar. exposure: R(-)- and S(+)-ibuprofen compared as inhibitors of nuclear factor kappa B activation evidence_span: {"source_cache": "artifacts/ibuprofen-research/9517383.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7a3938a95448a472769fdce1c05ac55d853bfdbdbcda7554ec5b79dcb423db35", "start_char": 0, "end_char": 1478, "text_sha256": "7a3938a95448a472769fdce1c05ac55d853bfdbdbcda7554ec5b79dcb423db35"} [ibu-p9517383] Modulation of transcription factor NF-kappaB by enantiomers of the nonsteroidal drug ibuprofen. (1998). https://pubmed.ncbi.nlm.nih.gov/9517383/ DOI: 10.1038/sj.bjp.0701652

evidence_span

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experimental_model

Primary human endothelial cells stimulated with tumour necrosis factor alpha, with viability, adhesion and radical scavenging assays

exposure

Dihydrocapsaicin from below 50 up to 500 micromolar, against capsaicin and vitamin C

limitations

The only head-to-head cytotoxicity comparison in this collection. Concentrations of 100 micromolar and above are far higher than any plasma level reported here.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Human

plain_language

Below the toxic range it calms the inflamed vessel lining and stops immune cells sticking to it.

primary_references

[dhc-p36007275] Beneficial effects of capsaicin and dihydrocapsaicin on endothelial inflammation, nitric oxide production and antioxidant activity. (2022). https://pubmed.ncbi.nlm.nih.gov/36007275/ DOI: 10.1016/j.biopha.2022.113521

tissue_or_cell_type

Vascular endothelium

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 673–684

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary human endothelial cells stimulated with tumour necrosis factor alpha, with viability, adhesion and radical scavenging assays · source_derived_draft · unverified_draft

### dhc-endothelial-anti-inflammatory Tumour necrosis factor alpha induced Ser536 phosphorylation of p65 NF-kappa-B, expression of vascular cell adhesion molecule 1 and intercellular adhesion molecule 1, and interleukin 6 production in primary human endothelial cells, and these effects were robustly abrogated by dihydrocapsaicin, which also led to a marked reduction in tumour-necrosis-factor-mediated monocyte adhesion to endothelial cells. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: Below the toxic range it calms the inflamed vessel lining and stops immune cells sticking to it. organism: Human tissue_or_cell_type: Vascular endothelium experimental_model: Primary human endothelial cells stimulated with tumour necrosis factor alpha, with viability, adhesion and radical scavenging assays limitations: The only head-to-head cytotoxicity comparison in this collection. Concentrations of 100 micromolar and above are far higher than any plasma level reported here. exposure: Dihydrocapsaicin from below 50 up to 500 micromolar, against capsaicin and vitamin C evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/36007275.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b04a74a345c83df1454aa34ad591c7cefd04325de39cde8d5118bbea005aba3b", "start_char": 0, "end_char": 1605, "text_sha256": "b04a74a345c83df1454aa34ad591c7cefd04325de39cde8d5118bbea005aba3b"} [dhc-p36007275] Beneficial effects of capsaicin and dihydrocapsaicin on endothelial inflammation, nitric oxide production and antioxidant activity. (2022). https://pubmed.ncbi.nlm.nih.gov/36007275/ DOI: 10.1016/j.biopha.2022.113521

evidence_span

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experimental_model

Electrophoretic mobility shift and reporter transcription assays in transfected T cells

exposure

Sodium salicylate and aspirin applied to nuclear factor kappa B activation

limitations

A cell-based mechanism recorded at the concentrations used in the assay, which are far above those reached by antiplatelet dosing. It does not distinguish the two compounds from one another.

nutrient_topic

Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. · Aspirin / acetylsalicylic acid

organism

Human cells

plain_language

Both compounds keep an inflammatory master switch locked out of the nucleus.

primary_references

[asa-p8052854] Inhibition of NF-kappa B by sodium salicylate and aspirin. (1994). https://pubmed.ncbi.nlm.nih.gov/8052854/ DOI: 10.1126/science.8052854

tissue_or_cell_type

T lymphocytes

Aspirin: the serine it acetylates, the enzyme that acetylation creates, the dose that separates platelet from vessel wall, and the metabolite that is a different drug (2026-09-22) · lines 468–479

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Electrophoretic mobility shift and reporter transcription assays in transfected T cells · source_derived_draft · unverified_draft

### asa-salicylate-blocks-nfkb The anti-inflammatory drugs sodium salicylate and aspirin inhibited activation of nuclear factor kappa B, an inhibition which prevented degradation of the inhibitor I-kappa-B so that nuclear factor kappa B was retained in the cytosol, and both also inhibited nuclear factor kappa B-dependent transcription from the immunoglobulin kappa enhancer and the human immunodeficiency virus long terminal repeat in transfected T cells. Condition category: normal nutrient_topic: Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. plain_language: Both compounds keep an inflammatory master switch locked out of the nucleus. organism: Human cells tissue_or_cell_type: T lymphocytes experimental_model: Electrophoretic mobility shift and reporter transcription assays in transfected T cells limitations: A cell-based mechanism recorded at the concentrations used in the assay, which are far above those reached by antiplatelet dosing. It does not distinguish the two compounds from one another. exposure: Sodium salicylate and aspirin applied to nuclear factor kappa B activation evidence_span: {"source_cache": "artifacts/aspirin-research/8052854.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d1d488e1bc53706da4f733f3fecc2bb981c09c0aa2dccae2bac9fac1bb04cec1", "start_char": 0, "end_char": 737, "text_sha256": "d1d488e1bc53706da4f733f3fecc2bb981c09c0aa2dccae2bac9fac1bb04cec1"} [asa-p8052854] Inhibition of NF-kappa B by sodium salicylate and aspirin. (1994). https://pubmed.ncbi.nlm.nih.gov/8052854/ DOI: 10.1126/science.8052854