Human I-kappa-B alpha / NFKBIA

Where it participates (unsigned role)

1. Cucurbitacin B reduced TNF-alpha-induced RelA nuclear translocation and I-kappa-B-alpha phosphorylation in human A549 cells.

   Cucurbitacin B → Human NF-kappa-B subunit RelA / RELA source_derived_draftungraded
   Experimental context and source evidence

   evidence_access

   Primary abstract

   experimental_model

   Human A549 cytokine-stimulation assays.

   limitations

   Downstream readouts do not establish direct inhibition of each protein.

   nutrient_topic

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

   plain_language

   Less inflammatory transcription signaling reached the nucleus.

   primary_references

   Cucurbitacin B Down-Regulates TNF Receptor 1 Expression and Inhibits the TNF-α-Dependent Nuclear Factor κB Signaling Pathway in Human Lung Adenocarcinoma A549 Cells. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35806134/ · DOI 10.3390/ijms23137130

   Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 204–210

   AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human A549 cytokine-stimulation assays. · source_derived_draft · unverified_draft

   ## cucurbitacin-b-rela Less inflammatory transcription signaling reached the nucleus. Cucurbitacin B reduced TNF-alpha-induced RelA nuclear translocation and I-kappa-B-alpha phosphorylation in human A549 cells. Model: Human A549 cytokine-stimulation assays. Limitations: Downstream readouts do not establish direct inhibition of each protein. Evidence access: Primary abstract Cucurbitacin B Down-Regulates TNF Receptor 1 Expression and Inhibits the TNF-α-Dependent Nuclear Factor κB Signaling Pathway in Human Lung Adenocarcinoma A549 Cells. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35806134/ · DOI 10.3390/ijms23137130

   Complete structured claim and evidence

2. 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.

   R(-)-ibuprofen → Activation of nuclear factor kappa B in response to T-cell stimulation source_derived_draftungraded
   Experimental context and source evidence

   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"}

   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

   Complete structured claim and evidence

3. All-E, 9Z and 13Z astaxanthin at 1.2 micromolar reduced TNF-induced IL-8 secretion by 22–27% in Caco-2 cells, with reduced I-kappa-B-alpha phosphorylation.

   Astaxanthin → Human interleukin-8 / CXCL8 source_derived_draftungraded
   Experimental context and source evidence

   evidence_access

   Primary abstract

   experimental_model

   Human Caco-2 monolayers with TNF challenge.

   limitations

   Different isomer responses do not establish a preferred clinical formulation.

   nutrient_topic

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

   plain_language

   The absorbed forms also changed inflammatory signaling in intestinal cells.

   primary_references

   Anti-Inflammatory Effects of Different Astaxanthin Isomers and the Roles of Lipid Transporters in the Cellular Transport of Astaxanthin Isomers in Caco-2 Cell Monolayers. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31117505/ · DOI 10.1021/acs.jafc.9b02102

   Astaxanthin: transport, membrane chemistry, signaling and nutrient interactions (2026-09-19) · lines 486–492

   AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human Caco-2 monolayers with TNF challenge. · source_derived_draft · unverified_draft

   ## astaxanthin-intestinal-inflammatory-signal The absorbed forms also changed inflammatory signaling in intestinal cells. All-E, 9Z and 13Z astaxanthin at 1.2 micromolar reduced TNF-induced IL-8 secretion by 22–27% in Caco-2 cells, with reduced I-kappa-B-alpha phosphorylation. Model: Human Caco-2 monolayers with TNF challenge. Limitations: Different isomer responses do not establish a preferred clinical formulation. Evidence access: Primary abstract Anti-Inflammatory Effects of Different Astaxanthin Isomers and the Roles of Lipid Transporters in the Cellular Transport of Astaxanthin Isomers in Caco-2 Cell Monolayers. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31117505/ · DOI 10.1021/acs.jafc.9b02102

   Complete structured claim and evidence

4. Adding t10,c12 CLA promoted NF-kappa-B activation, including p65 phosphorylation and nuclear translocation with I-kappa-B-alpha degradation.

   trans-10,cis-12 conjugated linoleic acid → Human NF-kappa-B p65 / RELA source_derived_draftungraded
   Experimental context and source evidence

   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

   Complete structured claim and evidence

5. Sodium salicylate inhibited activation of nuclear factor kappa B by preventing phosphorylation and subsequent degradation of I-kappa-B-alpha without affecting tumour necrosis factor alpha-induced phosphorylation of ATF-2, blocked the increase in adhesion molecule messenger RNA and gave dose-dependent inhibition of surface vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 with higher doses required for endothelial-leukocyte adhesion molecule 1, and inhibited transendothelial migration of neutrophils; indomethacin, a nonsalicylate cyclooxygenase inhibitor, had no effect on surface expression, suggesting the effects were not due to inhibition of cyclooxygenase.

   Salicylate / salicylic acid → Surface expression of endothelial leukocyte adhesion molecules source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/aspirin-research/8621937.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9b5aff676845bd0a47f25a0f63564880f70af7667b5ab9d667cece58d05356f1", "start_char": 0, "end_char": 1767, "text_sha256": "9b5aff676845bd0a47f25a0f63564880f70af7667b5ab9d667cece58d05356f1"}

   experimental_model

   Adhesion molecule expression, neutrophil adhesion and transendothelial migration in human umbilical vein endothelial cells

   exposure

   Sodium salicylate against tumour necrosis factor alpha stimulation, with indomethacin as a cyclooxygenase control

   limitations

   The indomethacin control is the important part: it shows the effect is not a cyclooxygenase effect. High salicylate concentrations, which the authors relate to high-dose therapy rather than to antiplatelet dosing.

   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

   A cyclooxygenase blocker does nothing here, so this arm of salicylate is not about prostaglandins at all.

   primary_references

   [asa-p8621937] Salicylates inhibit I kappa B-alpha phosphorylation, endothelial-leukocyte adhesion molecule expression, and neutrophil transmigration. (1996). https://pubmed.ncbi.nlm.nih.gov/8621937/ DOI: 10.4049/jimmunol.156.10.3961

   tissue_or_cell_type

   Endothelium

   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 481–492

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Adhesion molecule expression, neutrophil adhesion and transendothelial migration in human umbilical vein endothelial cells · source_derived_draft · unverified_draft

   ### asa-not-a-cyclooxygenase-effect Sodium salicylate inhibited activation of nuclear factor kappa B by preventing phosphorylation and subsequent degradation of I-kappa-B-alpha without affecting tumour necrosis factor alpha-induced phosphorylation of ATF-2, blocked the increase in adhesion molecule messenger RNA and gave dose-dependent inhibition of surface vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 with higher doses required for endothelial-leukocyte adhesion molecule 1, and inhibited transendothelial migration of neutrophils; indomethacin, a nonsalicylate cyclooxygenase inhibitor, had no effect on surface expression, suggesting the effects were not due to inhibition of cyclooxygenase. 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: A cyclooxygenase blocker does nothing here, so this arm of salicylate is not about prostaglandins at all. organism: Human cells tissue_or_cell_type: Endothelium experimental_model: Adhesion molecule expression, neutrophil adhesion and transendothelial migration in human umbilical vein endothelial cells limitations: The indomethacin control is the important part: it shows the effect is not a cyclooxygenase effect. High salicylate concentrations, which the authors relate to high-dose therapy rather than to antiplatelet dosing. exposure: Sodium salicylate against tumour necrosis factor alpha stimulation, with indomethacin as a cyclooxygenase control evidence_span: {"source_cache": "artifacts/aspirin-research/8621937.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9b5aff676845bd0a47f25a0f63564880f70af7667b5ab9d667cece58d05356f1", "start_char": 0, "end_char": 1767, "text_sha256": "9b5aff676845bd0a47f25a0f63564880f70af7667b5ab9d667cece58d05356f1"} [asa-p8621937] Salicylates inhibit I kappa B-alpha phosphorylation, endothelial-leukocyte adhesion molecule expression, and neutrophil transmigration. (1996). https://pubmed.ncbi.nlm.nih.gov/8621937/ DOI: 10.4049/jimmunol.156.10.3961

   Complete structured claim and evidence

6. 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.

   Salicylate / salicylic acid → Activation of nuclear factor kappa B source_derived_draftungraded
   Experimental context and source evidence

   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"}

   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

   Complete structured claim and evidence