Human PPAR alpha / PPARA

evidence_span

{"source_cache": "artifacts/ibuprofen-research/11755111.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1dd77f4a1eebd7777285c424b1731f4744d0fa593e62cfbde0a92dbb6242b239", "start_char": 0, "end_char": 2074, "text_sha256": "1dd77f4a1eebd7777285c424b1731f4744d0fa593e62cfbde0a92dbb6242b239"}

experimental_model

Reporter and enzyme assays comparing ibuprofen isomers against naproxen and indomethacin across four readouts

exposure

S(+)- and R(-)-ibuprofen compared directly on cyclooxygenase-1 and -2, platelet function and nuclear receptor activation

limitations

The only record here that measures both enantiomers on the same panel, which is what makes the fold-differences meaningful. Several different assay systems are combined.

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

Rat, human and sheep systems

plain_language

Both hands switch on the fat-handling nuclear receptors, with a much smaller gap between them than at cyclooxygenase.

primary_references

[ibu-p11755111] Activation of peroxisome proliferator-activated receptor isoforms and inhibition of prostaglandin H(2) synthases by ibuprofen, naproxen, and indomethacin. (2001). https://pubmed.ncbi.nlm.nih.gov/11755111/ DOI: 10.1016/s0006-2952(01)00822-x

tissue_or_cell_type

Transfected cells, hepatoma cells, platelets and purified enzyme

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 331–342

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reporter and enzyme assays comparing ibuprofen isomers against naproxen and indomethacin across four readouts · source_derived_draft · unverified_draft

### ibu-both-isomers-hit-ppar Each drug tested produced concentration-dependent activation of peroxisome proliferator-activated receptor alpha and gamma isoforms and of peroxisomal fatty acyl-CoA beta-oxidase activity, with a rank order of stereoselectivity for alpha activation and fatty acyl oxidase stimulation of S(+)-ibuprofen greater than R(-)-ibuprofen, S(+)-ibuprofen being more potent than indomethacin and naproxen on these parameters, while on gamma the order was S(+)-naproxen greater than indomethacin greater than S(+)-ibuprofen greater than R(-)-ibuprofen. 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: Both hands switch on the fat-handling nuclear receptors, with a much smaller gap between them than at cyclooxygenase. organism: Rat, human and sheep systems tissue_or_cell_type: Transfected cells, hepatoma cells, platelets and purified enzyme experimental_model: Reporter and enzyme assays comparing ibuprofen isomers against naproxen and indomethacin across four readouts limitations: The only record here that measures both enantiomers on the same panel, which is what makes the fold-differences meaningful. Several different assay systems are combined. exposure: S(+)- and R(-)-ibuprofen compared directly on cyclooxygenase-1 and -2, platelet function and nuclear receptor activation evidence_span: {"source_cache": "artifacts/ibuprofen-research/11755111.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1dd77f4a1eebd7777285c424b1731f4744d0fa593e62cfbde0a92dbb6242b239", "start_char": 0, "end_char": 2074, "text_sha256": "1dd77f4a1eebd7777285c424b1731f4744d0fa593e62cfbde0a92dbb6242b239"} [ibu-p11755111] Activation of peroxisome proliferator-activated receptor isoforms and inhibition of prostaglandin H(2) synthases by ibuprofen, naproxen, and indomethacin. (2001). https://pubmed.ncbi.nlm.nih.gov/11755111/ DOI: 10.1016/s0006-2952(01)00822-x

evidence_access

Primary full text, methods 2.4 and SPR results

experimental_model

Recombinant human receptor-domain biochemistry.

limitations

Domain binding does not establish receptor occupancy after oral supplementation.

nutrient_topic

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

plain_language

A purified receptor domain interacted directly with the molecule.

primary_references

The natural carotenoid astaxanthin, a PPAR-α agonist and PPAR-γ antagonist, reduces hepatic lipid accumulation by rewiring the transcriptome in lipid-loaded hepatocytes. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22707263/ · DOI 10.1002/mnfr.201100798

Astaxanthin: transport, membrane chemistry, signaling and nutrient interactions (2026-09-19) · lines 246–252

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human receptor-domain biochemistry. · source_derived_draft · unverified_draft

## astaxanthin-ppara-binding A purified receptor domain interacted directly with the molecule. Surface-plasmon-resonance assays detected binding of astaxanthin to recombinant human PPAR-alpha ligand-binding domains. Model: Recombinant human receptor-domain biochemistry. Limitations: Domain binding does not establish receptor occupancy after oral supplementation. Evidence access: Primary full text, methods 2.4 and SPR results The natural carotenoid astaxanthin, a PPAR-α agonist and PPAR-γ antagonist, reduces hepatic lipid accumulation by rewiring the transcriptome in lipid-loaded hepatocytes. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22707263/ · DOI 10.1002/mnfr.201100798

evidence_span

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experimental_model

Human HepG2 cells and mice given acute and repeated doses, with PPAR-alpha-deficient animals and a human case

exposure

0.5 to 20 millimolar in cells and 750 milligrams per kilogram in mice, acute and repeated over four days

limitations

Follows a lipid signalling system across cells, mice, knockouts and one human case. The biphasic time course is the informative part and complicates any single-timepoint reading.

nutrient_topic

Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404. · Paracetamol

organism

Human cells, mouse and human

plain_language

The same lipid system that makes the painkilling metabolite is knocked down by an overdose and then rebounds, and animals lacking it fare worse.

primary_references

[apap-p29056914] Acetaminophen-Induced Liver Injury Alters the Acyl Ethanolamine-Based Anti-Inflammatory Signaling System in Liver. (2017). https://pubmed.ncbi.nlm.nih.gov/29056914/ DOI: 10.3389/fphar.2017.00705

tissue_or_cell_type

Liver

Paracetamol: the enzyme it reduces rather than blocks, the isoform that turned out not to exist, the metabolite that carries the analgesia, and the metabolite that destroys the liver (2026-09-22) · lines 441–452

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human HepG2 cells and mice given acute and repeated doses, with PPAR-alpha-deficient animals and a human case · source_derived_draft · unverified_draft

### apap-the-lipid-brake-fails-then-rebounds Acetaminophen produced a biphasic response in the N-acyl ethanolamide and PPAR alpha system, with decreased PPAR alpha expression after 6 hours followed by a generalised increase of system components including PPAR alpha, NAPE-PLD and fatty acid amide hydrolase and of the N-acyl ethanolamides after 24 hours, confirmed in mice where gene expression of PPAR alpha and fatty acid amide hydrolase fell at 6 hours and rose by 24 hours, repeated administration decreased both and increased liver N-acyl ethanolamides with complete restoration after 15 days of rest, immunohistochemistry in a human case of acetaminophen hepatotoxicity confirmed the decrements, and damage-related alterations after repeated administration were aggravated in PPAR alpha-deficient mice. Condition category: normal nutrient_topic: Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404. plain_language: The same lipid system that makes the painkilling metabolite is knocked down by an overdose and then rebounds, and animals lacking it fare worse. organism: Human cells, mouse and human tissue_or_cell_type: Liver experimental_model: Human HepG2 cells and mice given acute and repeated doses, with PPAR-alpha-deficient animals and a human case limitations: Follows a lipid signalling system across cells, mice, knockouts and one human case. The biphasic time course is the informative part and complicates any single-timepoint reading. exposure: 0.5 to 20 millimolar in cells and 750 milligrams per kilogram in mice, acute and repeated over four days evidence_span: {"source_cache": "artifacts/paracetamol-research/29056914.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2ca7517052bab3c774f315af85f3aa8cdf810e43dc44444724bff46e2f1bdab3", "start_char": 0, "end_char": 2081, "text_sha256": "2ca7517052bab3c774f315af85f3aa8cdf810e43dc44444724bff46e2f1bdab3"} [apap-p29056914] Acetaminophen-Induced Liver Injury Alters the Acyl Ethanolamine-Based Anti-Inflammatory Signaling System in Liver. (2017). https://pubmed.ncbi.nlm.nih.gov/29056914/ DOI: 10.3389/fphar.2017.00705