Serotonin

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Rat gastric nutrient-sensing experiment.

limitations

Does not establish dietary tryptophan depletion from MSG or a human clinical syndrome.

nutrient_topic

Monosodium Glutamate (MSG) collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Monosodium L-glutamate

plain_language

A locally available mediator was required in the tested pathway.

primary_references

Luminal amino acid sensing in the rat gastric mucosa. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16809638/ · DOI 10.1152/ajpgi.00587.2005

trigger_kind

machinery_impairment Imported condition classification; unverified.

Monosodium Glutamate (MSG): taste, gut sensing, exposure and cross-nutrient mechanisms (2026-09-20) · lines 154–160

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat gastric nutrient-sensing experiment. · source_derived_draft · unverified_draft

## monosodium-glutamate-serotonin-gate A locally available mediator was required in the tested pathway. Serotonin depletion blocked glutamate-evoked gastric vagal firing in rats. Model: Rat gastric nutrient-sensing experiment. Limitations: Does not establish dietary tryptophan depletion from MSG or a human clinical syndrome. Evidence access: Primary abstract Luminal amino acid sensing in the rat gastric mucosa. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16809638/ · DOI 10.1152/ajpgi.00587.2005

experimental_model

Human DDC expressed in monkey COS cells; enzyme assays

exposure

PLP addition to transfected COS-cell enzyme incubations.

limitations

An expression-system response is not proof that supplements increase brain monoamines.

nutrient_topic

Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6

organism

Human DDC expressed in monkey COS cells

plain_language

B6 cofactor supports this monoamine-producing step.

primary_references

[sumi-1990-ddc] Characterization of recombinant human aromatic L-amino acid decarboxylase expressed in COS cells (1990). https://doi.org/10.1111/j.1471-4159.1990.tb04601.x DOI: 10.1111/j.1471-4159.1990.tb04601.x

tissue_or_cell_type

COS-cell expression system

Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1011–1021

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human DDC expressed in monkey COS cells; enzyme assays · source_derived_draft · unverified_draft

### b6-neuro-ddc-serotonin Expressed human DDC decarboxylated 5-hydroxy-L-tryptophan; added PLP enhanced the measured activity. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: B6 cofactor supports this monoamine-producing step. organism: Human DDC expressed in monkey COS cells tissue_or_cell_type: COS-cell expression system experimental_model: Human DDC expressed in monkey COS cells; enzyme assays limitations: An expression-system response is not proof that supplements increase brain monoamines. exposure: PLP addition to transfected COS-cell enzyme incubations. [sumi-1990-ddc] Characterization of recombinant human aromatic L-amino acid decarboxylase expressed in COS cells (1990). https://doi.org/10.1111/j.1471-4159.1990.tb04601.x DOI: 10.1111/j.1471-4159.1990.tb04601.x

evidence_span

{"source_cache": "artifacts/melatonin-research/29794137.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "051e28814382bea96e610c4cc406e7bc1d4d705d245b43dea0bba61050ae341e", "start_char": 0, "end_char": 1575, "text_sha256": "051e28814382bea96e610c4cc406e7bc1d4d705d245b43dea0bba61050ae341e"}

experimental_model

Isoform expression, transfection and metabolic measurements

exposure

HIOMT298 expression versus pineal HIOMT345

limitations

The 298-aa isoform was studied for 5-MTP production. Do not assign its anti-tumor findings to melatonin or assume all ASMT isoforms have identical products.

nutrient_topic

Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin

organism

Human fibroblasts, A549 cancer cells and mouse xenografts

plain_language

A shared enzyme name does not mean every isoform feeds the melatonin branch.

primary_references

[melatonin-p29794137] Restoration of hydroxyindole O-methyltransferase levels in human cancer cells induces a tryptophan-metabolic switch and attenuates cancer progression. (2018). https://pubmed.ncbi.nlm.nih.gov/29794137/ DOI: 10.1074/jbc.ra117.000597

tissue_or_cell_type

Alternative tryptophan metabolism

Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 344–355

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isoform expression, transfection and metabolic measurements · source_derived_draft · unverified_draft

### melatonin-asmt-isoform-serotonin-switch HIOMT298 expression shifted the measured tryptophan metabolism from serotonin toward 5-MTP production. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A shared enzyme name does not mean every isoform feeds the melatonin branch. organism: Human fibroblasts, A549 cancer cells and mouse xenografts tissue_or_cell_type: Alternative tryptophan metabolism experimental_model: Isoform expression, transfection and metabolic measurements limitations: The 298-aa isoform was studied for 5-MTP production. Do not assign its anti-tumor findings to melatonin or assume all ASMT isoforms have identical products. exposure: HIOMT298 expression versus pineal HIOMT345 evidence_span: {"source_cache": "artifacts/melatonin-research/29794137.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "051e28814382bea96e610c4cc406e7bc1d4d705d245b43dea0bba61050ae341e", "start_char": 0, "end_char": 1575, "text_sha256": "051e28814382bea96e610c4cc406e7bc1d4d705d245b43dea0bba61050ae341e"} [melatonin-p29794137] Restoration of hydroxyindole O-methyltransferase levels in human cancer cells induces a tryptophan-metabolic switch and attenuates cancer progression. (2018). https://pubmed.ncbi.nlm.nih.gov/29794137/ DOI: 10.1074/jbc.ra117.000597

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

At the first enzyme one hand is thirty to ninety times stronger; at the second enzyme the two hands are indistinguishable.

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 318–329

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-thirty-two-fold-at-cox1 The S(+) isomer of ibuprofen was 32-, 41- and 96-fold more potent than the R(-) isomer for inhibition of prostaglandin endoperoxide H synthase-1 activity, human platelet aggregation and serotonin secretion respectively, while on prostaglandin endoperoxide H synthase-2 the ibuprofen isomers showed no selectivity, and indomethacin, S(+)-ibuprofen and S(+)-naproxen were 6-, 27- and 5-fold more potent as inhibitors of synthase-1 than of synthase-2. 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: At the first enzyme one hand is thirty to ninety times stronger; at the second enzyme the two hands are indistinguishable. 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_span

{"source_cache": "artifacts/melatonin-research/10722724.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7fb8418b17e92c5b3fed5d9c08afdb32f28c922dfe94274d3bb02b7e12b2b8c8", "start_char": 0, "end_char": 1857, "text_sha256": "7fb8418b17e92c5b3fed5d9c08afdb32f28c922dfe94274d3bb02b7e12b2b8c8"}

experimental_model

Purified recombinant enzyme substrate-specificity study

exposure

Serotonin and radiolabeled acetyl-CoA; product HPLC

limitations

Biochemical mechanism, not evidence that dietary B5 or acetyl-CoA availability limits melatonin production in all humans.

nutrient_topic

Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin

organism

Human AANAT expressed in bacteria

plain_language

This connects melatonin synthesis to the B5-derived coenzyme-A system.

primary_references

[melatonin-p10722724] Substrate specificity and inhibition studies of human serotonin N-acetyltransferase. (2000). https://pubmed.ncbi.nlm.nih.gov/10722724/ DOI: 10.1074/jbc.275.12.8794

tissue_or_cell_type

Serotonin acetylation

Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 188–199

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant enzyme substrate-specificity study · source_derived_draft · unverified_draft

### melatonin-aanat-acetyl-coa The human AANAT assay used acetyl-CoA as the acetyl donor in N-acetylserotonin formation. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This connects melatonin synthesis to the B5-derived coenzyme-A system. organism: Human AANAT expressed in bacteria tissue_or_cell_type: Serotonin acetylation experimental_model: Purified recombinant enzyme substrate-specificity study limitations: Biochemical mechanism, not evidence that dietary B5 or acetyl-CoA availability limits melatonin production in all humans. exposure: Serotonin and radiolabeled acetyl-CoA; product HPLC evidence_span: {"source_cache": "artifacts/melatonin-research/10722724.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7fb8418b17e92c5b3fed5d9c08afdb32f28c922dfe94274d3bb02b7e12b2b8c8", "start_char": 0, "end_char": 1857, "text_sha256": "7fb8418b17e92c5b3fed5d9c08afdb32f28c922dfe94274d3bb02b7e12b2b8c8"} [melatonin-p10722724] Substrate specificity and inhibition studies of human serotonin N-acetyltransferase. (2000). https://pubmed.ncbi.nlm.nih.gov/10722724/ DOI: 10.1074/jbc.275.12.8794

evidence_span

{"source_cache": "artifacts/melatonin-research/10722724.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7fb8418b17e92c5b3fed5d9c08afdb32f28c922dfe94274d3bb02b7e12b2b8c8", "start_char": 0, "end_char": 1857, "text_sha256": "7fb8418b17e92c5b3fed5d9c08afdb32f28c922dfe94274d3bb02b7e12b2b8c8"}

experimental_model

Purified recombinant enzyme substrate-specificity study

exposure

Serotonin and radiolabeled acetyl-CoA; product HPLC

limitations

Biochemical mechanism, not evidence that dietary B5 or acetyl-CoA availability limits melatonin production in all humans.

nutrient_topic

Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin

organism

Human AANAT expressed in bacteria

plain_language

Serotonin is modified before it becomes melatonin.

primary_references

[melatonin-p10722724] Substrate specificity and inhibition studies of human serotonin N-acetyltransferase. (2000). https://pubmed.ncbi.nlm.nih.gov/10722724/ DOI: 10.1074/jbc.275.12.8794

tissue_or_cell_type

Serotonin acetylation

Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 175–186

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant enzyme substrate-specificity study · source_derived_draft · unverified_draft

### melatonin-aanat-serotonin Human AANAT transferred an acetyl group from acetyl-CoA to serotonin, producing N-acetylserotonin. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Serotonin is modified before it becomes melatonin. organism: Human AANAT expressed in bacteria tissue_or_cell_type: Serotonin acetylation experimental_model: Purified recombinant enzyme substrate-specificity study limitations: Biochemical mechanism, not evidence that dietary B5 or acetyl-CoA availability limits melatonin production in all humans. exposure: Serotonin and radiolabeled acetyl-CoA; product HPLC evidence_span: {"source_cache": "artifacts/melatonin-research/10722724.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7fb8418b17e92c5b3fed5d9c08afdb32f28c922dfe94274d3bb02b7e12b2b8c8", "start_char": 0, "end_char": 1857, "text_sha256": "7fb8418b17e92c5b3fed5d9c08afdb32f28c922dfe94274d3bb02b7e12b2b8c8"} [melatonin-p10722724] Substrate specificity and inhibition studies of human serotonin N-acetyltransferase. (2000). https://pubmed.ncbi.nlm.nih.gov/10722724/ DOI: 10.1074/jbc.275.12.8794

evidence_span

{"source_cache": "artifacts/chloride-research/21730057.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ef83bc710cfeb47a0815a2e11c431a5bb16a8927aa81eccc38b774c0dda454af", "start_char": 0, "end_char": 691, "text_sha256": "ef83bc710cfeb47a0815a2e11c431a5bb16a8927aa81eccc38b774c0dda454af"}

experimental_model

Mutagenesis, flux measurements and modeling

exposure

Asn101 substitutions and chloride-coupling assays

limitations

Transporter mechanism; no evidence that dietary chloride changes treat a mood disorder.

nutrient_topic

Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride

organism

Human SERT

plain_language

Chloride participates in neurotransmitter retrieval as well as in electrical signaling.

primary_references

[chloride-p21730057] A conserved asparagine residue in transmembrane segment 1 (TM1) of serotonin transporter dictates chloride-coupled neurotransmitter transport. (2011). https://pubmed.ncbi.nlm.nih.gov/21730057/ DOI: 10.1074/jbc.m111.250308

tissue_or_cell_type

Expressed membrane transporter

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 445–456

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mutagenesis, flux measurements and modeling · source_derived_draft · unverified_draft

### chloride-sert-chloride-coupling SERT Asn101 experiments linked chloride binding to concentrative serotonin uptake. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Chloride participates in neurotransmitter retrieval as well as in electrical signaling. organism: Human SERT tissue_or_cell_type: Expressed membrane transporter experimental_model: Mutagenesis, flux measurements and modeling limitations: Transporter mechanism; no evidence that dietary chloride changes treat a mood disorder. exposure: Asn101 substitutions and chloride-coupling assays evidence_span: {"source_cache": "artifacts/chloride-research/21730057.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ef83bc710cfeb47a0815a2e11c431a5bb16a8927aa81eccc38b774c0dda454af", "start_char": 0, "end_char": 691, "text_sha256": "ef83bc710cfeb47a0815a2e11c431a5bb16a8927aa81eccc38b774c0dda454af"} [chloride-p21730057] A conserved asparagine residue in transmembrane segment 1 (TM1) of serotonin transporter dictates chloride-coupled neurotransmitter transport. (2011). https://pubmed.ncbi.nlm.nih.gov/21730057/ DOI: 10.1074/jbc.m111.250308

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Rat pharmacological blockade.

limitations

Subunits and an exclusive linear pathway are not established by the accessed abstract.

nutrient_topic

Monosodium Glutamate (MSG) collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Monosodium L-glutamate

plain_language

A serotonin receptor relays part of the gut signal.

primary_references

Luminal amino acid sensing in the rat gastric mucosa. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16809638/ · DOI 10.1152/ajpgi.00587.2005

trigger_kind

machinery_impairment Imported condition classification; unverified.

Monosodium Glutamate (MSG): taste, gut sensing, exposure and cross-nutrient mechanisms (2026-09-20) · lines 162–168

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat pharmacological blockade. · source_derived_draft · unverified_draft

## monosodium-glutamate-5ht3-gate A serotonin receptor relays part of the gut signal. Blocking 5-HT3 receptors prevented the rat gastric vagal response to luminal glutamate. Model: Rat pharmacological blockade. Limitations: Subunits and an exclusive linear pathway are not established by the accessed abstract. Evidence access: Primary abstract Luminal amino acid sensing in the rat gastric mucosa. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16809638/ · DOI 10.1152/ajpgi.00587.2005

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Rat mucosal pharmacology.

limitations

Supports pathway ordering; not direct proof of each cell source or a human MSG–arginine interaction.

nutrient_topic

Monosodium Glutamate (MSG) collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Monosodium L-glutamate

plain_language

Nitric oxide and serotonin signaling interact upstream of the nerve response.

primary_references

Luminal amino acid sensing in the rat gastric mucosa. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16809638/ · DOI 10.1152/ajpgi.00587.2005

trigger_kind

machinery_impairment Imported condition classification; unverified.

Monosodium Glutamate (MSG): taste, gut sensing, exposure and cross-nutrient mechanisms (2026-09-20) · lines 170–176

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat mucosal pharmacology. · source_derived_draft · unverified_draft

## monosodium-glutamate-nos-gate Nitric oxide and serotonin signaling interact upstream of the nerve response. NOS inhibition blocked glutamate-evoked vagal firing; an NO donor mimicked firing and its response was blocked by 5-HT3 antagonism. Model: Rat mucosal pharmacology. Limitations: Supports pathway ordering; not direct proof of each cell source or a human MSG–arginine interaction. Evidence access: Primary abstract Luminal amino acid sensing in the rat gastric mucosa. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16809638/ · DOI 10.1152/ajpgi.00587.2005

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Mouse double knockout.

limitations

Viability and subtle behavioral findings prevent equating any serotonin reduction with one inevitable psychiatric syndrome.

nutrient_topic

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

plain_language

Removing both enzyme systems affected both compartments.

primary_references

Genetic disruption of both tryptophan hydroxylase genes dramatically reduces serotonin and affects behavior in models sensitive to antidepressants. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18923670/ · DOI 10.1371/journal.pone.0003301

trigger_kind

machinery_impairment Imported condition classification; unverified.

Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 138–144

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse double knockout. · source_derived_draft · unverified_draft

## tryptophan-tph-double-loss Removing both enzyme systems affected both compartments. Combined Tph1/Tph2 knockout reduced peripheral as well as central serotonin in mice. Model: Mouse double knockout. Limitations: Viability and subtle behavioral findings prevent equating any serotonin reduction with one inevitable psychiatric syndrome. Evidence access: Primary abstract Genetic disruption of both tryptophan hydroxylase genes dramatically reduces serotonin and affects behavior in models sensitive to antidepressants. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18923670/ · DOI 10.1371/journal.pone.0003301

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Mouse Tph2 knockout versus wild type.

limitations

Mouse developmental knockout is not a human dietary depletion experiment.

nutrient_topic

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

plain_language

The brain and peripheral serotonin factories are not interchangeable.

primary_references

Genetic disruption of both tryptophan hydroxylase genes dramatically reduces serotonin and affects behavior in models sensitive to antidepressants. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18923670/ · DOI 10.1371/journal.pone.0003301

trigger_kind

machinery_impairment Imported condition classification; unverified.

Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 130–136

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse Tph2 knockout versus wild type. · source_derived_draft · unverified_draft

## tryptophan-tph2-brain-loss The brain and peripheral serotonin factories are not interchangeable. Tph2 knockout markedly reduced mouse brain serotonin while peripheral serotonin was not substantially reduced. Model: Mouse Tph2 knockout versus wild type. Limitations: Mouse developmental knockout is not a human dietary depletion experiment. Evidence access: Primary abstract Genetic disruption of both tryptophan hydroxylase genes dramatically reduces serotonin and affects behavior in models sensitive to antidepressants. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18923670/ · DOI 10.1371/journal.pone.0003301

evidence_span

{"source_cache": "artifacts/paracetamol-research/18485596.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9bd927cbceffd6cf3a23e34bb0a6ce1584f989173a383745a97b82222f89798f", "start_char": 0, "end_char": 1545, "text_sha256": "9bd927cbceffd6cf3a23e34bb0a6ce1584f989173a383745a97b82222f89798f"}

experimental_model

Thermal, mechanical and chemical pain tests in cannabinoid receptor 1 knockout mice with receptor binding and pathway lesions

exposure

Acetaminophen with AM-251, cannabinoid receptor 1 deletion, fatty acid amide hydrolase inhibition and serotonergic pathway lesion

limitations

The binding experiment is what makes the receptor involvement indirect rather than direct, which is the substantive point. The proposed sequence is the authors’ synthesis.

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

Mouse

plain_language

The drug needs the cannabinoid receptor but never touches it, which is what a metabolite doing the work looks like.

primary_references

[apap-p18485596] Endocannabinoid and serotonergic systems are needed for acetaminophen-induced analgesia. (2008). https://pubmed.ncbi.nlm.nih.gov/18485596/ DOI: 10.1016/j.pain.2008.03.030

tissue_or_cell_type

Brain and spinal cord

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 337–348

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Thermal, mechanical and chemical pain tests in cannabinoid receptor 1 knockout mice with receptor binding and pathway lesions · source_derived_draft · unverified_draft

### apap-cb1-needed-but-not-bound In thermal, mechanical and chemical pain tests the specific cannabinoid receptor 1 antagonist AM-251 abolished the analgesic action of acetaminophen, which was also lost in cannabinoid receptor 1 knockout mice, yet acetaminophen was shown unable to bind to those receptors demonstrating an indirect involvement, inhibition of fatty acid amide hydrolase suppressed the effect, and the antinociceptive activity of a cannabinoid receptor 1 agonist was itself inhibited by lesion of bulbospinal serotonergic pathways and by spinal 5-HT receptor antagonists, leading the authors to propose a sequence of metabolism to AM404, indirect cannabinoid receptor involvement, reinforcement of serotonergic bulbospinal pathways and action at spinal serotonergic receptors. 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 drug needs the cannabinoid receptor but never touches it, which is what a metabolite doing the work looks like. organism: Mouse tissue_or_cell_type: Brain and spinal cord experimental_model: Thermal, mechanical and chemical pain tests in cannabinoid receptor 1 knockout mice with receptor binding and pathway lesions limitations: The binding experiment is what makes the receptor involvement indirect rather than direct, which is the substantive point. The proposed sequence is the authors’ synthesis. exposure: Acetaminophen with AM-251, cannabinoid receptor 1 deletion, fatty acid amide hydrolase inhibition and serotonergic pathway lesion evidence_span: {"source_cache": "artifacts/paracetamol-research/18485596.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9bd927cbceffd6cf3a23e34bb0a6ce1584f989173a383745a97b82222f89798f", "start_char": 0, "end_char": 1545, "text_sha256": "9bd927cbceffd6cf3a23e34bb0a6ce1584f989173a383745a97b82222f89798f"} [apap-p18485596] Endocannabinoid and serotonergic systems are needed for acetaminophen-induced analgesia. (2008). https://pubmed.ncbi.nlm.nih.gov/18485596/ DOI: 10.1016/j.pain.2008.03.030

evidence_access

Primary abstract

experimental_model

AANAT activity screen; substrate-site interaction proposed from docking.

limitations

Binding site and species are not independently established by the accessed abstract.

nutrient_topic

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

plain_language

A step on the serotonin-to-melatonin route can be inhibited.

primary_references

The flavonoid myricetin reduces nocturnal melatonin levels in the blood through the inhibition of serotonin N-acetyltransferase. · 2013 · https://pubmed.ncbi.nlm.nih.gov/24076393/ · DOI 10.1016/j.bbrc.2013.09.076

Myricetin: metabolism, immune signaling, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 564–570

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · AANAT activity screen; substrate-site interaction proposed from docking. · source_derived_draft · unverified_draft

## myricetin-aanat A step on the serotonin-to-melatonin route can be inhibited. Myricetin inhibited serotonin N-acetyltransferase activity in the reported enzyme assay. Model: AANAT activity screen; substrate-site interaction proposed from docking. Limitations: Binding site and species are not independently established by the accessed abstract. Evidence access: Primary abstract The flavonoid myricetin reduces nocturnal melatonin levels in the blood through the inhibition of serotonin N-acetyltransferase. · 2013 · https://pubmed.ncbi.nlm.nih.gov/24076393/ · DOI 10.1016/j.bbrc.2013.09.076

evidence_span

{"source_cache": "artifacts/theanine-research/9614715.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3ca01512b37779ba52ca0ebc23bcf73bb8c37df0756d8cf0c7d0a0de07e352a2", "start_char": 0, "end_char": 364, "text_sha256": "3ca01512b37779ba52ca0ebc23bcf73bb8c37df0756d8cf0c7d0a0de07e352a2"}

experimental_model

Brain monoamine assays and metabolism inhibitors

exposure

Theanine administration; inhibitor-based interpretation

limitations

Do not generalize to human mood or claim serotonin always rises. Decreased synthesis/increased degradation were proposed from inhibitor experiments.

nutrient_topic

L-Theanine research collection; topical membership is not evidence of a direct dietary effect. · L-Theanine

organism

Rats

plain_language

The direction was not the often-claimed universal increase in serotonin.

primary_references

[theanine-p9614715] Theanine-induced reduction of brain serotonin concentration in rats. (1998). https://pubmed.ncbi.nlm.nih.gov/9614715/ DOI: 10.1271/bbb.62.816

tissue_or_cell_type

Brain tryptophan and serotonin metabolism

L-Theanine: metabolism, neural signaling, nutrient connections and human outcomes (2026-09-17) · lines 406–417

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Brain monoamine assays and metabolism inhibitors · source_derived_draft · unverified_draft

### theanine-serotonin-decrease Brain serotonin and 5-HIAA decreased after theanine in this rat experiment. Condition category: normal nutrient_topic: L-Theanine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The direction was not the often-claimed universal increase in serotonin. organism: Rats tissue_or_cell_type: Brain tryptophan and serotonin metabolism experimental_model: Brain monoamine assays and metabolism inhibitors limitations: Do not generalize to human mood or claim serotonin always rises. Decreased synthesis/increased degradation were proposed from inhibitor experiments. exposure: Theanine administration; inhibitor-based interpretation evidence_span: {"source_cache": "artifacts/theanine-research/9614715.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3ca01512b37779ba52ca0ebc23bcf73bb8c37df0756d8cf0c7d0a0de07e352a2", "start_char": 0, "end_char": 364, "text_sha256": "3ca01512b37779ba52ca0ebc23bcf73bb8c37df0756d8cf0c7d0a0de07e352a2"} [theanine-p9614715] Theanine-induced reduction of brain serotonin concentration in rats. (1998). https://pubmed.ncbi.nlm.nih.gov/9614715/ DOI: 10.1271/bbb.62.816

evidence_span

{"source_cache": "artifacts/theanine-research/9614715.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3ca01512b37779ba52ca0ebc23bcf73bb8c37df0756d8cf0c7d0a0de07e352a2", "start_char": 0, "end_char": 364, "text_sha256": "3ca01512b37779ba52ca0ebc23bcf73bb8c37df0756d8cf0c7d0a0de07e352a2"}

experimental_model

Brain monoamine assays and metabolism inhibitors

exposure

Theanine administration; inhibitor-based interpretation

limitations

Do not generalize to human mood or claim serotonin always rises. Decreased synthesis/increased degradation were proposed from inhibitor experiments.

nutrient_topic

L-Theanine research collection; topical membership is not evidence of a direct dietary effect. · L-Theanine

organism

Rats

plain_language

More precursor does not guarantee more downstream neurotransmitter.

primary_references

[theanine-p9614715] Theanine-induced reduction of brain serotonin concentration in rats. (1998). https://pubmed.ncbi.nlm.nih.gov/9614715/ DOI: 10.1271/bbb.62.816

tissue_or_cell_type

Brain tryptophan and serotonin metabolism

L-Theanine: metabolism, neural signaling, nutrient connections and human outcomes (2026-09-17) · lines 419–430

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Brain monoamine assays and metabolism inhibitors · source_derived_draft · unverified_draft

### theanine-tryptophan-pool Brain tryptophan increased or tended to increase despite lower serotonin in the rat study. Condition category: normal nutrient_topic: L-Theanine research collection; topical membership is not evidence of a direct dietary effect. plain_language: More precursor does not guarantee more downstream neurotransmitter. organism: Rats tissue_or_cell_type: Brain tryptophan and serotonin metabolism experimental_model: Brain monoamine assays and metabolism inhibitors limitations: Do not generalize to human mood or claim serotonin always rises. Decreased synthesis/increased degradation were proposed from inhibitor experiments. exposure: Theanine administration; inhibitor-based interpretation evidence_span: {"source_cache": "artifacts/theanine-research/9614715.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3ca01512b37779ba52ca0ebc23bcf73bb8c37df0756d8cf0c7d0a0de07e352a2", "start_char": 0, "end_char": 364, "text_sha256": "3ca01512b37779ba52ca0ebc23bcf73bb8c37df0756d8cf0c7d0a0de07e352a2"} [theanine-p9614715] Theanine-induced reduction of brain serotonin concentration in rats. (1998). https://pubmed.ncbi.nlm.nih.gov/9614715/ DOI: 10.1271/bbb.62.816

evidence_span

{"source_cache": "artifacts/acetate-research/16453106.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "14165574bceda6c6197de30baae79895b87d2b95272ea42c231554d7a4c015d2", "start_char": 0, "end_char": 1605, "text_sha256": "14165574bceda6c6197de30baae79895b87d2b95272ea42c231554d7a4c015d2"}

experimental_model

RT-PCR, Western blotting and immunohistochemistry with a rat-specific GPR43 antiserum

exposure

Receptor localisation across mucosal cell types

limitations

An anatomical result naming the cells that carry the receptor. Localisation is not function, and the antiserum was raised against a synthesised fragment.

nutrient_topic

Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion. · Acetic acid

organism

Rat

plain_language

The receptor sits on the gut cells that make PYY, and on mast cells, but not on the serotonin-making gut cells.

primary_references

[acetate-p16453106] Short-chain fatty acid receptor, GPR43, is expressed by enteroendocrine cells and mucosal mast cells in rat intestine. (2006). https://pubmed.ncbi.nlm.nih.gov/16453106/ DOI: 10.1007/s00441-005-0140-x

tissue_or_cell_type

Distal ileum and colon

Acetic acid: the ingested acid, the receptors acetate binds, the acetyl-CoA it becomes, and the acetyl groups that reach histones (2026-09-21) · lines 277–288

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · RT-PCR, Western blotting and immunohistochemistry with a rat-specific GPR43 antiserum · source_derived_draft · unverified_draft

### acetate-ffar2-on-pyy-cells GPR43 immunoreactivity was localised to enteroendocrine cells expressing peptide YY, whereas 5-hydroxytryptamine-immunoreactive enteroendocrine cells were not immunoreactive for GPR43, and mast cells of the lamina propria expressing 5-hydroxytryptamine were also GPR43-immunoreactive. Condition category: normal nutrient_topic: Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion. plain_language: The receptor sits on the gut cells that make PYY, and on mast cells, but not on the serotonin-making gut cells. organism: Rat tissue_or_cell_type: Distal ileum and colon experimental_model: RT-PCR, Western blotting and immunohistochemistry with a rat-specific GPR43 antiserum limitations: An anatomical result naming the cells that carry the receptor. Localisation is not function, and the antiserum was raised against a synthesised fragment. exposure: Receptor localisation across mucosal cell types evidence_span: {"source_cache": "artifacts/acetate-research/16453106.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "14165574bceda6c6197de30baae79895b87d2b95272ea42c231554d7a4c015d2", "start_char": 0, "end_char": 1605, "text_sha256": "14165574bceda6c6197de30baae79895b87d2b95272ea42c231554d7a4c015d2"} [acetate-p16453106] Short-chain fatty acid receptor, GPR43, is expressed by enteroendocrine cells and mucosal mast cells in rat intestine. (2006). https://pubmed.ncbi.nlm.nih.gov/16453106/ DOI: 10.1007/s00441-005-0140-x

evidence_span

{"source_cache": "artifacts/cold-research/12546194.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "08c39cf0438d2f97c989e86721085415de696a3c7df99f5c2dc6529c40f7aeb2", "start_char": 0, "end_char": 1785, "text_sha256": "08c39cf0438d2f97c989e86721085415de696a3c7df99f5c2dc6529c40f7aeb2"}

experimental_model

Follow-up of winter swimmers and non-swimmer controls sampled in autumn, winter and spring

exposure

One winter swimming season

limitations

A seasonal follow-up with a control group. Its negative conclusion is explicit: the changes seen in swimmers also occurred in controls.

nutrient_topic

Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Cold water immersion

organism

Human

plain_language

Across a whole season the swimmers changed no more than the people who stayed dry.

primary_references

[cold-p12546194] Plasma catecholamines, serotonin and their metabolites and beta-endorphin of winter swimmers during one winter. Possible correlations to psychological traits. (2002). https://pubmed.ncbi.nlm.nih.gov/12546194/ DOI: 10.3402/ijch.v61i4.17494

tissue_or_cell_type

Plasma hormones and blood pressure

Cold water immersion: cold sensing, heat production, the catecholamine axis and what repeated exposure changes (2026-09-19) · lines 663–674

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Follow-up of winter swimmers and non-swimmer controls sampled in autumn, winter and spring · source_derived_draft · unverified_draft

### cold-seasonal-catecholamine-fall Mean plasma noradrenaline fell significantly from autumn to spring and more so in winter swimmers, but with no statistically significant difference between swimmers and controls; systolic blood pressure fell in swimmers, and plasma homovanillic acid and beta-endorphin were unchanged across all seasonal samples in both groups. Condition category: normal nutrient_topic: Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Across a whole season the swimmers changed no more than the people who stayed dry. organism: Human tissue_or_cell_type: Plasma hormones and blood pressure experimental_model: Follow-up of winter swimmers and non-swimmer controls sampled in autumn, winter and spring limitations: A seasonal follow-up with a control group. Its negative conclusion is explicit: the changes seen in swimmers also occurred in controls. exposure: One winter swimming season evidence_span: {"source_cache": "artifacts/cold-research/12546194.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "08c39cf0438d2f97c989e86721085415de696a3c7df99f5c2dc6529c40f7aeb2", "start_char": 0, "end_char": 1785, "text_sha256": "08c39cf0438d2f97c989e86721085415de696a3c7df99f5c2dc6529c40f7aeb2"} [cold-p12546194] Plasma catecholamines, serotonin and their metabolites and beta-endorphin of winter swimmers during one winter. Possible correlations to psychological traits. (2002). https://pubmed.ncbi.nlm.nih.gov/12546194/ DOI: 10.3402/ijch.v61i4.17494

dose

300 mL of 10% w/v sucrose with or without 60 ppm lactisole; parallel glucose conditions

duration

120 minutes; breakfast at 2 hours

evidence_access

Primary full-text methods/results and metadata inspected.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

27 healthy men in randomized single-blinded crossover

exposure_scope

Sucrose and taste antagonist

limitations

Acute experiment in men; peripheral serotonin is not brain serotonin. Receptor mediation and binding-affinity explanation were not directly established; no long-term weight outcome.

nutrient_topic

Sucrose chapter; direct sucrose observations are distinguished from shared component metabolism. · Sucrose

organism

27 healthy men in randomized single-blinded crossover

plain_language

Adding lactisole to sucrose lowered the plasma serotonin change at 30 minutes relative to sucrose alone.

primary_references

Sweet Taste Antagonist Lactisole Administered in Combination with Sucrose, But Not Glucose, Increases Energy Intake and Decreases Peripheral Serotonin in Male Subjects. (2020). https://pubmed.ncbi.nlm.nih.gov/33066498/ DOI: 10.3390/nu12103133

route

Oral test drink after overnight fast

tissue

Subsequent food intake and peripheral hormone measurements

Sucrose: mechanism of action and metabolic impact (2026-09-20) · lines 127–137

Original AI-assisted source-specific sucrose curation with shared canonical claims retained by identity. Primary-study citations, negative findings, exposure details and limitations preserved. Not publisher full text. · supports · 27 healthy men in randomized single-blinded crossover · source_derived_draft · unverified_draft

## sucrose-lactisole-serotonin Adding lactisole to sucrose lowered the plasma serotonin change at 30 minutes relative to sucrose alone. Model/species: 27 healthy men in randomized single-blinded crossover Tissue: Subsequent food intake and peripheral hormone measurements Exposure: 300 mL of 10% w/v sucrose with or without 60 ppm lactisole; parallel glucose conditions Route: Oral test drink after overnight fast Duration: 120 minutes; breakfast at 2 hours Exposure scope: Sucrose and taste antagonist Limits: Acute experiment in men; peripheral serotonin is not brain serotonin. Receptor mediation and binding-affinity explanation were not directly established; no long-term weight outcome. Reference: Sweet Taste Antagonist Lactisole Administered in Combination with Sucrose, But Not Glucose, Increases Energy Intake and Decreases Peripheral Serotonin in Male Subjects. (2020). https://pubmed.ncbi.nlm.nih.gov/33066498/ DOI: 10.3390/nu12103133 Access: Primary full-text methods/results and metadata inspected.

dose

Concentration-dependent gingerol application; exact range not in accessed abstract

duration

Not specified in accessed abstract

evidence_access

Primary PubMed abstract.

evidence_scope

literature_reviewed; model-specific source-derived curation, not universally established human effects

experimental_model

Mouse N1E-115 neuroblastoma cells

limitations

Cation flux is a functional assay, not a demonstrated orthosteric binding site or clinical antiemetic response.

nutrient_topic

Gingerols collection; each molecular form and experimental preparation remains explicit. · Gingerols

organism

Mouse N1E-115 neuroblastoma cells

plain_language

10-Gingerol inhibited 5-HT3-mediated cation influx in N1E-115 cells.

primary_references

Mode of action of gingerols and shogaols on 5-HT3 receptors: binding studies, cation uptake by the receptor channel and contraction of isolated guinea-pig ileum. (2006). https://pubmed.ncbi.nlm.nih.gov/16364290/ DOI: 10.1016/j.ejphar.2005.10.049

route

In vitro addition

tissue

Native 5-HT3 receptor-channel complex

Gingerols: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 118–127

Original AI-assisted curation of thirteen primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Mouse N1E-115 neuroblastoma cells · source_derived_draft · unverified_draft

## gingerols-10-5ht3-flux 10-Gingerol inhibited 5-HT3-mediated cation influx in N1E-115 cells. Model/species: Mouse N1E-115 neuroblastoma cells Tissue: Native 5-HT3 receptor-channel complex Exposure: Concentration-dependent gingerol application; exact range not in accessed abstract Route: In vitro addition Duration: Not specified in accessed abstract Limits: Cation flux is a functional assay, not a demonstrated orthosteric binding site or clinical antiemetic response. Primary reference: Mode of action of gingerols and shogaols on 5-HT3 receptors: binding studies, cation uptake by the receptor channel and contraction of isolated guinea-pig ileum. (2006). https://pubmed.ncbi.nlm.nih.gov/16364290/ DOI: 10.1016/j.ejphar.2005.10.049 Access: Primary PubMed abstract.

dose

Concentration-dependent gingerol application; exact range not in accessed abstract

duration

Not specified in accessed abstract

evidence_access

Primary PubMed abstract.

evidence_scope

literature_reviewed; model-specific source-derived curation, not universally established human effects

experimental_model

Mouse N1E-115 neuroblastoma cells

limitations

Cation flux is a functional assay, not a demonstrated orthosteric binding site or clinical antiemetic response.

nutrient_topic

Gingerols collection; each molecular form and experimental preparation remains explicit. · Gingerols

organism

Mouse N1E-115 neuroblastoma cells

plain_language

6-Gingerol inhibited 5-HT3-mediated cation influx in N1E-115 cells.

primary_references

Mode of action of gingerols and shogaols on 5-HT3 receptors: binding studies, cation uptake by the receptor channel and contraction of isolated guinea-pig ileum. (2006). https://pubmed.ncbi.nlm.nih.gov/16364290/ DOI: 10.1016/j.ejphar.2005.10.049

route

In vitro addition

tissue

Native 5-HT3 receptor-channel complex

Gingerols: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 52–61

Original AI-assisted curation of thirteen primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Mouse N1E-115 neuroblastoma cells · source_derived_draft · unverified_draft

## gingerols-6-5ht3-flux 6-Gingerol inhibited 5-HT3-mediated cation influx in N1E-115 cells. Model/species: Mouse N1E-115 neuroblastoma cells Tissue: Native 5-HT3 receptor-channel complex Exposure: Concentration-dependent gingerol application; exact range not in accessed abstract Route: In vitro addition Duration: Not specified in accessed abstract Limits: Cation flux is a functional assay, not a demonstrated orthosteric binding site or clinical antiemetic response. Primary reference: Mode of action of gingerols and shogaols on 5-HT3 receptors: binding studies, cation uptake by the receptor channel and contraction of isolated guinea-pig ileum. (2006). https://pubmed.ncbi.nlm.nih.gov/16364290/ DOI: 10.1016/j.ejphar.2005.10.049 Access: Primary PubMed abstract.

dose

6-Gingerol 50 or 100 mg/kg twice; cisplatin 6 mg/kg once, 1 h after first gingerol dose

duration

Gingerol at 07:00 and 19:00; assessment 24 h after cisplatin

evidence_access

Primary PubMed abstract.

evidence_scope

literature_reviewed; model-specific source-derived curation, not universally established human effects

experimental_model

Rats in a cisplatin-induced pica model

limitations

Rats do not vomit; pica is a surrogate. This experiment does not establish human antiemetic efficacy or preserved anticancer efficacy.

nutrient_topic

Gingerols collection; each molecular form and experimental preparation remains explicit. · Gingerols

organism

Rats in a cisplatin-induced pica model

plain_language

6-Gingerol treatment attenuated the cisplatin-associated rise in measured serotonin in rats.

primary_references

[6]-Gingerol Ameliorates Cisplatin-Induced Pica by Regulating the TPH/MAO-A/SERT/5-HT/5-HT3 Receptor System in Rats. (2020). https://pubmed.ncbi.nlm.nih.gov/33061309/ DOI: 10.2147/DDDT.S270185

route

Gingerol gavage; cisplatin intraperitoneal injection

tissue

Kaolin intake, ileum, medulla oblongata and serum

Gingerols: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 547–556

Original AI-assisted curation of thirteen primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Rats in a cisplatin-induced pica model · source_derived_draft · unverified_draft

## gingerols-6-cisplatin-serotonin 6-Gingerol treatment attenuated the cisplatin-associated rise in measured serotonin in rats. Model/species: Rats in a cisplatin-induced pica model Tissue: Kaolin intake, ileum, medulla oblongata and serum Exposure: 6-Gingerol 50 or 100 mg/kg twice; cisplatin 6 mg/kg once, 1 h after first gingerol dose Route: Gingerol gavage; cisplatin intraperitoneal injection Duration: Gingerol at 07:00 and 19:00; assessment 24 h after cisplatin Limits: Rats do not vomit; pica is a surrogate. This experiment does not establish human antiemetic efficacy or preserved anticancer efficacy. Primary reference: [6]-Gingerol Ameliorates Cisplatin-Induced Pica by Regulating the TPH/MAO-A/SERT/5-HT/5-HT3 Receptor System in Rats. (2020). https://pubmed.ncbi.nlm.nih.gov/33061309/ DOI: 10.2147/DDDT.S270185 Access: Primary PubMed abstract.

dose

Concentration-dependent gingerol application; exact range not in accessed abstract

duration

Not specified in accessed abstract

evidence_access

Primary PubMed abstract.

evidence_scope

literature_reviewed; model-specific source-derived curation, not universally established human effects

experimental_model

Mouse N1E-115 neuroblastoma cells

limitations

Cation flux is a functional assay, not a demonstrated orthosteric binding site or clinical antiemetic response.

nutrient_topic

Gingerols collection; each molecular form and experimental preparation remains explicit. · Gingerols

organism

Mouse N1E-115 neuroblastoma cells

plain_language

8-Gingerol inhibited 5-HT3-mediated cation influx in N1E-115 cells.

primary_references

Mode of action of gingerols and shogaols on 5-HT3 receptors: binding studies, cation uptake by the receptor channel and contraction of isolated guinea-pig ileum. (2006). https://pubmed.ncbi.nlm.nih.gov/16364290/ DOI: 10.1016/j.ejphar.2005.10.049

route

In vitro addition

tissue

Native 5-HT3 receptor-channel complex

Gingerols: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 85–94

Original AI-assisted curation of thirteen primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Mouse N1E-115 neuroblastoma cells · source_derived_draft · unverified_draft

## gingerols-8-5ht3-flux 8-Gingerol inhibited 5-HT3-mediated cation influx in N1E-115 cells. Model/species: Mouse N1E-115 neuroblastoma cells Tissue: Native 5-HT3 receptor-channel complex Exposure: Concentration-dependent gingerol application; exact range not in accessed abstract Route: In vitro addition Duration: Not specified in accessed abstract Limits: Cation flux is a functional assay, not a demonstrated orthosteric binding site or clinical antiemetic response. Primary reference: Mode of action of gingerols and shogaols on 5-HT3 receptors: binding studies, cation uptake by the receptor channel and contraction of isolated guinea-pig ileum. (2006). https://pubmed.ncbi.nlm.nih.gov/16364290/ DOI: 10.1016/j.ejphar.2005.10.049 Access: Primary PubMed abstract.