Phosphoinositide 3-kinase family

experimental_model

Biochemical kinase assays plus MDA-MB-231 and A549 cell experiments.

limitations

PI3K isoform is not assigned from abstract; docking is a model, not a solved ligand structure.

nutrient_topic

EGCG collection; comparator and shared-pathway records retain their actual intervention. · Epigallocatechin-3-gallate (EGCG)

plain_language

EGCG competed with the enzyme’s energy substrate.

primary_references

Epigallocatechin gallate (EGCG), a major component of green tea, is a dual phosphoinositide-3-kinase/mTOR inhibitor. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21300025/ · DOI 10.1016/j.bbrc.2011.02.010

EGCG: receptor signaling, metabolism, nutrient interactions and discovery questions (2026-09-18) · lines 212–218

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Biochemical kinase assays plus MDA-MB-231 and A549 cell experiments. · source_derived_draft · unverified_draft

## egcg-pi3k EGCG competed with the enzyme’s energy substrate. EGCG showed ATP-competitive inhibition with Ki 380 nanomolar in the reported enzyme assay. Model: Biochemical kinase assays plus MDA-MB-231 and A549 cell experiments. Limitations: PI3K isoform is not assigned from abstract; docking is a model, not a solved ligand structure. Evidence access: primary abstract. Epigallocatechin gallate (EGCG), a major component of green tea, is a dual phosphoinositide-3-kinase/mTOR inhibitor. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21300025/ · DOI 10.1016/j.bbrc.2011.02.010

cross_nutrient

Insulin -> magnesium-channel trafficking; complements the separate Mg -> insulin-response findings.

experimental_model

Expression-cell electrophysiology and surface fluorescence.

limitations

Combined pathway perturbations; no unspecified PI3K isoform assigned and no universal clinical feedback loop proven.

nutrient_topic

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

organism

Homo sapiens

plain_language

Insulin can affect the magnesium entry machinery as well as glucose metabolism.

primary_references

[mg-nair2012] Loss of insulin-induced activation of TRPM6 magnesium channels results in impaired glucose tolerance during pregnancy (2012). https://pubmed.ncbi.nlm.nih.gov/22733750/ DOI: 10.1073/pnas.1113811109

tissue_or_cell_type

TRPM6-expressing cells; plasma membrane

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1527–1537

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Expression-cell electrophysiology and surface fluorescence. · source_derived_draft · unverified_draft

### mg-insulin-trpm6-surface-regulation Insulin increased TRPM6 surface abundance and channel activity through a PI3K- and RAC1-dependent pathway. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Insulin can affect the magnesium entry machinery as well as glucose metabolism. organism: Homo sapiens tissue_or_cell_type: TRPM6-expressing cells; plasma membrane experimental_model: Expression-cell electrophysiology and surface fluorescence. limitations: Combined pathway perturbations; no unspecified PI3K isoform assigned and no universal clinical feedback loop proven. cross_nutrient: Insulin -> magnesium-channel trafficking; complements the separate Mg -> insulin-response findings. [mg-nair2012] Loss of insulin-induced activation of TRPM6 magnesium channels results in impaired glucose tolerance during pregnancy (2012). https://pubmed.ncbi.nlm.nih.gov/22733750/ DOI: 10.1073/pnas.1113811109

dose

Eugenol around the effective 2-micromolar range

duration

Acute

evidence_access

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

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Washed human platelets

limitations

Pathway suppression does not identify one direct binding target and must not be generalized to every platelet agonist.

nutrient_topic

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

organism

Washed human platelets

plain_language

Eugenol suppressed collagen-induced PLC-gamma2/PKC, PI3K/Akt/GSK3beta, MAPK and cPLA2/thromboxane-A2 signaling in human platelets.

primary_references

Eugenol Suppresses Platelet Activation and Mitigates Pulmonary Thromboembolism in Humans and Murine Models. (2024). https://pubmed.ncbi.nlm.nih.gov/38396774/ DOI: 10.3390/ijms25042098

route

In vitro

tissue

Signal phosphorylation, ATP release, P-selectin and calcium

Eugenol: mechanism of action and interactions (2026-09-20) · lines 22–31

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Washed human platelets · source_derived_draft · unverified_draft

## eugenol-platelet-pathways Eugenol suppressed collagen-induced PLC-gamma2/PKC, PI3K/Akt/GSK3beta, MAPK and cPLA2/thromboxane-A2 signaling in human platelets. Model/species: Washed human platelets Tissue/system: Signal phosphorylation, ATP release, P-selectin and calcium Exposure: Eugenol around the effective 2-micromolar range Route: In vitro Duration: Acute Limits: Pathway suppression does not identify one direct binding target and must not be generalized to every platelet agonist. Primary reference: Eugenol Suppresses Platelet Activation and Mitigates Pulmonary Thromboembolism in Humans and Murine Models. (2024). https://pubmed.ncbi.nlm.nih.gov/38396774/ DOI: 10.3390/ijms25042098 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

dose

Erinacine C with genetic and pharmacological inhibitors

duration

Differentiation assay

evidence_access

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

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

PC12 cells and astrocytic reporter cells

limitations

The study supports pathway involvement but not direct binding, human exposure, or a clinical neuroregenerative effect.

nutrient_topic

Hericenones & Erinacines chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Hericenones and erinacines

organism

PC12 cells and astrocytic reporter cells

plain_language

Erinacine C induced PC12 differentiation through TrkA and associated PLC-gamma, PI3K and ERK pathways.

primary_references

Erinacine C Activates Transcription from a Consensus ETS DNA Binding Site in Astrocytic Cells in Addition to NGF Induction. (2020). https://pubmed.ncbi.nlm.nih.gov/33066380/ DOI: 10.3390/biom10101440

route

In vitro

tissue

Neurotrophin-dependent differentiation

Hericenones & Erinacines: mechanism of action and interactions (2026-09-20) · lines 88–97

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · PC12 cells and astrocytic reporter cells · source_derived_draft · unverified_draft

## hericenones-erinacines-erinacine-c-trka Erinacine C induced PC12 differentiation through TrkA and associated PLC-gamma, PI3K and ERK pathways. Model/species: PC12 cells and astrocytic reporter cells Tissue/system: Neurotrophin-dependent differentiation Exposure: Erinacine C with genetic and pharmacological inhibitors Route: In vitro Duration: Differentiation assay Limits: The study supports pathway involvement but not direct binding, human exposure, or a clinical neuroregenerative effect. Primary reference: Erinacine C Activates Transcription from a Consensus ETS DNA Binding Site in Astrocytic Cells in Addition to NGF Induction. (2020). https://pubmed.ncbi.nlm.nih.gov/33066380/ DOI: 10.3390/biom10101440 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_span

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experimental_model

Cell challenge with siRNA and pathway inhibitors

exposure

Zeaxanthin commonly 10 micromolar for 24 h; 300 micromolar t-BHP challenge for 6 h; study-specific inhibitors

limitations

Pharmacological cell exposures are not dietary concentrations. PI3K/Akt inhibitor evidence is not direct zeaxanthin binding to a kinase. Liposome GSTP1 protection and this cellular GSH-dependent response are different mechanisms.

nutrient_topic

Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin

organism

Human ARPE-19 cell line

plain_language

Activating a pathway and needing it for protection are different tests.

primary_references

[zeaxanthin-p24810054] Zeaxanthin induces Nrf2-mediated phase II enzymes in protection of cell death. (2014). https://pubmed.ncbi.nlm.nih.gov/24810054/ DOI: 10.1038/cddis.2014.190

tissue_or_cell_type

Retinal pigment epithelial model

Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 470–481

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell challenge with siRNA and pathway inhibitors · source_derived_draft · unverified_draft

### zeaxanthin-pi3k-block LY294002 blocked zeaxanthin-associated survival protection; U0126 did not show the same effect. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Activating a pathway and needing it for protection are different tests. organism: Human ARPE-19 cell line tissue_or_cell_type: Retinal pigment epithelial model experimental_model: Cell challenge with siRNA and pathway inhibitors limitations: Pharmacological cell exposures are not dietary concentrations. PI3K/Akt inhibitor evidence is not direct zeaxanthin binding to a kinase. Liposome GSTP1 protection and this cellular GSH-dependent response are different mechanisms. exposure: Zeaxanthin commonly 10 micromolar for 24 h; 300 micromolar t-BHP challenge for 6 h; study-specific inhibitors evidence_span: {"source_cache": "artifacts/zeaxanthin-research/24810054.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f185c805dd5d825445cb40e547b794fbc595388aff6e2d29ac81c2eab8b8348", "start_char": 5813, "end_char": 15716, "text_sha256": "89e6abf1967c10b359cb62d935d5b839cf53acf42576d9db3d463bff9f474e38"} [zeaxanthin-p24810054] Zeaxanthin induces Nrf2-mediated phase II enzymes in protection of cell death. (2014). https://pubmed.ncbi.nlm.nih.gov/24810054/ DOI: 10.1038/cddis.2014.190

experimental_model

MDA-MB-231 and A549 cells.

limitations

A pathway readout does not establish a unique causal target or human anticancer efficacy.

nutrient_topic

EGCG collection; comparator and shared-pathway records retain their actual intervention. · Epigallocatechin-3-gallate (EGCG)

plain_language

Downstream growth signaling changed in the cell experiments.

primary_references

Epigallocatechin gallate (EGCG), a major component of green tea, is a dual phosphoinositide-3-kinase/mTOR inhibitor. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21300025/ · DOI 10.1016/j.bbrc.2011.02.010

EGCG: receptor signaling, metabolism, nutrient interactions and discovery questions (2026-09-18) · lines 228–234

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · MDA-MB-231 and A549 cells. · source_derived_draft · unverified_draft

## egcg-akt Downstream growth signaling changed in the cell experiments. EGCG reduced AKT Ser473 phosphorylation alongside proliferation in the tested cancer cells. Model: MDA-MB-231 and A549 cells. Limitations: A pathway readout does not establish a unique causal target or human anticancer efficacy. Evidence access: primary abstract. Epigallocatechin gallate (EGCG), a major component of green tea, is a dual phosphoinositide-3-kinase/mTOR inhibitor. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21300025/ · DOI 10.1016/j.bbrc.2011.02.010