Indicaxanthin

dose

Indicaxanthin 10, 50 and 100 micromolar

duration

48 h

evidence_access

Primary open full text, relevant results/methods and PubMed metadata.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human Caco-2 colorectal cancer cells

limitations

Marker abundance and acidic organelles are not sufficient alone to quantify complete autophagic flux. Predicted BCL2 binding remains computational; methylation associations do not prove causation. The protein response was not monotonic across the tested concentrations.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Human Caco-2 colorectal cancer cells

plain_language

Indicaxanthin at 50 micromolar increased Beclin1 protein abundance in Caco-2 cells.

primary_references

Indicaxanthin Induces Autophagy in Intestinal Epithelial Cancer Cells by Epigenetic Mechanisms Involving DNA Methylation. (2023). https://pubmed.ncbi.nlm.nih.gov/37571432/ DOI: 10.3390/nu15153495

route

In vitro addition

tissue

Autophagy markers and DNA methylome

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 426–435

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Human Caco-2 colorectal cancer cells · source_derived_draft · unverified_draft

## indicaxanthin-autophagy-becn1 Indicaxanthin at 50 micromolar increased Beclin1 protein abundance in Caco-2 cells. Model/species: Human Caco-2 colorectal cancer cells Tissue: Autophagy markers and DNA methylome Exposure: Indicaxanthin 10, 50 and 100 micromolar Route: In vitro addition Duration: 48 h Limits: Marker abundance and acidic organelles are not sufficient alone to quantify complete autophagic flux. Predicted BCL2 binding remains computational; methylation associations do not prove causation. The protein response was not monotonic across the tested concentrations. Primary reference: Indicaxanthin Induces Autophagy in Intestinal Epithelial Cancer Cells by Epigenetic Mechanisms Involving DNA Methylation. (2023). https://pubmed.ncbi.nlm.nih.gov/37571432/ DOI: 10.3390/nu15153495 Access: Primary open full text, relevant results/methods and PubMed metadata.

dose

Indicaxanthin 10, 50 and 100 micromolar

duration

48 h

evidence_access

Primary open full text, relevant results/methods and PubMed metadata.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human Caco-2 colorectal cancer cells

limitations

Marker abundance and acidic organelles are not sufficient alone to quantify complete autophagic flux. Predicted BCL2 binding remains computational; methylation associations do not prove causation.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Human Caco-2 colorectal cancer cells

plain_language

Indicaxanthin treatment increased the LC3-II marker in Caco-2 cells.

primary_references

Indicaxanthin Induces Autophagy in Intestinal Epithelial Cancer Cells by Epigenetic Mechanisms Involving DNA Methylation. (2023). https://pubmed.ncbi.nlm.nih.gov/37571432/ DOI: 10.3390/nu15153495

route

In vitro addition

tissue

Autophagy markers and DNA methylome

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 415–424

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Human Caco-2 colorectal cancer cells · source_derived_draft · unverified_draft

## indicaxanthin-autophagy-lc3 Indicaxanthin treatment increased the LC3-II marker in Caco-2 cells. Model/species: Human Caco-2 colorectal cancer cells Tissue: Autophagy markers and DNA methylome Exposure: Indicaxanthin 10, 50 and 100 micromolar Route: In vitro addition Duration: 48 h Limits: Marker abundance and acidic organelles are not sufficient alone to quantify complete autophagic flux. Predicted BCL2 binding remains computational; methylation associations do not prove causation. Primary reference: Indicaxanthin Induces Autophagy in Intestinal Epithelial Cancer Cells by Epigenetic Mechanisms Involving DNA Methylation. (2023). https://pubmed.ncbi.nlm.nih.gov/37571432/ DOI: 10.3390/nu15153495 Access: Primary open full text, relevant results/methods and PubMed metadata.

dose

Indicaxanthin 10, 50 and 100 micromolar

duration

48 h

evidence_access

Primary open full text, relevant results/methods and PubMed metadata.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human Caco-2 colorectal cancer cells

limitations

Marker abundance and acidic organelles are not sufficient alone to quantify complete autophagic flux. Predicted BCL2 binding remains computational; methylation associations do not prove causation.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Human Caco-2 colorectal cancer cells

plain_language

Indicaxanthin at 50 or 100 micromolar increased acidic-vesicle fluorescence in Caco-2 cells.

primary_references

Indicaxanthin Induces Autophagy in Intestinal Epithelial Cancer Cells by Epigenetic Mechanisms Involving DNA Methylation. (2023). https://pubmed.ncbi.nlm.nih.gov/37571432/ DOI: 10.3390/nu15153495

route

In vitro addition

tissue

Autophagy markers and DNA methylome

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 437–446

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Human Caco-2 colorectal cancer cells · source_derived_draft · unverified_draft

## indicaxanthin-autophagy-organelles Indicaxanthin at 50 or 100 micromolar increased acidic-vesicle fluorescence in Caco-2 cells. Model/species: Human Caco-2 colorectal cancer cells Tissue: Autophagy markers and DNA methylome Exposure: Indicaxanthin 10, 50 and 100 micromolar Route: In vitro addition Duration: 48 h Limits: Marker abundance and acidic organelles are not sufficient alone to quantify complete autophagic flux. Predicted BCL2 binding remains computational; methylation associations do not prove causation. Primary reference: Indicaxanthin Induces Autophagy in Intestinal Epithelial Cancer Cells by Epigenetic Mechanisms Involving DNA Methylation. (2023). https://pubmed.ncbi.nlm.nih.gov/37571432/ DOI: 10.3390/nu15153495 Access: Primary open full text, relevant results/methods and PubMed metadata.

dose

Purified indicaxanthin; growth IC50 115 +/- 15 micromolar, exact exposure series not in accessed abstract

duration

Exposure duration not specified in the accessed primary abstract

evidence_access

Primary PubMed abstract.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Proliferating human Caco-2 colorectal cancer cells

limitations

Locus-specific demethylation does not imply universal DNA demethylation. A cell-line response is not cancer prevention in people.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Proliferating human Caco-2 colorectal cancer cells

plain_language

Purified indicaxanthin inhibited proliferating Caco-2-cell growth, with a reported IC50 of 115 +/- 15 micromolar.

primary_references

Anti-proliferative and pro-apoptotic activity of whole extract and isolated indicaxanthin from Opuntia ficus-indica associated with re-activation of the onco-suppressor p16(INK4a) gene in human colorectal carcinoma (Caco-2) cells. (2014). https://pubmed.ncbi.nlm.nih.gov/24937448/ DOI: 10.1016/j.bbrc.2014.06.029

route

In vitro addition

tissue

Epigenetic and growth assays

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 404–413

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Proliferating human Caco-2 colorectal cancer cells · source_derived_draft · unverified_draft

## indicaxanthin-caco2-growth Purified indicaxanthin inhibited proliferating Caco-2-cell growth, with a reported IC50 of 115 +/- 15 micromolar. Model/species: Proliferating human Caco-2 colorectal cancer cells Tissue: Epigenetic and growth assays Exposure: Purified indicaxanthin; growth IC50 115 +/- 15 micromolar, exact exposure series not in accessed abstract Route: In vitro addition Duration: Exposure duration not specified in the accessed primary abstract Limits: Locus-specific demethylation does not imply universal DNA demethylation. A cell-line response is not cancer prevention in people. Primary reference: Anti-proliferative and pro-apoptotic activity of whole extract and isolated indicaxanthin from Opuntia ficus-indica associated with re-activation of the onco-suppressor p16(INK4a) gene in human colorectal carcinoma (Caco-2) cells. (2014). https://pubmed.ncbi.nlm.nih.gov/24937448/ DOI: 10.1016/j.bbrc.2014.06.029 Access: Primary PubMed abstract.

dose

Dietary-consistent pigment concentrations, exact range not in accessed abstract; pH 6.0/7.4 gradient

duration

Time-course assay; exact interval not in accessed abstract

evidence_access

Primary PubMed abstract.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human Caco-2 epithelial monolayers on Transwell inserts

limitations

Cell permeability is not a human absorption fraction. MRP2-mediated efflux in this paper concerns betanin, not indicaxanthin. Different protocols limit comparison with the 2022 transport paper. A paracellular contribution is supported; no specific transporter is assigned.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Human Caco-2 epithelial monolayers on Transwell inserts

plain_language

Indicaxanthin transport was non-polarized and insensitive to the tested transporter inhibitors; EDTA treatment increased its passage.

primary_references

Trans-epithelial transport of the betalain pigments indicaxanthin and betanin across Caco-2 cell monolayers and influence of food matrix. (2013). https://pubmed.ncbi.nlm.nih.gov/22806766/ DOI: 10.1007/s00394-012-0414-5

route

In vitro transepithelial transport

tissue

Apical/basolateral compartments

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 74–83

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Human Caco-2 epithelial monolayers on Transwell inserts · source_derived_draft · unverified_draft

## indicaxanthin-caco2-passive-transport Indicaxanthin transport was non-polarized and insensitive to the tested transporter inhibitors; EDTA treatment increased its passage. Model/species: Human Caco-2 epithelial monolayers on Transwell inserts Tissue: Apical/basolateral compartments Exposure: Dietary-consistent pigment concentrations, exact range not in accessed abstract; pH 6.0/7.4 gradient Route: In vitro transepithelial transport Duration: Time-course assay; exact interval not in accessed abstract Limits: Cell permeability is not a human absorption fraction. MRP2-mediated efflux in this paper concerns betanin, not indicaxanthin. Different protocols limit comparison with the 2022 transport paper. A paracellular contribution is supported; no specific transporter is assigned. Primary reference: Trans-epithelial transport of the betalain pigments indicaxanthin and betanin across Caco-2 cell monolayers and influence of food matrix. (2013). https://pubmed.ncbi.nlm.nih.gov/22806766/ DOI: 10.1007/s00394-012-0414-5 Access: Primary PubMed abstract.

dose

Dietary-consistent pigment concentrations, exact range not in accessed abstract; pH 6.0/7.4 gradient

duration

Time-course assay; exact interval not in accessed abstract

evidence_access

Primary PubMed abstract.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human Caco-2 epithelial monolayers on Transwell inserts

limitations

Cell permeability is not a human absorption fraction. MRP2-mediated efflux in this paper concerns betanin, not indicaxanthin. Different protocols limit comparison with the 2022 transport paper.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Human Caco-2 epithelial monolayers on Transwell inserts

plain_language

Indicaxanthin showed absorptive apparent permeability of 4.4 +/- 0.4 x 10^-6 cm/s in the 2013 Caco-2 transport experiment.

primary_references

Trans-epithelial transport of the betalain pigments indicaxanthin and betanin across Caco-2 cell monolayers and influence of food matrix. (2013). https://pubmed.ncbi.nlm.nih.gov/22806766/ DOI: 10.1007/s00394-012-0414-5

route

In vitro transepithelial transport

tissue

Apical/basolateral compartments

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 63–72

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Human Caco-2 epithelial monolayers on Transwell inserts · source_derived_draft · unverified_draft

## indicaxanthin-caco2-permeability Indicaxanthin showed absorptive apparent permeability of 4.4 +/- 0.4 x 10^-6 cm/s in the 2013 Caco-2 transport experiment. Model/species: Human Caco-2 epithelial monolayers on Transwell inserts Tissue: Apical/basolateral compartments Exposure: Dietary-consistent pigment concentrations, exact range not in accessed abstract; pH 6.0/7.4 gradient Route: In vitro transepithelial transport Duration: Time-course assay; exact interval not in accessed abstract Limits: Cell permeability is not a human absorption fraction. MRP2-mediated efflux in this paper concerns betanin, not indicaxanthin. Different protocols limit comparison with the 2022 transport paper. Primary reference: Trans-epithelial transport of the betalain pigments indicaxanthin and betanin across Caco-2 cell monolayers and influence of food matrix. (2013). https://pubmed.ncbi.nlm.nih.gov/22806766/ DOI: 10.1007/s00394-012-0414-5 Access: Primary PubMed abstract.

dose

Indicaxanthin 60 micromolar with cisplatin 10 micromolar; individual-agent controls

duration

24 h

evidence_access

Primary open full text, relevant results/methods and PubMed metadata.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human HeLa cervical cancer cells

limitations

Cell-culture chemosensitization is not clinical cancer efficacy. Redox-probe signals and protein changes do not prove direct target binding.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Human HeLa cervical cancer cells

plain_language

Co-treatment with indicaxanthin increased cisplatin-associated apoptosis in HeLa cells relative to cisplatin alone.

primary_references

The Phytochemical Indicaxanthin Synergistically Enhances Cisplatin-Induced Apoptosis in HeLa Cells via Oxidative Stress-Dependent p53/p21waf1 Axis. (2020). https://pubmed.ncbi.nlm.nih.gov/32630700/ DOI: 10.3390/biom10070994

route

In vitro co-treatment

tissue

Cell death and redox assays

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 283–292

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Human HeLa cervical cancer cells · source_derived_draft · unverified_draft

## indicaxanthin-cisplatin-apoptosis Co-treatment with indicaxanthin increased cisplatin-associated apoptosis in HeLa cells relative to cisplatin alone. Model/species: Human HeLa cervical cancer cells Tissue: Cell death and redox assays Exposure: Indicaxanthin 60 micromolar with cisplatin 10 micromolar; individual-agent controls Route: In vitro co-treatment Duration: 24 h Limits: Cell-culture chemosensitization is not clinical cancer efficacy. Redox-probe signals and protein changes do not prove direct target binding. Primary reference: The Phytochemical Indicaxanthin Synergistically Enhances Cisplatin-Induced Apoptosis in HeLa Cells via Oxidative Stress-Dependent p53/p21waf1 Axis. (2020). https://pubmed.ncbi.nlm.nih.gov/32630700/ DOI: 10.3390/biom10070994 Access: Primary open full text, relevant results/methods and PubMed metadata.

dose

Indicaxanthin 60 micromolar with cisplatin 10 micromolar; individual-agent controls

duration

24 h

evidence_access

Primary open full text, relevant results/methods and PubMed metadata.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human HeLa cervical cancer cells

limitations

Cell-culture chemosensitization is not clinical cancer efficacy. Redox-probe signals and protein changes do not prove direct target binding. Glutathione was assessed with CMFDA fluorescence; the result does not establish an isolated block of synthesis.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Human HeLa cervical cancer cells

plain_language

Indicaxanthin plus cisplatin lowered the glutathione-associated signal more than cisplatin alone in HeLa cells.

primary_references

The Phytochemical Indicaxanthin Synergistically Enhances Cisplatin-Induced Apoptosis in HeLa Cells via Oxidative Stress-Dependent p53/p21waf1 Axis. (2020). https://pubmed.ncbi.nlm.nih.gov/32630700/ DOI: 10.3390/biom10070994

route

In vitro co-treatment

tissue

Cell death and redox assays

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 294–303

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Human HeLa cervical cancer cells · source_derived_draft · unverified_draft

## indicaxanthin-cisplatin-gsh Indicaxanthin plus cisplatin lowered the glutathione-associated signal more than cisplatin alone in HeLa cells. Model/species: Human HeLa cervical cancer cells Tissue: Cell death and redox assays Exposure: Indicaxanthin 60 micromolar with cisplatin 10 micromolar; individual-agent controls Route: In vitro co-treatment Duration: 24 h Limits: Cell-culture chemosensitization is not clinical cancer efficacy. Redox-probe signals and protein changes do not prove direct target binding. Glutathione was assessed with CMFDA fluorescence; the result does not establish an isolated block of synthesis. Primary reference: The Phytochemical Indicaxanthin Synergistically Enhances Cisplatin-Induced Apoptosis in HeLa Cells via Oxidative Stress-Dependent p53/p21waf1 Axis. (2020). https://pubmed.ncbi.nlm.nih.gov/32630700/ DOI: 10.3390/biom10070994 Access: Primary open full text, relevant results/methods and PubMed metadata.

dose

Indicaxanthin 2, 5 or 10 micromolar plus a cisplatin concentration series

duration

24 h

evidence_access

Primary open full text, relevant results/methods and PubMed metadata.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human HeLa cervical cancer cells

limitations

Lower indicaxanthin concentrations were examined in a separate viability experiment; do not transfer all high-dose mechanistic measurements to this range.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Human HeLa cervical cancer cells

plain_language

Low-micromolar indicaxanthin enhanced the cisplatin-associated loss of HeLa-cell viability in a separate concentration-response experiment.

primary_references

The Phytochemical Indicaxanthin Synergistically Enhances Cisplatin-Induced Apoptosis in HeLa Cells via Oxidative Stress-Dependent p53/p21waf1 Axis. (2020). https://pubmed.ncbi.nlm.nih.gov/32630700/ DOI: 10.3390/biom10070994

route

In vitro co-treatment

tissue

Viability assay

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 316–325

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Human HeLa cervical cancer cells · source_derived_draft · unverified_draft

## indicaxanthin-cisplatin-low-dose Low-micromolar indicaxanthin enhanced the cisplatin-associated loss of HeLa-cell viability in a separate concentration-response experiment. Model/species: Human HeLa cervical cancer cells Tissue: Viability assay Exposure: Indicaxanthin 2, 5 or 10 micromolar plus a cisplatin concentration series Route: In vitro co-treatment Duration: 24 h Limits: Lower indicaxanthin concentrations were examined in a separate viability experiment; do not transfer all high-dose mechanistic measurements to this range. Primary reference: The Phytochemical Indicaxanthin Synergistically Enhances Cisplatin-Induced Apoptosis in HeLa Cells via Oxidative Stress-Dependent p53/p21waf1 Axis. (2020). https://pubmed.ncbi.nlm.nih.gov/32630700/ DOI: 10.3390/biom10070994 Access: Primary open full text, relevant results/methods and PubMed metadata.

dose

Indicaxanthin 60 micromolar with cisplatin 10 micromolar; individual-agent controls

duration

24 h

evidence_access

Primary open full text, relevant results/methods and PubMed metadata.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human HeLa cervical cancer cells

limitations

Cell-culture chemosensitization is not clinical cancer efficacy. Redox-probe signals and protein changes do not prove direct target binding.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Human HeLa cervical cancer cells

plain_language

Indicaxanthin plus cisplatin increased oxidant-sensitive fluorescence more than cisplatin alone in HeLa cells.

primary_references

The Phytochemical Indicaxanthin Synergistically Enhances Cisplatin-Induced Apoptosis in HeLa Cells via Oxidative Stress-Dependent p53/p21waf1 Axis. (2020). https://pubmed.ncbi.nlm.nih.gov/32630700/ DOI: 10.3390/biom10070994

route

In vitro co-treatment

tissue

Cell death and redox assays

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 305–314

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Human HeLa cervical cancer cells · source_derived_draft · unverified_draft

## indicaxanthin-cisplatin-ros Indicaxanthin plus cisplatin increased oxidant-sensitive fluorescence more than cisplatin alone in HeLa cells. Model/species: Human HeLa cervical cancer cells Tissue: Cell death and redox assays Exposure: Indicaxanthin 60 micromolar with cisplatin 10 micromolar; individual-agent controls Route: In vitro co-treatment Duration: 24 h Limits: Cell-culture chemosensitization is not clinical cancer efficacy. Redox-probe signals and protein changes do not prove direct target binding. Primary reference: The Phytochemical Indicaxanthin Synergistically Enhances Cisplatin-Induced Apoptosis in HeLa Cells via Oxidative Stress-Dependent p53/p21waf1 Axis. (2020). https://pubmed.ncbi.nlm.nih.gov/32630700/ DOI: 10.3390/biom10070994 Access: Primary open full text, relevant results/methods and PubMed metadata.

dose

Indicaxanthin 5-20 micromolar; human oxidized LDL 100 micrograms/mL

duration

1 h pretreatment followed by 16 h oxidized-LDL exposure

evidence_access

Primary open full text, relevant results/methods and PubMed metadata.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human umbilical vein endothelial cells / HUVECs

limitations

Expression rescue does not demonstrate plaque regression or ABCA1 cholesterol-efflux flux. Primary-source metadata check found no correction/retraction link; broader integrity not assessed.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Human umbilical vein endothelial cells / HUVECs

plain_language

Indicaxanthin pretreatment prevented the oxidized-LDL-associated decrease in ABCA1 mRNA and protein in HUVECs.

primary_references

Indicaxanthin from Opuntia ficus indica (L. Mill) Inhibits Oxidized LDL-Mediated Human Endothelial Cell Dysfunction through Inhibition of NF-κB Activation. (2019). https://pubmed.ncbi.nlm.nih.gov/30911345/ DOI: 10.1155/2019/3457846

route

In vitro pretreatment and challenge

tissue

Endothelial culture

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 349–358

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Human umbilical vein endothelial cells / HUVECs · source_derived_draft · unverified_draft

## indicaxanthin-endothelial-abca1 Indicaxanthin pretreatment prevented the oxidized-LDL-associated decrease in ABCA1 mRNA and protein in HUVECs. Model/species: Human umbilical vein endothelial cells / HUVECs Tissue: Endothelial culture Exposure: Indicaxanthin 5-20 micromolar; human oxidized LDL 100 micrograms/mL Route: In vitro pretreatment and challenge Duration: 1 h pretreatment followed by 16 h oxidized-LDL exposure Limits: Expression rescue does not demonstrate plaque regression or ABCA1 cholesterol-efflux flux. Primary-source metadata check found no correction/retraction link; broader integrity not assessed. Primary reference: Indicaxanthin from Opuntia ficus indica (L. Mill) Inhibits Oxidized LDL-Mediated Human Endothelial Cell Dysfunction through Inhibition of NF-κB Activation. (2019). https://pubmed.ncbi.nlm.nih.gov/30911345/ DOI: 10.1155/2019/3457846 Access: Primary open full text, relevant results/methods and PubMed metadata.

dose

Indicaxanthin 5-20 micromolar; human oxidized LDL 100 micrograms/mL

duration

1 h pretreatment followed by 16 h oxidized-LDL exposure

evidence_access

Primary open full text, relevant results/methods and PubMed metadata.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human umbilical vein endothelial cells / HUVECs

limitations

Expression rescue does not demonstrate plaque regression or ABCA1 cholesterol-efflux flux. Primary-source metadata check found no correction/retraction link; broader integrity not assessed.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Human umbilical vein endothelial cells / HUVECs

plain_language

Indicaxanthin pretreatment reduced oxidized-LDL-induced ICAM1 mRNA and protein increases in HUVECs.

primary_references

Indicaxanthin from Opuntia ficus indica (L. Mill) Inhibits Oxidized LDL-Mediated Human Endothelial Cell Dysfunction through Inhibition of NF-κB Activation. (2019). https://pubmed.ncbi.nlm.nih.gov/30911345/ DOI: 10.1155/2019/3457846

route

In vitro pretreatment and challenge

tissue

Endothelial culture

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 360–369

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Human umbilical vein endothelial cells / HUVECs · source_derived_draft · unverified_draft

## indicaxanthin-endothelial-icam1 Indicaxanthin pretreatment reduced oxidized-LDL-induced ICAM1 mRNA and protein increases in HUVECs. Model/species: Human umbilical vein endothelial cells / HUVECs Tissue: Endothelial culture Exposure: Indicaxanthin 5-20 micromolar; human oxidized LDL 100 micrograms/mL Route: In vitro pretreatment and challenge Duration: 1 h pretreatment followed by 16 h oxidized-LDL exposure Limits: Expression rescue does not demonstrate plaque regression or ABCA1 cholesterol-efflux flux. Primary-source metadata check found no correction/retraction link; broader integrity not assessed. Primary reference: Indicaxanthin from Opuntia ficus indica (L. Mill) Inhibits Oxidized LDL-Mediated Human Endothelial Cell Dysfunction through Inhibition of NF-κB Activation. (2019). https://pubmed.ncbi.nlm.nih.gov/30911345/ DOI: 10.1155/2019/3457846 Access: Primary open full text, relevant results/methods and PubMed metadata.

dose

Indicaxanthin 5-20 micromolar; human oxidized LDL 100 micrograms/mL

duration

1 h pretreatment followed by 16 h oxidized-LDL exposure

evidence_access

Primary open full text, relevant results/methods and PubMed metadata.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human umbilical vein endothelial cells / HUVECs

limitations

Expression rescue does not demonstrate plaque regression or ABCA1 cholesterol-efflux flux. Primary-source metadata check found no correction/retraction link; broader integrity not assessed.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Human umbilical vein endothelial cells / HUVECs

plain_language

Indicaxanthin pretreatment suppressed oxidized-LDL-induced NF-kappaB transcriptional activity in HUVECs.

primary_references

Indicaxanthin from Opuntia ficus indica (L. Mill) Inhibits Oxidized LDL-Mediated Human Endothelial Cell Dysfunction through Inhibition of NF-κB Activation. (2019). https://pubmed.ncbi.nlm.nih.gov/30911345/ DOI: 10.1155/2019/3457846

route

In vitro pretreatment and challenge

tissue

Endothelial culture

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 338–347

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Human umbilical vein endothelial cells / HUVECs · source_derived_draft · unverified_draft

## indicaxanthin-endothelial-nfkb Indicaxanthin pretreatment suppressed oxidized-LDL-induced NF-kappaB transcriptional activity in HUVECs. Model/species: Human umbilical vein endothelial cells / HUVECs Tissue: Endothelial culture Exposure: Indicaxanthin 5-20 micromolar; human oxidized LDL 100 micrograms/mL Route: In vitro pretreatment and challenge Duration: 1 h pretreatment followed by 16 h oxidized-LDL exposure Limits: Expression rescue does not demonstrate plaque regression or ABCA1 cholesterol-efflux flux. Primary-source metadata check found no correction/retraction link; broader integrity not assessed. Primary reference: Indicaxanthin from Opuntia ficus indica (L. Mill) Inhibits Oxidized LDL-Mediated Human Endothelial Cell Dysfunction through Inhibition of NF-κB Activation. (2019). https://pubmed.ncbi.nlm.nih.gov/30911345/ DOI: 10.1155/2019/3457846 Access: Primary open full text, relevant results/methods and PubMed metadata.

dose

Indicaxanthin 5-20 micromolar; human oxidized LDL 100 micrograms/mL

duration

1 h pretreatment followed by 16 h oxidized-LDL exposure

evidence_access

Primary open full text, relevant results/methods and PubMed metadata.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human umbilical vein endothelial cells / HUVECs

limitations

Expression rescue does not demonstrate plaque regression or ABCA1 cholesterol-efflux flux. Primary-source metadata check found no correction/retraction link; broader integrity not assessed.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Human umbilical vein endothelial cells / HUVECs

plain_language

Indicaxanthin pretreatment reduced oxidized-LDL-induced VCAM1 mRNA and protein increases in HUVECs.

primary_references

Indicaxanthin from Opuntia ficus indica (L. Mill) Inhibits Oxidized LDL-Mediated Human Endothelial Cell Dysfunction through Inhibition of NF-κB Activation. (2019). https://pubmed.ncbi.nlm.nih.gov/30911345/ DOI: 10.1155/2019/3457846

route

In vitro pretreatment and challenge

tissue

Endothelial culture

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 371–380

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Human umbilical vein endothelial cells / HUVECs · source_derived_draft · unverified_draft

## indicaxanthin-endothelial-vcam1 Indicaxanthin pretreatment reduced oxidized-LDL-induced VCAM1 mRNA and protein increases in HUVECs. Model/species: Human umbilical vein endothelial cells / HUVECs Tissue: Endothelial culture Exposure: Indicaxanthin 5-20 micromolar; human oxidized LDL 100 micrograms/mL Route: In vitro pretreatment and challenge Duration: 1 h pretreatment followed by 16 h oxidized-LDL exposure Limits: Expression rescue does not demonstrate plaque regression or ABCA1 cholesterol-efflux flux. Primary-source metadata check found no correction/retraction link; broader integrity not assessed. Primary reference: Indicaxanthin from Opuntia ficus indica (L. Mill) Inhibits Oxidized LDL-Mediated Human Endothelial Cell Dysfunction through Inhibition of NF-κB Activation. (2019). https://pubmed.ncbi.nlm.nih.gov/30911345/ DOI: 10.1155/2019/3457846 Access: Primary open full text, relevant results/methods and PubMed metadata.

dose

Indicaxanthin 10, 50 and 100 micromolar

duration

48 h

evidence_access

Primary open full text, relevant results/methods and PubMed metadata.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human Caco-2 colorectal cancer cells

limitations

Marker abundance and acidic organelles are not sufficient alone to quantify complete autophagic flux. Predicted BCL2 binding remains computational; methylation associations do not prove causation.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Human Caco-2 colorectal cancer cells

plain_language

Indicaxanthin treatment shifted the Caco-2 RRBS profile toward greater genomic CpG methylation, most strongly at 50 micromolar.

primary_references

Indicaxanthin Induces Autophagy in Intestinal Epithelial Cancer Cells by Epigenetic Mechanisms Involving DNA Methylation. (2023). https://pubmed.ncbi.nlm.nih.gov/37571432/ DOI: 10.3390/nu15153495

route

In vitro addition

tissue

Autophagy markers and DNA methylome

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 448–457

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Human Caco-2 colorectal cancer cells · source_derived_draft · unverified_draft

## indicaxanthin-global-methylation Indicaxanthin treatment shifted the Caco-2 RRBS profile toward greater genomic CpG methylation, most strongly at 50 micromolar. Model/species: Human Caco-2 colorectal cancer cells Tissue: Autophagy markers and DNA methylome Exposure: Indicaxanthin 10, 50 and 100 micromolar Route: In vitro addition Duration: 48 h Limits: Marker abundance and acidic organelles are not sufficient alone to quantify complete autophagic flux. Predicted BCL2 binding remains computational; methylation associations do not prove causation. Primary reference: Indicaxanthin Induces Autophagy in Intestinal Epithelial Cancer Cells by Epigenetic Mechanisms Involving DNA Methylation. (2023). https://pubmed.ncbi.nlm.nih.gov/37571432/ DOI: 10.3390/nu15153495 Access: Primary open full text, relevant results/methods and PubMed metadata.

dose

High-fat diet for 10 weeks then indicaxanthin for 4 weeks; abstract reports 0.86 mg/kg/day, methods state 0.4 mg/kg twice daily

duration

4 treatment weeks; eight mice/group

evidence_access

Primary open full text, relevant results/methods and PubMed metadata.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Male mice with diet-induced obesity

limitations

Dose wording differs between abstract and methods and is preserved unresolved. Changes in microbial abundance do not demonstrate measured SCFA production or microbiota-mediated causation of brain changes. Article assigned 2026 issue; earlier online indexing retained in PubMed.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Male mice with diet-induced obesity

plain_language

Oral indicaxanthin reduced cortical TUNEL-positive cells in high-fat-diet-fed male mice.

primary_references

Positive impact of indicaxanthin from Opuntia ficus-indica fruit on high-fat diet-induced neuronal damage and gut microbiota dysbiosis. (2026). https://pubmed.ncbi.nlm.nih.gov/39314163/ DOI: 10.4103/NRR.NRR-D-23-02039

route

Oral indicaxanthin in water

tissue

Cerebral cortex and gut microbiota

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 470–479

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Male mice with diet-induced obesity · source_derived_draft · unverified_draft

## indicaxanthin-hfd-cortical-cell-death Oral indicaxanthin reduced cortical TUNEL-positive cells in high-fat-diet-fed male mice. Model/species: Male mice with diet-induced obesity Tissue: Cerebral cortex and gut microbiota Exposure: High-fat diet for 10 weeks then indicaxanthin for 4 weeks; abstract reports 0.86 mg/kg/day, methods state 0.4 mg/kg twice daily Route: Oral indicaxanthin in water Duration: 4 treatment weeks; eight mice/group Limits: Dose wording differs between abstract and methods and is preserved unresolved. Changes in microbial abundance do not demonstrate measured SCFA production or microbiota-mediated causation of brain changes. Article assigned 2026 issue; earlier online indexing retained in PubMed. Primary reference: Positive impact of indicaxanthin from Opuntia ficus-indica fruit on high-fat diet-induced neuronal damage and gut microbiota dysbiosis. (2026). https://pubmed.ncbi.nlm.nih.gov/39314163/ DOI: 10.4103/NRR.NRR-D-23-02039 Access: Primary open full text, relevant results/methods and PubMed metadata.

dose

High-fat diet for 10 weeks then indicaxanthin for 4 weeks; abstract reports 0.86 mg/kg/day, methods state 0.4 mg/kg twice daily

duration

4 treatment weeks; eight mice/group

evidence_access

Primary open full text, relevant results/methods and PubMed metadata.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Male mice with diet-induced obesity

limitations

Dose wording differs between abstract and methods and is preserved unresolved. Changes in microbial abundance do not demonstrate measured SCFA production or microbiota-mediated causation of brain changes. Article assigned 2026 issue; earlier online indexing retained in PubMed.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Male mice with diet-induced obesity

plain_language

Oral indicaxanthin altered gut microbial relative abundances in high-fat-diet-fed male mice.

primary_references

Positive impact of indicaxanthin from Opuntia ficus-indica fruit on high-fat diet-induced neuronal damage and gut microbiota dysbiosis. (2026). https://pubmed.ncbi.nlm.nih.gov/39314163/ DOI: 10.4103/NRR.NRR-D-23-02039

route

Oral indicaxanthin in water

tissue

Cerebral cortex and gut microbiota

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 481–490

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Male mice with diet-induced obesity · source_derived_draft · unverified_draft

## indicaxanthin-hfd-microbiota Oral indicaxanthin altered gut microbial relative abundances in high-fat-diet-fed male mice. Model/species: Male mice with diet-induced obesity Tissue: Cerebral cortex and gut microbiota Exposure: High-fat diet for 10 weeks then indicaxanthin for 4 weeks; abstract reports 0.86 mg/kg/day, methods state 0.4 mg/kg twice daily Route: Oral indicaxanthin in water Duration: 4 treatment weeks; eight mice/group Limits: Dose wording differs between abstract and methods and is preserved unresolved. Changes in microbial abundance do not demonstrate measured SCFA production or microbiota-mediated causation of brain changes. Article assigned 2026 issue; earlier online indexing retained in PubMed. Primary reference: Positive impact of indicaxanthin from Opuntia ficus-indica fruit on high-fat diet-induced neuronal damage and gut microbiota dysbiosis. (2026). https://pubmed.ncbi.nlm.nih.gov/39314163/ DOI: 10.4103/NRR.NRR-D-23-02039 Access: Primary open full text, relevant results/methods and PubMed metadata.

dose

Indicaxanthin; forskolin, IBMX and other pharmacological probes, exact concentrations not in accessed abstract

duration

Acute responses; exact interval not in accessed abstract

evidence_access

Primary PubMed abstract.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Isolated mouse ileal longitudinal muscle

limitations

PDE involvement is inferred pharmacologically, not established by an isoform-specific binding or purified-enzyme assay; no clinical motility treatment is tested.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Isolated mouse ileal longitudinal muscle

plain_language

Adding indicaxanthin increased basal and forskolin-stimulated cAMP in mouse ileal muscle.

primary_references

Inhibitory effects of indicaxanthin on mouse ileal contractility: analysis of the mechanism of action. (2011). https://pubmed.ncbi.nlm.nih.gov/21371457/ DOI: 10.1016/j.ejphar.2011.02.034

route

Ex vivo organ-bath addition

tissue

Organ-bath smooth muscle

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 96–105

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Isolated mouse ileal longitudinal muscle · source_derived_draft · unverified_draft

## indicaxanthin-ileal-camp Adding indicaxanthin increased basal and forskolin-stimulated cAMP in mouse ileal muscle. Model/species: Isolated mouse ileal longitudinal muscle Tissue: Organ-bath smooth muscle Exposure: Indicaxanthin; forskolin, IBMX and other pharmacological probes, exact concentrations not in accessed abstract Route: Ex vivo organ-bath addition Duration: Acute responses; exact interval not in accessed abstract Limits: PDE involvement is inferred pharmacologically, not established by an isoform-specific binding or purified-enzyme assay; no clinical motility treatment is tested. Primary reference: Inhibitory effects of indicaxanthin on mouse ileal contractility: analysis of the mechanism of action. (2011). https://pubmed.ncbi.nlm.nih.gov/21371457/ DOI: 10.1016/j.ejphar.2011.02.034 Access: Primary PubMed abstract.

dose

Indicaxanthin; forskolin, IBMX and other pharmacological probes, exact concentrations not in accessed abstract

duration

Acute responses; exact interval not in accessed abstract

evidence_access

Primary PubMed abstract.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Isolated mouse ileal longitudinal muscle

limitations

PDE involvement is inferred pharmacologically, not established by an isoform-specific binding or purified-enzyme assay; no clinical motility treatment is tested.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Isolated mouse ileal longitudinal muscle

plain_language

Adding indicaxanthin reduced spontaneous contractile activity of isolated mouse ileal longitudinal muscle.

primary_references

Inhibitory effects of indicaxanthin on mouse ileal contractility: analysis of the mechanism of action. (2011). https://pubmed.ncbi.nlm.nih.gov/21371457/ DOI: 10.1016/j.ejphar.2011.02.034

route

Ex vivo organ-bath addition

tissue

Organ-bath smooth muscle

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

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Isolated mouse ileal longitudinal muscle · source_derived_draft · unverified_draft

## indicaxanthin-ileal-contractility Adding indicaxanthin reduced spontaneous contractile activity of isolated mouse ileal longitudinal muscle. Model/species: Isolated mouse ileal longitudinal muscle Tissue: Organ-bath smooth muscle Exposure: Indicaxanthin; forskolin, IBMX and other pharmacological probes, exact concentrations not in accessed abstract Route: Ex vivo organ-bath addition Duration: Acute responses; exact interval not in accessed abstract Limits: PDE involvement is inferred pharmacologically, not established by an isoform-specific binding or purified-enzyme assay; no clinical motility treatment is tested. Primary reference: Inhibitory effects of indicaxanthin on mouse ileal contractility: analysis of the mechanism of action. (2011). https://pubmed.ncbi.nlm.nih.gov/21371457/ DOI: 10.1016/j.ejphar.2011.02.034 Access: Primary PubMed abstract.

dose

Indicaxanthin; forskolin, IBMX and other pharmacological probes, exact concentrations not in accessed abstract

duration

Acute responses; exact interval not in accessed abstract

evidence_access

Primary PubMed abstract.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Isolated mouse ileal longitudinal muscle

limitations

PDE involvement is inferred pharmacologically, not established by an isoform-specific binding or purified-enzyme assay; no clinical motility treatment is tested.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Isolated mouse ileal longitudinal muscle

plain_language

Indicaxanthin enhanced the inhibitory effect of forskolin on mouse ileal mechanical activity.

primary_references

Inhibitory effects of indicaxanthin on mouse ileal contractility: analysis of the mechanism of action. (2011). https://pubmed.ncbi.nlm.nih.gov/21371457/ DOI: 10.1016/j.ejphar.2011.02.034

route

Ex vivo organ-bath addition

tissue

Organ-bath smooth muscle

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 107–116

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Isolated mouse ileal longitudinal muscle · source_derived_draft · unverified_draft

## indicaxanthin-ileal-forskolin Indicaxanthin enhanced the inhibitory effect of forskolin on mouse ileal mechanical activity. Model/species: Isolated mouse ileal longitudinal muscle Tissue: Organ-bath smooth muscle Exposure: Indicaxanthin; forskolin, IBMX and other pharmacological probes, exact concentrations not in accessed abstract Route: Ex vivo organ-bath addition Duration: Acute responses; exact interval not in accessed abstract Limits: PDE involvement is inferred pharmacologically, not established by an isoform-specific binding or purified-enzyme assay; no clinical motility treatment is tested. Primary reference: Inhibitory effects of indicaxanthin on mouse ileal contractility: analysis of the mechanism of action. (2011). https://pubmed.ncbi.nlm.nih.gov/21371457/ DOI: 10.1016/j.ejphar.2011.02.034 Access: Primary PubMed abstract.

dose

Indicaxanthin 50-100 micromolar; LPS 1 microgram/mL

duration

Indicaxanthin 1 h before LPS; signaling time courses 0.5-16 h

evidence_access

Primary open full text, relevant results/methods and PubMed metadata.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Mouse RAW 264.7 macrophages

limitations

High cell-culture exposure; expression changes are not direct enzyme binding. Pro-oxidant signaling in this setting differs from red-cell antioxidant preservation. Opposite to the COX-2 response in IL-1beta-exposed human intestinal cells; different species, stimulus and concentration are retained rather than declared a contradiction.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Mouse RAW 264.7 macrophages

plain_language

Indicaxanthin pretreatment increased COX-2 expression in LPS-stimulated RAW 264.7 cells.

primary_references

Pro-oxidant activity of indicaxanthin from Opuntia ficus indica modulates arachidonate metabolism and prostaglandin synthesis through lipid peroxide production in LPS-stimulated RAW 264.7 macrophages. (2014). https://pubmed.ncbi.nlm.nih.gov/25180166/ DOI: 10.1016/j.redox.2014.07.004

route

In vitro pretreatment then challenge

tissue

Cellular membranes and prostaglandin pathway

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 129–138

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Mouse RAW 264.7 macrophages · source_derived_draft · unverified_draft

## indicaxanthin-macrophage-cox2 Indicaxanthin pretreatment increased COX-2 expression in LPS-stimulated RAW 264.7 cells. Model/species: Mouse RAW 264.7 macrophages Tissue: Cellular membranes and prostaglandin pathway Exposure: Indicaxanthin 50-100 micromolar; LPS 1 microgram/mL Route: In vitro pretreatment then challenge Duration: Indicaxanthin 1 h before LPS; signaling time courses 0.5-16 h Limits: High cell-culture exposure; expression changes are not direct enzyme binding. Pro-oxidant signaling in this setting differs from red-cell antioxidant preservation. Opposite to the COX-2 response in IL-1beta-exposed human intestinal cells; different species, stimulus and concentration are retained rather than declared a contradiction. Primary reference: Pro-oxidant activity of indicaxanthin from Opuntia ficus indica modulates arachidonate metabolism and prostaglandin synthesis through lipid peroxide production in LPS-stimulated RAW 264.7 macrophages. (2014). https://pubmed.ncbi.nlm.nih.gov/25180166/ DOI: 10.1016/j.redox.2014.07.004 Access: Primary open full text, relevant results/methods and PubMed metadata.

dose

Indicaxanthin 50-100 micromolar; LPS 1 microgram/mL

duration

Indicaxanthin 1 h before LPS; signaling time courses 0.5-16 h

evidence_access

Primary open full text, relevant results/methods and PubMed metadata.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Mouse RAW 264.7 macrophages

limitations

High cell-culture exposure; expression changes are not direct enzyme binding. Pro-oxidant signaling in this setting differs from red-cell antioxidant preservation.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Mouse RAW 264.7 macrophages

plain_language

Indicaxanthin pretreatment increased hematopoietic PGD synthase expression in LPS-stimulated RAW 264.7 cells.

primary_references

Pro-oxidant activity of indicaxanthin from Opuntia ficus indica modulates arachidonate metabolism and prostaglandin synthesis through lipid peroxide production in LPS-stimulated RAW 264.7 macrophages. (2014). https://pubmed.ncbi.nlm.nih.gov/25180166/ DOI: 10.1016/j.redox.2014.07.004

route

In vitro pretreatment then challenge

tissue

Cellular membranes and prostaglandin pathway

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 140–149

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Mouse RAW 264.7 macrophages · source_derived_draft · unverified_draft

## indicaxanthin-macrophage-hpgds Indicaxanthin pretreatment increased hematopoietic PGD synthase expression in LPS-stimulated RAW 264.7 cells. Model/species: Mouse RAW 264.7 macrophages Tissue: Cellular membranes and prostaglandin pathway Exposure: Indicaxanthin 50-100 micromolar; LPS 1 microgram/mL Route: In vitro pretreatment then challenge Duration: Indicaxanthin 1 h before LPS; signaling time courses 0.5-16 h Limits: High cell-culture exposure; expression changes are not direct enzyme binding. Pro-oxidant signaling in this setting differs from red-cell antioxidant preservation. Primary reference: Pro-oxidant activity of indicaxanthin from Opuntia ficus indica modulates arachidonate metabolism and prostaglandin synthesis through lipid peroxide production in LPS-stimulated RAW 264.7 macrophages. (2014). https://pubmed.ncbi.nlm.nih.gov/25180166/ DOI: 10.1016/j.redox.2014.07.004 Access: Primary open full text, relevant results/methods and PubMed metadata.

dose

Indicaxanthin 50-100 micromolar; LPS 1 microgram/mL

duration

Indicaxanthin 1 h before LPS; signaling time courses 0.5-16 h

evidence_access

Primary open full text, relevant results/methods and PubMed metadata.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Mouse RAW 264.7 macrophages

limitations

High cell-culture exposure; expression changes are not direct enzyme binding. Pro-oxidant signaling in this setting differs from red-cell antioxidant preservation.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Mouse RAW 264.7 macrophages

plain_language

Indicaxanthin increased early lipid hydroperoxide accumulation above the LPS-only level in RAW 264.7 cells.

primary_references

Pro-oxidant activity of indicaxanthin from Opuntia ficus indica modulates arachidonate metabolism and prostaglandin synthesis through lipid peroxide production in LPS-stimulated RAW 264.7 macrophages. (2014). https://pubmed.ncbi.nlm.nih.gov/25180166/ DOI: 10.1016/j.redox.2014.07.004

route

In vitro pretreatment then challenge

tissue

Cellular membranes and prostaglandin pathway

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 162–171

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Mouse RAW 264.7 macrophages · source_derived_draft · unverified_draft

## indicaxanthin-macrophage-lipid-peroxides Indicaxanthin increased early lipid hydroperoxide accumulation above the LPS-only level in RAW 264.7 cells. Model/species: Mouse RAW 264.7 macrophages Tissue: Cellular membranes and prostaglandin pathway Exposure: Indicaxanthin 50-100 micromolar; LPS 1 microgram/mL Route: In vitro pretreatment then challenge Duration: Indicaxanthin 1 h before LPS; signaling time courses 0.5-16 h Limits: High cell-culture exposure; expression changes are not direct enzyme binding. Pro-oxidant signaling in this setting differs from red-cell antioxidant preservation. Primary reference: Pro-oxidant activity of indicaxanthin from Opuntia ficus indica modulates arachidonate metabolism and prostaglandin synthesis through lipid peroxide production in LPS-stimulated RAW 264.7 macrophages. (2014). https://pubmed.ncbi.nlm.nih.gov/25180166/ DOI: 10.1016/j.redox.2014.07.004 Access: Primary open full text, relevant results/methods and PubMed metadata.

dose

Indicaxanthin 50-100 micromolar; LPS 1 microgram/mL

duration

Indicaxanthin 1 h before LPS; signaling time courses 0.5-16 h

evidence_access

Primary open full text, relevant results/methods and PubMed metadata.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Mouse RAW 264.7 macrophages

limitations

High cell-culture exposure; expression changes are not direct enzyme binding. Pro-oxidant signaling in this setting differs from red-cell antioxidant preservation.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Mouse RAW 264.7 macrophages

plain_language

Indicaxanthin pretreatment reduced LPS-induced microsomal PGE synthase-1 overexpression in RAW 264.7 cells.

primary_references

Pro-oxidant activity of indicaxanthin from Opuntia ficus indica modulates arachidonate metabolism and prostaglandin synthesis through lipid peroxide production in LPS-stimulated RAW 264.7 macrophages. (2014). https://pubmed.ncbi.nlm.nih.gov/25180166/ DOI: 10.1016/j.redox.2014.07.004

route

In vitro pretreatment then challenge

tissue

Cellular membranes and prostaglandin pathway

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

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Mouse RAW 264.7 macrophages · source_derived_draft · unverified_draft

## indicaxanthin-macrophage-mpges Indicaxanthin pretreatment reduced LPS-induced microsomal PGE synthase-1 overexpression in RAW 264.7 cells. Model/species: Mouse RAW 264.7 macrophages Tissue: Cellular membranes and prostaglandin pathway Exposure: Indicaxanthin 50-100 micromolar; LPS 1 microgram/mL Route: In vitro pretreatment then challenge Duration: Indicaxanthin 1 h before LPS; signaling time courses 0.5-16 h Limits: High cell-culture exposure; expression changes are not direct enzyme binding. Pro-oxidant signaling in this setting differs from red-cell antioxidant preservation. Primary reference: Pro-oxidant activity of indicaxanthin from Opuntia ficus indica modulates arachidonate metabolism and prostaglandin synthesis through lipid peroxide production in LPS-stimulated RAW 264.7 macrophages. (2014). https://pubmed.ncbi.nlm.nih.gov/25180166/ DOI: 10.1016/j.redox.2014.07.004 Access: Primary open full text, relevant results/methods and PubMed metadata.

dose

Indicaxanthin 50-100 micromolar; LPS 1 microgram/mL

duration

Indicaxanthin 1 h before LPS; signaling time courses 0.5-16 h

evidence_access

Primary open full text, relevant results/methods and PubMed metadata.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Mouse RAW 264.7 macrophages

limitations

High cell-culture exposure; expression changes are not direct enzyme binding. Pro-oxidant signaling in this setting differs from red-cell antioxidant preservation.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Mouse RAW 264.7 macrophages

plain_language

Indicaxanthin pretreatment increased production of 15-deoxy-PGJ2 in LPS-stimulated RAW 264.7 cells.

primary_references

Pro-oxidant activity of indicaxanthin from Opuntia ficus indica modulates arachidonate metabolism and prostaglandin synthesis through lipid peroxide production in LPS-stimulated RAW 264.7 macrophages. (2014). https://pubmed.ncbi.nlm.nih.gov/25180166/ DOI: 10.1016/j.redox.2014.07.004

route

In vitro pretreatment then challenge

tissue

Cellular membranes and prostaglandin pathway

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 151–160

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Mouse RAW 264.7 macrophages · source_derived_draft · unverified_draft

## indicaxanthin-macrophage-pgj2 Indicaxanthin pretreatment increased production of 15-deoxy-PGJ2 in LPS-stimulated RAW 264.7 cells. Model/species: Mouse RAW 264.7 macrophages Tissue: Cellular membranes and prostaglandin pathway Exposure: Indicaxanthin 50-100 micromolar; LPS 1 microgram/mL Route: In vitro pretreatment then challenge Duration: Indicaxanthin 1 h before LPS; signaling time courses 0.5-16 h Limits: High cell-culture exposure; expression changes are not direct enzyme binding. Pro-oxidant signaling in this setting differs from red-cell antioxidant preservation. Primary reference: Pro-oxidant activity of indicaxanthin from Opuntia ficus indica modulates arachidonate metabolism and prostaglandin synthesis through lipid peroxide production in LPS-stimulated RAW 264.7 macrophages. (2014). https://pubmed.ncbi.nlm.nih.gov/25180166/ DOI: 10.1016/j.redox.2014.07.004 Access: Primary open full text, relevant results/methods and PubMed metadata.

dose

Purified indicaxanthin; growth IC50 115 +/- 15 micromolar, exact exposure series not in accessed abstract

duration

Exposure duration not specified in the accessed primary abstract

evidence_access

Primary PubMed abstract.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Proliferating human Caco-2 colorectal cancer cells

limitations

Locus-specific demethylation does not imply universal DNA demethylation. A cell-line response is not cancer prevention in people.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Proliferating human Caco-2 colorectal cancer cells

plain_language

Indicaxanthin treatment reactivated p16INK4a mRNA and increased its protein in Caco-2 cells.

primary_references

Anti-proliferative and pro-apoptotic activity of whole extract and isolated indicaxanthin from Opuntia ficus-indica associated with re-activation of the onco-suppressor p16(INK4a) gene in human colorectal carcinoma (Caco-2) cells. (2014). https://pubmed.ncbi.nlm.nih.gov/24937448/ DOI: 10.1016/j.bbrc.2014.06.029

route

In vitro addition

tissue

Epigenetic and growth assays

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 393–402

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Proliferating human Caco-2 colorectal cancer cells · source_derived_draft · unverified_draft

## indicaxanthin-p16-expression Indicaxanthin treatment reactivated p16INK4a mRNA and increased its protein in Caco-2 cells. Model/species: Proliferating human Caco-2 colorectal cancer cells Tissue: Epigenetic and growth assays Exposure: Purified indicaxanthin; growth IC50 115 +/- 15 micromolar, exact exposure series not in accessed abstract Route: In vitro addition Duration: Exposure duration not specified in the accessed primary abstract Limits: Locus-specific demethylation does not imply universal DNA demethylation. A cell-line response is not cancer prevention in people. Primary reference: Anti-proliferative and pro-apoptotic activity of whole extract and isolated indicaxanthin from Opuntia ficus-indica associated with re-activation of the onco-suppressor p16(INK4a) gene in human colorectal carcinoma (Caco-2) cells. (2014). https://pubmed.ncbi.nlm.nih.gov/24937448/ DOI: 10.1016/j.bbrc.2014.06.029 Access: Primary PubMed abstract.

dose

Purified indicaxanthin; growth IC50 115 +/- 15 micromolar, exact exposure series not in accessed abstract

duration

Exposure duration not specified in the accessed primary abstract

evidence_access

Primary PubMed abstract.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Proliferating human Caco-2 colorectal cancer cells

limitations

Locus-specific demethylation does not imply universal DNA demethylation. A cell-line response is not cancer prevention in people.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Proliferating human Caco-2 colorectal cancer cells

plain_language

Indicaxanthin treatment demethylated the p16INK4a promoter in proliferating Caco-2 cells.

primary_references

Anti-proliferative and pro-apoptotic activity of whole extract and isolated indicaxanthin from Opuntia ficus-indica associated with re-activation of the onco-suppressor p16(INK4a) gene in human colorectal carcinoma (Caco-2) cells. (2014). https://pubmed.ncbi.nlm.nih.gov/24937448/ DOI: 10.1016/j.bbrc.2014.06.029

route

In vitro addition

tissue

Epigenetic and growth assays

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 382–391

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Proliferating human Caco-2 colorectal cancer cells · source_derived_draft · unverified_draft

## indicaxanthin-p16-promoter Indicaxanthin treatment demethylated the p16INK4a promoter in proliferating Caco-2 cells. Model/species: Proliferating human Caco-2 colorectal cancer cells Tissue: Epigenetic and growth assays Exposure: Purified indicaxanthin; growth IC50 115 +/- 15 micromolar, exact exposure series not in accessed abstract Route: In vitro addition Duration: Exposure duration not specified in the accessed primary abstract Limits: Locus-specific demethylation does not imply universal DNA demethylation. A cell-line response is not cancer prevention in people. Primary reference: Anti-proliferative and pro-apoptotic activity of whole extract and isolated indicaxanthin from Opuntia ficus-indica associated with re-activation of the onco-suppressor p16(INK4a) gene in human colorectal carcinoma (Caco-2) cells. (2014). https://pubmed.ncbi.nlm.nih.gov/24937448/ DOI: 10.1016/j.bbrc.2014.06.029 Access: Primary PubMed abstract.

dose

Indicaxanthin compared with Trolox and vitamin C; exact concentrations not in accessed abstract

duration

Spectrophotometric kinetic assay

evidence_access

Primary PubMed abstract.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Cell-free haemoglobin redox preparation

limitations

A haemoglobin intermediate was reduced; dietary iron chelation and human treatment efficacy were not established.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Cell-free haemoglobin redox preparation

plain_language

Indicaxanthin reduced the perferryl-haemoglobin intermediate in the spectrophotometric reaction system.

primary_references

Cytoprotective effects of the antioxidant phytochemical indicaxanthin in beta-thalassemia red blood cells. (2006). https://pubmed.ncbi.nlm.nih.gov/16984002/ DOI: 10.1080/10715760600554228

route

In vitro addition

tissue

Met-Hb/peroxide reaction mixture

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

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Cell-free haemoglobin redox preparation · source_derived_draft · unverified_draft

## indicaxanthin-perferryl-hb Indicaxanthin reduced the perferryl-haemoglobin intermediate in the spectrophotometric reaction system. Model/species: Cell-free haemoglobin redox preparation Tissue: Met-Hb/peroxide reaction mixture Exposure: Indicaxanthin compared with Trolox and vitamin C; exact concentrations not in accessed abstract Route: In vitro addition Duration: Spectrophotometric kinetic assay Limits: A haemoglobin intermediate was reduced; dietary iron chelation and human treatment efficacy were not established. Primary reference: Cytoprotective effects of the antioxidant phytochemical indicaxanthin in beta-thalassemia red blood cells. (2006). https://pubmed.ncbi.nlm.nih.gov/16984002/ DOI: 10.1080/10715760600554228 Access: Primary PubMed abstract.

dose

Indicaxanthin 2 micromol/kg

duration

Detected within 1 h, peak at 2.5 h, disappearance by approximately 4 h

evidence_access

Primary PubMed abstract.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Rats given purified indicaxanthin

limitations

Brain exposure in rats does not demonstrate human BBB transport, clinical neuroprotection or neuronal target engagement.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Rats given purified indicaxanthin

plain_language

After oral indicaxanthin, rat whole-brain content peaked at 20 +/- 2.4 ng at 2.5 hours.

primary_references

Indicaxanthin from Opuntia ficus-indica Crosses the Blood-Brain Barrier and Modulates Neuronal Bioelectric Activity in Rat Hippocampus at Dietary-Consistent Amounts. (2015). https://pubmed.ncbi.nlm.nih.gov/26227670/ DOI: 10.1021/acs.jafc.5b02612

route

Oral administration

tissue

Whole brain

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 195–204

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Rats given purified indicaxanthin · source_derived_draft · unverified_draft

## indicaxanthin-rat-brain-exposure After oral indicaxanthin, rat whole-brain content peaked at 20 +/- 2.4 ng at 2.5 hours. Model/species: Rats given purified indicaxanthin Tissue: Whole brain Exposure: Indicaxanthin 2 micromol/kg Route: Oral administration Duration: Detected within 1 h, peak at 2.5 h, disappearance by approximately 4 h Limits: Brain exposure in rats does not demonstrate human BBB transport, clinical neuroprotection or neuronal target engagement. Primary reference: Indicaxanthin from Opuntia ficus-indica Crosses the Blood-Brain Barrier and Modulates Neuronal Bioelectric Activity in Rat Hippocampus at Dietary-Consistent Amounts. (2015). https://pubmed.ncbi.nlm.nih.gov/26227670/ DOI: 10.1021/acs.jafc.5b02612 Access: Primary PubMed abstract.

dose

Indicaxanthin 0.085, 0.17 and 0.34 ng/neuron

duration

Acute recording; local application for 5 min

evidence_access

Primary PubMed abstract; 2018 regional neuronal results additionally inspected in PMC full text.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

In vivo rat single-neuron recordings

limitations

Effects varied by region and dose. Direct striatal application produced effects even though oral-dose tissue analysis did not detect pigment there.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

In vivo rat single-neuron recordings

plain_language

Local indicaxanthin reduced cortical-neuron firing at the two higher tested amounts in rats.

primary_references

Brain Distribution and Modulation of Neuronal Excitability by Indicaxanthin From Opuntia Ficus Indica Administered at Nutritionally-Relevant Amounts. (2018). https://pubmed.ncbi.nlm.nih.gov/29867444/ DOI: 10.3389/fnagi.2018.00133

route

Local microiontophoresis

tissue

Cortex and striatum

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 239–248

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · In vivo rat single-neuron recordings · source_derived_draft · unverified_draft

## indicaxanthin-rat-cortical-firing Local indicaxanthin reduced cortical-neuron firing at the two higher tested amounts in rats. Model/species: In vivo rat single-neuron recordings Tissue: Cortex and striatum Exposure: Indicaxanthin 0.085, 0.17 and 0.34 ng/neuron Route: Local microiontophoresis Duration: Acute recording; local application for 5 min Limits: Effects varied by region and dose. Direct striatal application produced effects even though oral-dose tissue analysis did not detect pigment there. Primary reference: Brain Distribution and Modulation of Neuronal Excitability by Indicaxanthin From Opuntia Ficus Indica Administered at Nutritionally-Relevant Amounts. (2018). https://pubmed.ncbi.nlm.nih.gov/29867444/ DOI: 10.3389/fnagi.2018.00133 Access: Primary PubMed abstract; 2018 regional neuronal results additionally inspected in PMC full text.

dose

Indicaxanthin 0.085-0.34 ng/neuron; glutamate challenge in selected recordings

duration

Acute firing measurements

evidence_access

Primary PubMed abstract.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

In vivo rat hippocampal single-neuron recordings

limitations

Local application bypasses oral distribution. NMDAR binding was proposed by modeling, not established by this electrophysiological observation.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

In vivo rat hippocampal single-neuron recordings

plain_language

Local indicaxanthin at 0.34 ng/neuron reduced glutamate-evoked excitation in rat hippocampal recordings.

primary_references

Indicaxanthin from Opuntia ficus-indica Crosses the Blood-Brain Barrier and Modulates Neuronal Bioelectric Activity in Rat Hippocampus at Dietary-Consistent Amounts. (2015). https://pubmed.ncbi.nlm.nih.gov/26227670/ DOI: 10.1021/acs.jafc.5b02612

route

Local microiontophoresis

tissue

Hippocampus

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 217–226

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · In vivo rat hippocampal single-neuron recordings · source_derived_draft · unverified_draft

## indicaxanthin-rat-glutamate-excitation Local indicaxanthin at 0.34 ng/neuron reduced glutamate-evoked excitation in rat hippocampal recordings. Model/species: In vivo rat hippocampal single-neuron recordings Tissue: Hippocampus Exposure: Indicaxanthin 0.085-0.34 ng/neuron; glutamate challenge in selected recordings Route: Local microiontophoresis Duration: Acute firing measurements Limits: Local application bypasses oral distribution. NMDAR binding was proposed by modeling, not established by this electrophysiological observation. Primary reference: Indicaxanthin from Opuntia ficus-indica Crosses the Blood-Brain Barrier and Modulates Neuronal Bioelectric Activity in Rat Hippocampus at Dietary-Consistent Amounts. (2015). https://pubmed.ncbi.nlm.nih.gov/26227670/ DOI: 10.1021/acs.jafc.5b02612 Access: Primary PubMed abstract.

dose

Indicaxanthin 0.085-0.34 ng/neuron; glutamate challenge in selected recordings

duration

Acute firing measurements

evidence_access

Primary PubMed abstract.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

In vivo rat hippocampal single-neuron recordings

limitations

Local application bypasses oral distribution. NMDAR binding was proposed by modeling, not established by this electrophysiological observation.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

In vivo rat hippocampal single-neuron recordings

plain_language

Local indicaxanthin application reduced spontaneous firing of rat hippocampal neurons in a dose-related manner.

primary_references

Indicaxanthin from Opuntia ficus-indica Crosses the Blood-Brain Barrier and Modulates Neuronal Bioelectric Activity in Rat Hippocampus at Dietary-Consistent Amounts. (2015). https://pubmed.ncbi.nlm.nih.gov/26227670/ DOI: 10.1021/acs.jafc.5b02612

route

Local microiontophoresis

tissue

Hippocampus

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 206–215

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · In vivo rat hippocampal single-neuron recordings · source_derived_draft · unverified_draft

## indicaxanthin-rat-hippocampal-firing Local indicaxanthin application reduced spontaneous firing of rat hippocampal neurons in a dose-related manner. Model/species: In vivo rat hippocampal single-neuron recordings Tissue: Hippocampus Exposure: Indicaxanthin 0.085-0.34 ng/neuron; glutamate challenge in selected recordings Route: Local microiontophoresis Duration: Acute firing measurements Limits: Local application bypasses oral distribution. NMDAR binding was proposed by modeling, not established by this electrophysiological observation. Primary reference: Indicaxanthin from Opuntia ficus-indica Crosses the Blood-Brain Barrier and Modulates Neuronal Bioelectric Activity in Rat Hippocampus at Dietary-Consistent Amounts. (2015). https://pubmed.ncbi.nlm.nih.gov/26227670/ DOI: 10.1021/acs.jafc.5b02612 Access: Primary PubMed abstract.

dose

Indicaxanthin 2 micromol/kg

duration

Tissue sampling 1 h after dosing

evidence_access

Primary PubMed abstract; 2018 regional neuronal results additionally inspected in PMC full text.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Rats given purified indicaxanthin

limitations

Measured regional distribution must not be conflated with local-injection electrophysiology; human brain exposure is unproven.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Rats given purified indicaxanthin

plain_language

After oral indicaxanthin, pigment was detected in rat cortex, hippocampus, diencephalon, brainstem and cerebellum, but not the striato-pallidal complex.

primary_references

Brain Distribution and Modulation of Neuronal Excitability by Indicaxanthin From Opuntia Ficus Indica Administered at Nutritionally-Relevant Amounts. (2018). https://pubmed.ncbi.nlm.nih.gov/29867444/ DOI: 10.3389/fnagi.2018.00133

route

Oral administration

tissue

Regional brain tissue

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 228–237

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Rats given purified indicaxanthin · source_derived_draft · unverified_draft

## indicaxanthin-rat-regional-distribution After oral indicaxanthin, pigment was detected in rat cortex, hippocampus, diencephalon, brainstem and cerebellum, but not the striato-pallidal complex. Model/species: Rats given purified indicaxanthin Tissue: Regional brain tissue Exposure: Indicaxanthin 2 micromol/kg Route: Oral administration Duration: Tissue sampling 1 h after dosing Limits: Measured regional distribution must not be conflated with local-injection electrophysiology; human brain exposure is unproven. Primary reference: Brain Distribution and Modulation of Neuronal Excitability by Indicaxanthin From Opuntia Ficus Indica Administered at Nutritionally-Relevant Amounts. (2018). https://pubmed.ncbi.nlm.nih.gov/29867444/ DOI: 10.3389/fnagi.2018.00133 Access: Primary PubMed abstract; 2018 regional neuronal results additionally inspected in PMC full text.

dose

Indicaxanthin 0.085, 0.17 and 0.34 ng/neuron

duration

Acute recording; local application for 5 min

evidence_access

Primary PubMed abstract; 2018 regional neuronal results additionally inspected in PMC full text.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

In vivo rat single-neuron recordings

limitations

Effects varied by region and dose. Direct striatal application produced effects even though oral-dose tissue analysis did not detect pigment there.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

In vivo rat single-neuron recordings

plain_language

Local indicaxanthin increased firing in rat striatal neurons, contrasting with its predominant inhibitory response in other recorded regions.

primary_references

Brain Distribution and Modulation of Neuronal Excitability by Indicaxanthin From Opuntia Ficus Indica Administered at Nutritionally-Relevant Amounts. (2018). https://pubmed.ncbi.nlm.nih.gov/29867444/ DOI: 10.3389/fnagi.2018.00133

route

Local microiontophoresis

tissue

Cortex and striatum

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 250–259

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · In vivo rat single-neuron recordings · source_derived_draft · unverified_draft

## indicaxanthin-rat-striatal-firing Local indicaxanthin increased firing in rat striatal neurons, contrasting with its predominant inhibitory response in other recorded regions. Model/species: In vivo rat single-neuron recordings Tissue: Cortex and striatum Exposure: Indicaxanthin 0.085, 0.17 and 0.34 ng/neuron Route: Local microiontophoresis Duration: Acute recording; local application for 5 min Limits: Effects varied by region and dose. Direct striatal application produced effects even though oral-dose tissue analysis did not detect pigment there. Primary reference: Brain Distribution and Modulation of Neuronal Excitability by Indicaxanthin From Opuntia Ficus Indica Administered at Nutritionally-Relevant Amounts. (2018). https://pubmed.ncbi.nlm.nih.gov/29867444/ DOI: 10.3389/fnagi.2018.00133 Access: Primary PubMed abstract; 2018 regional neuronal results additionally inspected in PMC full text.

dose

Indicaxanthin 1-10 micromolar; cumene hydroperoxide challenge

duration

Not specified in accessed abstract

evidence_access

Primary PubMed abstract.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human beta-thalassemia donor erythrocytes

limitations

Ex vivo redox protection is not demonstrated oral treatment of anemia; preservation is not proof of increased glutathione synthesis.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Human beta-thalassemia donor erythrocytes

plain_language

Added indicaxanthin delayed glutathione depletion during oxidative challenge of beta-thalassemic red cells.

primary_references

Cytoprotective effects of the antioxidant phytochemical indicaxanthin in beta-thalassemia red blood cells. (2006). https://pubmed.ncbi.nlm.nih.gov/16984002/ DOI: 10.1080/10715760600554228

route

Ex vivo addition

tissue

Red blood cells

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 41–50

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Human beta-thalassemia donor erythrocytes · source_derived_draft · unverified_draft

## indicaxanthin-rbc-glutathione Added indicaxanthin delayed glutathione depletion during oxidative challenge of beta-thalassemic red cells. Model/species: Human beta-thalassemia donor erythrocytes Tissue: Red blood cells Exposure: Indicaxanthin 1-10 micromolar; cumene hydroperoxide challenge Route: Ex vivo addition Duration: Not specified in accessed abstract Limits: Ex vivo redox protection is not demonstrated oral treatment of anemia; preservation is not proof of increased glutathione synthesis. Primary reference: Cytoprotective effects of the antioxidant phytochemical indicaxanthin in beta-thalassemia red blood cells. (2006). https://pubmed.ncbi.nlm.nih.gov/16984002/ DOI: 10.1080/10715760600554228 Access: Primary PubMed abstract.

dose

Indicaxanthin 1-10 micromolar; cumene hydroperoxide challenge

duration

Not specified in accessed abstract

evidence_access

Primary PubMed abstract.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human beta-thalassemia donor erythrocytes

limitations

Ex vivo redox protection is not demonstrated oral treatment of anemia; preservation is not proof of increased glutathione synthesis.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Human beta-thalassemia donor erythrocytes

plain_language

Added indicaxanthin increased resistance of beta-thalassemic red cells to peroxide-induced haemolysis.

primary_references

Cytoprotective effects of the antioxidant phytochemical indicaxanthin in beta-thalassemia red blood cells. (2006). https://pubmed.ncbi.nlm.nih.gov/16984002/ DOI: 10.1080/10715760600554228

route

Ex vivo addition

tissue

Red blood cells

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 19–28

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Human beta-thalassemia donor erythrocytes · source_derived_draft · unverified_draft

## indicaxanthin-rbc-haemolysis Added indicaxanthin increased resistance of beta-thalassemic red cells to peroxide-induced haemolysis. Model/species: Human beta-thalassemia donor erythrocytes Tissue: Red blood cells Exposure: Indicaxanthin 1-10 micromolar; cumene hydroperoxide challenge Route: Ex vivo addition Duration: Not specified in accessed abstract Limits: Ex vivo redox protection is not demonstrated oral treatment of anemia; preservation is not proof of increased glutathione synthesis. Primary reference: Cytoprotective effects of the antioxidant phytochemical indicaxanthin in beta-thalassemia red blood cells. (2006). https://pubmed.ncbi.nlm.nih.gov/16984002/ DOI: 10.1080/10715760600554228 Access: Primary PubMed abstract.

dose

Indicaxanthin 1-10 micromolar; cumene hydroperoxide challenge

duration

Not specified in accessed abstract

evidence_access

Primary PubMed abstract.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human beta-thalassemia donor erythrocytes

limitations

Ex vivo redox protection is not demonstrated oral treatment of anemia; preservation is not proof of increased glutathione synthesis.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Human beta-thalassemia donor erythrocytes

plain_language

Added indicaxanthin delayed vitamin E depletion during oxidative challenge of beta-thalassemic red cells.

primary_references

Cytoprotective effects of the antioxidant phytochemical indicaxanthin in beta-thalassemia red blood cells. (2006). https://pubmed.ncbi.nlm.nih.gov/16984002/ DOI: 10.1080/10715760600554228

route

Ex vivo addition

tissue

Red blood cells

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 30–39

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Human beta-thalassemia donor erythrocytes · source_derived_draft · unverified_draft

## indicaxanthin-rbc-vitamin-e Added indicaxanthin delayed vitamin E depletion during oxidative challenge of beta-thalassemic red cells. Model/species: Human beta-thalassemia donor erythrocytes Tissue: Red blood cells Exposure: Indicaxanthin 1-10 micromolar; cumene hydroperoxide challenge Route: Ex vivo addition Duration: Not specified in accessed abstract Limits: Ex vivo redox protection is not demonstrated oral treatment of anemia; preservation is not proof of increased glutathione synthesis. Primary reference: Cytoprotective effects of the antioxidant phytochemical indicaxanthin in beta-thalassemia red blood cells. (2006). https://pubmed.ncbi.nlm.nih.gov/16984002/ DOI: 10.1080/10715760600554228 Access: Primary PubMed abstract.

dose

Indicaxanthin 10 and 50 micromolar analysis; study also includes 100 micromolar

duration

48 h

evidence_access

Primary open full text, relevant results/methods and PubMed metadata.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human Caco-2 colorectal cancer cells; RRBS analysis

limitations

Same research program and related RRBS methods as the 2023 study; independent dataset replication is not established. rDNA methylation is not direct proof of reduced ribosome production or cell transdifferentiation.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Human Caco-2 colorectal cancer cells; RRBS analysis

plain_language

The 2025 Caco-2 methylome analysis associated indicaxanthin exposure with increased methylation at rDNA loci.

primary_references

Epigenetic Remodeling of Regulatory Regions by Indicaxanthin Suggests a Shift in Cell Identity Programs in Colorectal Cancer Cells. (2025). https://pubmed.ncbi.nlm.nih.gov/40649850/ DOI: 10.3390/ijms26136072

route

In vitro treatment and methylome analysis

tissue

rDNA loci and regulatory DNA

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 459–468

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Human Caco-2 colorectal cancer cells; RRBS analysis · source_derived_draft · unverified_draft

## indicaxanthin-rdna-methylation The 2025 Caco-2 methylome analysis associated indicaxanthin exposure with increased methylation at rDNA loci. Model/species: Human Caco-2 colorectal cancer cells; RRBS analysis Tissue: rDNA loci and regulatory DNA Exposure: Indicaxanthin 10 and 50 micromolar analysis; study also includes 100 micromolar Route: In vitro treatment and methylome analysis Duration: 48 h Limits: Same research program and related RRBS methods as the 2023 study; independent dataset replication is not established. rDNA methylation is not direct proof of reduced ribosome production or cell transdifferentiation. Primary reference: Epigenetic Remodeling of Regulatory Regions by Indicaxanthin Suggests a Shift in Cell Identity Programs in Colorectal Cancer Cells. (2025). https://pubmed.ncbi.nlm.nih.gov/40649850/ DOI: 10.3390/ijms26136072 Access: Primary open full text, relevant results/methods and PubMed metadata.

dose

Indicaxanthin 5-25 micromolar with IL-1beta 25 ng/mL

duration

24 h for mediator release and permeability; earlier signaling assays

evidence_access

Primary PubMed abstract; detailed exposure for PMID 23931157 additionally checked in publisher results. No uninspected full text is claimed.

evidence_scope

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

experimental_model

Differentiated human Caco-2 intestinal epithelial monolayers

limitations

No clinical IBD treatment effect or molecular binding site was established. Total thiols must not be relabeled as a specific glutathione measurement.

nutrient_topic

Betalains collection; each molecular form, species, exposure and preparation remains explicit. · Betalains

organism

Differentiated human Caco-2 intestinal epithelial monolayers

plain_language

Indicaxanthin prevented the increase in epithelial permeability caused by IL-1beta.

primary_references

Indicaxanthin inhibits NADPH oxidase (NOX)-1 activation and NF-κB-dependent release of inflammatory mediators and prevents the increase of epithelial permeability in IL-1β-exposed Caco-2 cells. (2014). https://pubmed.ncbi.nlm.nih.gov/23931157/ DOI: 10.1017/S0007114513002663

route

In vitro co-incubation

tissue

Intestinal epithelial model

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 317–325

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Differentiated human Caco-2 intestinal epithelial monolayers · source_derived_draft · unverified_draft

## betalains-caco2-barrier Indicaxanthin prevented the increase in epithelial permeability caused by IL-1beta. Model/species: Differentiated human Caco-2 intestinal epithelial monolayers Tissue: Intestinal epithelial model Exposure: Indicaxanthin 5-25 micromolar with IL-1beta 25 ng/mL Route: In vitro co-incubation Duration: 24 h for mediator release and permeability; earlier signaling assays Limits: No clinical IBD treatment effect or molecular binding site was established. Total thiols must not be relabeled as a specific glutathione measurement. Primary reference: Indicaxanthin inhibits NADPH oxidase (NOX)-1 activation and NF-κB-dependent release of inflammatory mediators and prevents the increase of epithelial permeability in IL-1β-exposed Caco-2 cells. (2014). https://pubmed.ncbi.nlm.nih.gov/23931157/ DOI: 10.1017/S0007114513002663

dose

Indicaxanthin 5-25 micromolar with IL-1beta 25 ng/mL

duration

24 h for mediator release and permeability; earlier signaling assays

evidence_access

Primary PubMed abstract; detailed exposure for PMID 23931157 additionally checked in publisher results. No uninspected full text is claimed.

evidence_scope

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

experimental_model

Differentiated human Caco-2 intestinal epithelial monolayers

limitations

No clinical IBD treatment effect or molecular binding site was established. Total thiols must not be relabeled as a specific glutathione measurement.

nutrient_topic

Betalains collection; each molecular form, species, exposure and preparation remains explicit. · Betalains

organism

Differentiated human Caco-2 intestinal epithelial monolayers

plain_language

Indicaxanthin reduced induced COX-2 expression in IL-1beta-exposed Caco-2 cells.

primary_references

Indicaxanthin inhibits NADPH oxidase (NOX)-1 activation and NF-κB-dependent release of inflammatory mediators and prevents the increase of epithelial permeability in IL-1β-exposed Caco-2 cells. (2014). https://pubmed.ncbi.nlm.nih.gov/23931157/ DOI: 10.1017/S0007114513002663

route

In vitro co-incubation

tissue

Intestinal epithelial model

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 277–285

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Differentiated human Caco-2 intestinal epithelial monolayers · source_derived_draft · unverified_draft

## betalains-caco2-cox2 Indicaxanthin reduced induced COX-2 expression in IL-1beta-exposed Caco-2 cells. Model/species: Differentiated human Caco-2 intestinal epithelial monolayers Tissue: Intestinal epithelial model Exposure: Indicaxanthin 5-25 micromolar with IL-1beta 25 ng/mL Route: In vitro co-incubation Duration: 24 h for mediator release and permeability; earlier signaling assays Limits: No clinical IBD treatment effect or molecular binding site was established. Total thiols must not be relabeled as a specific glutathione measurement. Primary reference: Indicaxanthin inhibits NADPH oxidase (NOX)-1 activation and NF-κB-dependent release of inflammatory mediators and prevents the increase of epithelial permeability in IL-1β-exposed Caco-2 cells. (2014). https://pubmed.ncbi.nlm.nih.gov/23931157/ DOI: 10.1017/S0007114513002663

dose

Indicaxanthin 5-25 micromolar with IL-1beta 25 ng/mL

duration

24 h for mediator release and permeability; earlier signaling assays

evidence_access

Primary PubMed abstract; detailed exposure for PMID 23931157 additionally checked in publisher results. No uninspected full text is claimed.

evidence_scope

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

experimental_model

Differentiated human Caco-2 intestinal epithelial monolayers

limitations

No clinical IBD treatment effect or molecular binding site was established. Total thiols must not be relabeled as a specific glutathione measurement.

nutrient_topic

Betalains collection; each molecular form, species, exposure and preparation remains explicit. · Betalains

organism

Differentiated human Caco-2 intestinal epithelial monolayers

plain_language

Indicaxanthin co-treatment suppressed IL-1beta-induced NF-kappaB activation.

primary_references

Indicaxanthin inhibits NADPH oxidase (NOX)-1 activation and NF-κB-dependent release of inflammatory mediators and prevents the increase of epithelial permeability in IL-1β-exposed Caco-2 cells. (2014). https://pubmed.ncbi.nlm.nih.gov/23931157/ DOI: 10.1017/S0007114513002663

route

In vitro co-incubation

tissue

Intestinal epithelial model

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 267–275

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Differentiated human Caco-2 intestinal epithelial monolayers · source_derived_draft · unverified_draft

## betalains-caco2-nfkb Indicaxanthin co-treatment suppressed IL-1beta-induced NF-kappaB activation. Model/species: Differentiated human Caco-2 intestinal epithelial monolayers Tissue: Intestinal epithelial model Exposure: Indicaxanthin 5-25 micromolar with IL-1beta 25 ng/mL Route: In vitro co-incubation Duration: 24 h for mediator release and permeability; earlier signaling assays Limits: No clinical IBD treatment effect or molecular binding site was established. Total thiols must not be relabeled as a specific glutathione measurement. Primary reference: Indicaxanthin inhibits NADPH oxidase (NOX)-1 activation and NF-κB-dependent release of inflammatory mediators and prevents the increase of epithelial permeability in IL-1β-exposed Caco-2 cells. (2014). https://pubmed.ncbi.nlm.nih.gov/23931157/ DOI: 10.1017/S0007114513002663

dose

Indicaxanthin 5-25 micromolar with IL-1beta 25 ng/mL

duration

24 h for mediator release and permeability; earlier signaling assays

evidence_access

Primary PubMed abstract; detailed exposure for PMID 23931157 additionally checked in publisher results. No uninspected full text is claimed.

evidence_scope

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

experimental_model

Differentiated human Caco-2 intestinal epithelial monolayers

limitations

No clinical IBD treatment effect or molecular binding site was established. Total thiols must not be relabeled as a specific glutathione measurement.

nutrient_topic

Betalains collection; each molecular form, species, exposure and preparation remains explicit. · Betalains

organism

Differentiated human Caco-2 intestinal epithelial monolayers

plain_language

Indicaxanthin reduced induced nitric oxide synthase expression in IL-1beta-exposed Caco-2 cells.

primary_references

Indicaxanthin inhibits NADPH oxidase (NOX)-1 activation and NF-κB-dependent release of inflammatory mediators and prevents the increase of epithelial permeability in IL-1β-exposed Caco-2 cells. (2014). https://pubmed.ncbi.nlm.nih.gov/23931157/ DOI: 10.1017/S0007114513002663

route

In vitro co-incubation

tissue

Intestinal epithelial model

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 287–295

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Differentiated human Caco-2 intestinal epithelial monolayers · source_derived_draft · unverified_draft

## betalains-caco2-nos2 Indicaxanthin reduced induced nitric oxide synthase expression in IL-1beta-exposed Caco-2 cells. Model/species: Differentiated human Caco-2 intestinal epithelial monolayers Tissue: Intestinal epithelial model Exposure: Indicaxanthin 5-25 micromolar with IL-1beta 25 ng/mL Route: In vitro co-incubation Duration: 24 h for mediator release and permeability; earlier signaling assays Limits: No clinical IBD treatment effect or molecular binding site was established. Total thiols must not be relabeled as a specific glutathione measurement. Primary reference: Indicaxanthin inhibits NADPH oxidase (NOX)-1 activation and NF-κB-dependent release of inflammatory mediators and prevents the increase of epithelial permeability in IL-1β-exposed Caco-2 cells. (2014). https://pubmed.ncbi.nlm.nih.gov/23931157/ DOI: 10.1017/S0007114513002663

dose

Indicaxanthin 5-25 micromolar with IL-1beta 25 ng/mL

duration

24 h for mediator release and permeability; earlier signaling assays

evidence_access

Primary PubMed abstract; detailed exposure for PMID 23931157 additionally checked in publisher results. No uninspected full text is claimed.

evidence_scope

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

experimental_model

Differentiated human Caco-2 intestinal epithelial monolayers

limitations

No clinical IBD treatment effect or molecular binding site was established. Total thiols must not be relabeled as a specific glutathione measurement.

nutrient_topic

Betalains collection; each molecular form, species, exposure and preparation remains explicit. · Betalains

organism

Differentiated human Caco-2 intestinal epithelial monolayers

plain_language

Indicaxanthin co-treatment prevented IL-1beta-induced NOX1 activation in Caco-2 monolayers.

primary_references

Indicaxanthin inhibits NADPH oxidase (NOX)-1 activation and NF-κB-dependent release of inflammatory mediators and prevents the increase of epithelial permeability in IL-1β-exposed Caco-2 cells. (2014). https://pubmed.ncbi.nlm.nih.gov/23931157/ DOI: 10.1017/S0007114513002663

route

In vitro co-incubation

tissue

Intestinal epithelial model

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 257–265

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Differentiated human Caco-2 intestinal epithelial monolayers · source_derived_draft · unverified_draft

## betalains-caco2-nox1 Indicaxanthin co-treatment prevented IL-1beta-induced NOX1 activation in Caco-2 monolayers. Model/species: Differentiated human Caco-2 intestinal epithelial monolayers Tissue: Intestinal epithelial model Exposure: Indicaxanthin 5-25 micromolar with IL-1beta 25 ng/mL Route: In vitro co-incubation Duration: 24 h for mediator release and permeability; earlier signaling assays Limits: No clinical IBD treatment effect or molecular binding site was established. Total thiols must not be relabeled as a specific glutathione measurement. Primary reference: Indicaxanthin inhibits NADPH oxidase (NOX)-1 activation and NF-κB-dependent release of inflammatory mediators and prevents the increase of epithelial permeability in IL-1β-exposed Caco-2 cells. (2014). https://pubmed.ncbi.nlm.nih.gov/23931157/ DOI: 10.1017/S0007114513002663

dose

Indicaxanthin 5-25 micromolar with IL-1beta 25 ng/mL

duration

24 h for mediator release and permeability; earlier signaling assays

evidence_access

Primary PubMed abstract; detailed exposure for PMID 23931157 additionally checked in publisher results. No uninspected full text is claimed.

evidence_scope

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

experimental_model

Differentiated human Caco-2 intestinal epithelial monolayers

limitations

No clinical IBD treatment effect or molecular binding site was established. Total thiols must not be relabeled as a specific glutathione measurement.

nutrient_topic

Betalains collection; each molecular form, species, exposure and preparation remains explicit. · Betalains

organism

Differentiated human Caco-2 intestinal epithelial monolayers

plain_language

Indicaxanthin prevented the IL-1beta-associated rise in cellular oxidant signal.

primary_references

Indicaxanthin inhibits NADPH oxidase (NOX)-1 activation and NF-κB-dependent release of inflammatory mediators and prevents the increase of epithelial permeability in IL-1β-exposed Caco-2 cells. (2014). https://pubmed.ncbi.nlm.nih.gov/23931157/ DOI: 10.1017/S0007114513002663

route

In vitro co-incubation

tissue

Intestinal epithelial model

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 297–305

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Differentiated human Caco-2 intestinal epithelial monolayers · source_derived_draft · unverified_draft

## betalains-caco2-ros Indicaxanthin prevented the IL-1beta-associated rise in cellular oxidant signal. Model/species: Differentiated human Caco-2 intestinal epithelial monolayers Tissue: Intestinal epithelial model Exposure: Indicaxanthin 5-25 micromolar with IL-1beta 25 ng/mL Route: In vitro co-incubation Duration: 24 h for mediator release and permeability; earlier signaling assays Limits: No clinical IBD treatment effect or molecular binding site was established. Total thiols must not be relabeled as a specific glutathione measurement. Primary reference: Indicaxanthin inhibits NADPH oxidase (NOX)-1 activation and NF-κB-dependent release of inflammatory mediators and prevents the increase of epithelial permeability in IL-1β-exposed Caco-2 cells. (2014). https://pubmed.ncbi.nlm.nih.gov/23931157/ DOI: 10.1017/S0007114513002663

dose

Indicaxanthin 5-25 micromolar with IL-1beta 25 ng/mL

duration

24 h for mediator release and permeability; earlier signaling assays

evidence_access

Primary PubMed abstract; detailed exposure for PMID 23931157 additionally checked in publisher results. No uninspected full text is claimed.

evidence_scope

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

experimental_model

Differentiated human Caco-2 intestinal epithelial monolayers

limitations

No clinical IBD treatment effect or molecular binding site was established. Total thiols must not be relabeled as a specific glutathione measurement.

nutrient_topic

Betalains collection; each molecular form, species, exposure and preparation remains explicit. · Betalains

organism

Differentiated human Caco-2 intestinal epithelial monolayers

plain_language

Indicaxanthin prevented IL-1beta-associated loss of total cellular thiols.

primary_references

Indicaxanthin inhibits NADPH oxidase (NOX)-1 activation and NF-κB-dependent release of inflammatory mediators and prevents the increase of epithelial permeability in IL-1β-exposed Caco-2 cells. (2014). https://pubmed.ncbi.nlm.nih.gov/23931157/ DOI: 10.1017/S0007114513002663

route

In vitro co-incubation

tissue

Intestinal epithelial model

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 307–315

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Differentiated human Caco-2 intestinal epithelial monolayers · source_derived_draft · unverified_draft

## betalains-caco2-thiols Indicaxanthin prevented IL-1beta-associated loss of total cellular thiols. Model/species: Differentiated human Caco-2 intestinal epithelial monolayers Tissue: Intestinal epithelial model Exposure: Indicaxanthin 5-25 micromolar with IL-1beta 25 ng/mL Route: In vitro co-incubation Duration: 24 h for mediator release and permeability; earlier signaling assays Limits: No clinical IBD treatment effect or molecular binding site was established. Total thiols must not be relabeled as a specific glutathione measurement. Primary reference: Indicaxanthin inhibits NADPH oxidase (NOX)-1 activation and NF-κB-dependent release of inflammatory mediators and prevents the increase of epithelial permeability in IL-1β-exposed Caco-2 cells. (2014). https://pubmed.ncbi.nlm.nih.gov/23931157/ DOI: 10.1017/S0007114513002663

dose

Micromolar substrates; concentration-dependent chlorination assays

duration

Rapid kinetic measurements at 25 degrees C; pH 7.0 and pH 5.0

evidence_access

Primary PubMed abstract; detailed exposure for PMID 23931157 additionally checked in publisher results. No uninspected full text is claimed.

evidence_scope

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

experimental_model

Purified human myeloperoxidase; cell-free chemistry

limitations

MPO substrates can stimulate or inhibit chlorination depending on conditions; not a universal MPO inhibitor.

nutrient_topic

Betalains collection; each molecular form, species, exposure and preparation remains explicit. · Betalains

organism

Purified human myeloperoxidase; cell-free chemistry

plain_language

Indicaxanthin stimulated or inhibited MPO chlorination at neutral pH depending on concentration; at pH 5 only inhibition was observed.

primary_references

Mechanism of interaction of betanin and indicaxanthin with human myeloperoxidase and hypochlorous acid. (2005). https://pubmed.ncbi.nlm.nih.gov/15913556/ DOI: 10.1016/j.bbrc.2005.05.031

route

In vitro reagent addition

tissue

MPO redox cycle and HOCl solution

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 177–185

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Purified human myeloperoxidase; cell-free chemistry · source_derived_draft · unverified_draft

## betalains-indicaxanthin-chlorination Indicaxanthin stimulated or inhibited MPO chlorination at neutral pH depending on concentration; at pH 5 only inhibition was observed. Model/species: Purified human myeloperoxidase; cell-free chemistry Tissue: MPO redox cycle and HOCl solution Exposure: Micromolar substrates; concentration-dependent chlorination assays Route: In vitro reagent addition Duration: Rapid kinetic measurements at 25 degrees C; pH 7.0 and pH 5.0 Limits: MPO substrates can stimulate or inhibit chlorination depending on conditions; not a universal MPO inhibitor. Primary reference: Mechanism of interaction of betanin and indicaxanthin with human myeloperoxidase and hypochlorous acid. (2005). https://pubmed.ncbi.nlm.nih.gov/15913556/ DOI: 10.1016/j.bbrc.2005.05.031

dose

Micromolar substrates; concentration-dependent chlorination assays

duration

Rapid kinetic measurements at 25 degrees C; pH 7.0 and pH 5.0

evidence_access

Primary PubMed abstract; detailed exposure for PMID 23931157 additionally checked in publisher results. No uninspected full text is claimed.

evidence_scope

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

experimental_model

Purified human myeloperoxidase; cell-free chemistry

limitations

MPO substrates can stimulate or inhibit chlorination depending on conditions; not a universal MPO inhibitor.

nutrient_topic

Betalains collection; each molecular form, species, exposure and preparation remains explicit. · Betalains

organism

Purified human myeloperoxidase; cell-free chemistry

plain_language

Indicaxanthin reacted directly with hypochlorous acid in the kinetic assay.

primary_references

Mechanism of interaction of betanin and indicaxanthin with human myeloperoxidase and hypochlorous acid. (2005). https://pubmed.ncbi.nlm.nih.gov/15913556/ DOI: 10.1016/j.bbrc.2005.05.031

route

In vitro reagent addition

tissue

MPO redox cycle and HOCl solution

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 167–175

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Purified human myeloperoxidase; cell-free chemistry · source_derived_draft · unverified_draft

## betalains-indicaxanthin-hocl Indicaxanthin reacted directly with hypochlorous acid in the kinetic assay. Model/species: Purified human myeloperoxidase; cell-free chemistry Tissue: MPO redox cycle and HOCl solution Exposure: Micromolar substrates; concentration-dependent chlorination assays Route: In vitro reagent addition Duration: Rapid kinetic measurements at 25 degrees C; pH 7.0 and pH 5.0 Limits: MPO substrates can stimulate or inhibit chlorination depending on conditions; not a universal MPO inhibitor. Primary reference: Mechanism of interaction of betanin and indicaxanthin with human myeloperoxidase and hypochlorous acid. (2005). https://pubmed.ncbi.nlm.nih.gov/15913556/ DOI: 10.1016/j.bbrc.2005.05.031

dose

25-100 micromolar pigment added to plasma; copper-triggered LDL oxidation

duration

Kinetic oxidation assay; incubation duration not specified in accessed abstract

evidence_access

Primary PubMed abstract; detailed exposure for PMID 23931157 additionally checked in publisher results. No uninspected full text is claimed.

evidence_scope

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

experimental_model

Human pooled plasma from 10 healthy donors; isolated LDL

limitations

Plasma spiking exceeds typical dietary parent-pigment exposure; vitamin synergy refers only to this assay.

nutrient_topic

Betalains collection; each molecular form, species, exposure and preparation remains explicit. · Betalains

organism

Human pooled plasma from 10 healthy donors; isolated LDL

plain_language

Adding indicaxanthin to human plasma produced pigment-enriched LDL after particle isolation.

primary_references

Increased resistance to oxidation of betalain-enriched human low density lipoproteins. (2003). https://pubmed.ncbi.nlm.nih.gov/12868496/ DOI: 10.1080/1071576031000097490

route

Ex vivo spiking, not oral dosing

tissue

Plasma and LDL

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 67–75

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Human pooled plasma from 10 healthy donors; isolated LDL · source_derived_draft · unverified_draft

## betalains-indicaxanthin-ldl-binding Adding indicaxanthin to human plasma produced pigment-enriched LDL after particle isolation. Model/species: Human pooled plasma from 10 healthy donors; isolated LDL Tissue: Plasma and LDL Exposure: 25-100 micromolar pigment added to plasma; copper-triggered LDL oxidation Route: Ex vivo spiking, not oral dosing Duration: Kinetic oxidation assay; incubation duration not specified in accessed abstract Limits: Plasma spiking exceeds typical dietary parent-pigment exposure; vitamin synergy refers only to this assay. Primary reference: Increased resistance to oxidation of betalain-enriched human low density lipoproteins. (2003). https://pubmed.ncbi.nlm.nih.gov/12868496/ DOI: 10.1080/1071576031000097490

dose

25-100 micromolar pigment added to plasma; copper-triggered LDL oxidation

duration

Kinetic oxidation assay; incubation duration not specified in accessed abstract

evidence_access

Primary PubMed abstract; detailed exposure for PMID 23931157 additionally checked in publisher results. No uninspected full text is claimed.

evidence_scope

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

experimental_model

Human pooled plasma from 10 healthy donors; isolated LDL

limitations

Plasma spiking exceeds typical dietary parent-pigment exposure; vitamin synergy refers only to this assay.

nutrient_topic

Betalains collection; each molecular form, species, exposure and preparation remains explicit. · Betalains

organism

Human pooled plasma from 10 healthy donors; isolated LDL

plain_language

LDL enriched with indicaxanthin showed a longer lag before copper-induced oxidation.

primary_references

Increased resistance to oxidation of betalain-enriched human low density lipoproteins. (2003). https://pubmed.ncbi.nlm.nih.gov/12868496/ DOI: 10.1080/1071576031000097490

route

Ex vivo spiking, not oral dosing

tissue

Plasma and LDL

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 77–85

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Human pooled plasma from 10 healthy donors; isolated LDL · source_derived_draft · unverified_draft

## betalains-indicaxanthin-ldl-oxidation LDL enriched with indicaxanthin showed a longer lag before copper-induced oxidation. Model/species: Human pooled plasma from 10 healthy donors; isolated LDL Tissue: Plasma and LDL Exposure: 25-100 micromolar pigment added to plasma; copper-triggered LDL oxidation Route: Ex vivo spiking, not oral dosing Duration: Kinetic oxidation assay; incubation duration not specified in accessed abstract Limits: Plasma spiking exceeds typical dietary parent-pigment exposure; vitamin synergy refers only to this assay. Primary reference: Increased resistance to oxidation of betalain-enriched human low density lipoproteins. (2003). https://pubmed.ncbi.nlm.nih.gov/12868496/ DOI: 10.1080/1071576031000097490

dose

Individual pigments 1-100 micromolar; LPS inflammatory stimulation or hydrogen peroxide oxidative challenge

duration

Not specified in accessed primary abstract

evidence_access

Primary PubMed abstract; detailed exposure for PMID 23931157 additionally checked in publisher results. No uninspected full text is claimed.

evidence_scope

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

experimental_model

Mouse RAW 264.7 macrophages

limitations

Mouse-cell results are separate from human intestinal assays. Pro-oxidant effects under peroxide challenge do not imply every dietary exposure is harmful. Transcript measurement; not direct enzyme inhibition.

nutrient_topic

Betalains collection; each molecular form, species, exposure and preparation remains explicit. · Betalains

organism

Mouse RAW 264.7 macrophages

plain_language

Indicaxanthin lowered NOX2 mRNA in the stimulated murine macrophage comparison.

primary_references

Differential Effects of Betacyanin and Betaxanthin Pigments on Oxidative Stress and Inflammatory Response in Murine Macrophages. (2023). https://pubmed.ncbi.nlm.nih.gov/37203590/ DOI: 10.1002/mnfr.202200583

route

In vitro exposure

tissue

Macrophages

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 407–415

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Mouse RAW 264.7 macrophages · source_derived_draft · unverified_draft

## betalains-indicaxanthin-mouse-nox2 Indicaxanthin lowered NOX2 mRNA in the stimulated murine macrophage comparison. Model/species: Mouse RAW 264.7 macrophages Tissue: Macrophages Exposure: Individual pigments 1-100 micromolar; LPS inflammatory stimulation or hydrogen peroxide oxidative challenge Route: In vitro exposure Duration: Not specified in accessed primary abstract Limits: Mouse-cell results are separate from human intestinal assays. Pro-oxidant effects under peroxide challenge do not imply every dietary exposure is harmful. Transcript measurement; not direct enzyme inhibition. Primary reference: Differential Effects of Betacyanin and Betaxanthin Pigments on Oxidative Stress and Inflammatory Response in Murine Macrophages. (2023). https://pubmed.ncbi.nlm.nih.gov/37203590/ DOI: 10.1002/mnfr.202200583

dose

Individual pigments 1-100 micromolar; LPS inflammatory stimulation or hydrogen peroxide oxidative challenge

duration

Not specified in accessed primary abstract

evidence_access

Primary PubMed abstract; detailed exposure for PMID 23931157 additionally checked in publisher results. No uninspected full text is claimed.

evidence_scope

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

experimental_model

Mouse RAW 264.7 macrophages

limitations

Mouse-cell results are separate from human intestinal assays. Pro-oxidant effects under peroxide challenge do not imply every dietary exposure is harmful. Context difference from intestinal anti-inflammatory findings; not a contradiction or a universal pigment property.

nutrient_topic

Betalains collection; each molecular form, species, exposure and preparation remains explicit. · Betalains

organism

Mouse RAW 264.7 macrophages

plain_language

Indicaxanthin increased ROS beyond the hydrogen-peroxide-challenged level in RAW 264.7 cells.

primary_references

Differential Effects of Betacyanin and Betaxanthin Pigments on Oxidative Stress and Inflammatory Response in Murine Macrophages. (2023). https://pubmed.ncbi.nlm.nih.gov/37203590/ DOI: 10.1002/mnfr.202200583

route

In vitro exposure

tissue

Macrophages

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 437–445

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Mouse RAW 264.7 macrophages · source_derived_draft · unverified_draft

## betalains-indicaxanthin-mouse-prooxidant Indicaxanthin increased ROS beyond the hydrogen-peroxide-challenged level in RAW 264.7 cells. Model/species: Mouse RAW 264.7 macrophages Tissue: Macrophages Exposure: Individual pigments 1-100 micromolar; LPS inflammatory stimulation or hydrogen peroxide oxidative challenge Route: In vitro exposure Duration: Not specified in accessed primary abstract Limits: Mouse-cell results are separate from human intestinal assays. Pro-oxidant effects under peroxide challenge do not imply every dietary exposure is harmful. Context difference from intestinal anti-inflammatory findings; not a contradiction or a universal pigment property. Primary reference: Differential Effects of Betacyanin and Betaxanthin Pigments on Oxidative Stress and Inflammatory Response in Murine Macrophages. (2023). https://pubmed.ncbi.nlm.nih.gov/37203590/ DOI: 10.1002/mnfr.202200583

dose

Micromolar substrates; concentration-dependent chlorination assays

duration

Rapid kinetic measurements at 25 degrees C; pH 7.0 and pH 5.0

evidence_access

Primary PubMed abstract; detailed exposure for PMID 23931157 additionally checked in publisher results. No uninspected full text is claimed.

evidence_scope

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

experimental_model

Purified human myeloperoxidase; cell-free chemistry

limitations

MPO substrates can stimulate or inhibit chlorination depending on conditions; not a universal MPO inhibitor. Negative direction denotes consumption of compound I, not overall inhibition of MPO.

nutrient_topic

Betalains collection; each molecular form, species, exposure and preparation remains explicit. · Betalains

organism

Purified human myeloperoxidase; cell-free chemistry

plain_language

Indicaxanthin donated one electron to MPO compound I, producing compound II.

primary_references

Mechanism of interaction of betanin and indicaxanthin with human myeloperoxidase and hypochlorous acid. (2005). https://pubmed.ncbi.nlm.nih.gov/15913556/ DOI: 10.1016/j.bbrc.2005.05.031

route

In vitro reagent addition

tissue

MPO redox cycle and HOCl solution

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 147–155

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Purified human myeloperoxidase; cell-free chemistry · source_derived_draft · unverified_draft

## betalains-indicaxanthin-mpo-i Indicaxanthin donated one electron to MPO compound I, producing compound II. Model/species: Purified human myeloperoxidase; cell-free chemistry Tissue: MPO redox cycle and HOCl solution Exposure: Micromolar substrates; concentration-dependent chlorination assays Route: In vitro reagent addition Duration: Rapid kinetic measurements at 25 degrees C; pH 7.0 and pH 5.0 Limits: MPO substrates can stimulate or inhibit chlorination depending on conditions; not a universal MPO inhibitor. Negative direction denotes consumption of compound I, not overall inhibition of MPO. Primary reference: Mechanism of interaction of betanin and indicaxanthin with human myeloperoxidase and hypochlorous acid. (2005). https://pubmed.ncbi.nlm.nih.gov/15913556/ DOI: 10.1016/j.bbrc.2005.05.031

dose

Micromolar substrates; concentration-dependent chlorination assays

duration

Rapid kinetic measurements at 25 degrees C; pH 7.0 and pH 5.0

evidence_access

Primary PubMed abstract; detailed exposure for PMID 23931157 additionally checked in publisher results. No uninspected full text is claimed.

evidence_scope

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

experimental_model

Purified human myeloperoxidase; cell-free chemistry

limitations

MPO substrates can stimulate or inhibit chlorination depending on conditions; not a universal MPO inhibitor. Negative direction denotes consumption of compound II; this step can restore chlorination activity.

nutrient_topic

Betalains collection; each molecular form, species, exposure and preparation remains explicit. · Betalains

organism

Purified human myeloperoxidase; cell-free chemistry

plain_language

Indicaxanthin reduced MPO compound II to the native ferric enzyme.

primary_references

Mechanism of interaction of betanin and indicaxanthin with human myeloperoxidase and hypochlorous acid. (2005). https://pubmed.ncbi.nlm.nih.gov/15913556/ DOI: 10.1016/j.bbrc.2005.05.031

route

In vitro reagent addition

tissue

MPO redox cycle and HOCl solution

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 157–165

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Purified human myeloperoxidase; cell-free chemistry · source_derived_draft · unverified_draft

## betalains-indicaxanthin-mpo-ii Indicaxanthin reduced MPO compound II to the native ferric enzyme. Model/species: Purified human myeloperoxidase; cell-free chemistry Tissue: MPO redox cycle and HOCl solution Exposure: Micromolar substrates; concentration-dependent chlorination assays Route: In vitro reagent addition Duration: Rapid kinetic measurements at 25 degrees C; pH 7.0 and pH 5.0 Limits: MPO substrates can stimulate or inhibit chlorination depending on conditions; not a universal MPO inhibitor. Negative direction denotes consumption of compound II; this step can restore chlorination activity. Primary reference: Mechanism of interaction of betanin and indicaxanthin with human myeloperoxidase and hypochlorous acid. (2005). https://pubmed.ncbi.nlm.nih.gov/15913556/ DOI: 10.1016/j.bbrc.2005.05.031

dose

Betalains 5-80 micromolar

duration

Not specified in accessed primary abstract

evidence_access

Primary PubMed abstract; detailed exposure for PMID 23931157 additionally checked in publisher results. No uninspected full text is claimed.

evidence_scope

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

experimental_model

Human Caco-2 intestinal epithelial cell model

limitations

Low apparent permeability in cultured cells is not a measured human oral bioavailability fraction; findings depend on pigment and assay. The range spans the three compounds; it is not an assigned compound-specific coefficient.

nutrient_topic

Betalains collection; each molecular form, species, exposure and preparation remains explicit. · Betalains

organism

Human Caco-2 intestinal epithelial cell model

plain_language

Indicaxanthin showed low apparent permeability across Caco-2 monolayers; the reported three-pigment range was 4.2-8.9 x 10^-7 cm/s.

primary_references

Uptake and Immunomodulatory Properties of Betanin, Vulgaxanthin I and Indicaxanthin towards Caco-2 Intestinal Cells. (2022). https://pubmed.ncbi.nlm.nih.gov/36009345/ DOI: 10.3390/antiox11081627

route

In vitro exposure

tissue

Intestinal cells and monolayer transport

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 377–385

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Human Caco-2 intestinal epithelial cell model · source_derived_draft · unverified_draft

## betalains-indicaxanthin-transport Indicaxanthin showed low apparent permeability across Caco-2 monolayers; the reported three-pigment range was 4.2-8.9 x 10^-7 cm/s. Model/species: Human Caco-2 intestinal epithelial cell model Tissue: Intestinal cells and monolayer transport Exposure: Betalains 5-80 micromolar Route: In vitro exposure Duration: Not specified in accessed primary abstract Limits: Low apparent permeability in cultured cells is not a measured human oral bioavailability fraction; findings depend on pigment and assay. The range spans the three compounds; it is not an assigned compound-specific coefficient. Primary reference: Uptake and Immunomodulatory Properties of Betanin, Vulgaxanthin I and Indicaxanthin towards Caco-2 Intestinal Cells. (2022). https://pubmed.ncbi.nlm.nih.gov/36009345/ DOI: 10.3390/antiox11081627

dose

25-100 micromolar pigment added to plasma; copper-triggered LDL oxidation

duration

Kinetic oxidation assay; incubation duration not specified in accessed abstract

evidence_access

Primary PubMed abstract; detailed exposure for PMID 23931157 additionally checked in publisher results. No uninspected full text is claimed.

evidence_scope

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

experimental_model

Human pooled plasma from 10 healthy donors; isolated LDL

limitations

Plasma spiking exceeds typical dietary parent-pigment exposure; vitamin synergy refers only to this assay. The authors infer assay synergy; direct tocopheroxyl-radical recycling is not established.

nutrient_topic

Betalains collection; each molecular form, species, exposure and preparation remains explicit. · Betalains

organism

Human pooled plasma from 10 healthy donors; isolated LDL

plain_language

Indicaxanthin preserved LDL vitamin E early during oxidation; combined action protected LDL more than sequential separate action.

primary_references

Increased resistance to oxidation of betalain-enriched human low density lipoproteins. (2003). https://pubmed.ncbi.nlm.nih.gov/12868496/ DOI: 10.1080/1071576031000097490

route

Ex vivo spiking, not oral dosing

tissue

Plasma and LDL

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 87–95

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Human pooled plasma from 10 healthy donors; isolated LDL · source_derived_draft · unverified_draft

## betalains-indicaxanthin-vitamin-e Indicaxanthin preserved LDL vitamin E early during oxidation; combined action protected LDL more than sequential separate action. Model/species: Human pooled plasma from 10 healthy donors; isolated LDL Tissue: Plasma and LDL Exposure: 25-100 micromolar pigment added to plasma; copper-triggered LDL oxidation Route: Ex vivo spiking, not oral dosing Duration: Kinetic oxidation assay; incubation duration not specified in accessed abstract Limits: Plasma spiking exceeds typical dietary parent-pigment exposure; vitamin synergy refers only to this assay. The authors infer assay synergy; direct tocopheroxyl-radical recycling is not established. Primary reference: Increased resistance to oxidation of betalain-enriched human low density lipoproteins. (2003). https://pubmed.ncbi.nlm.nih.gov/12868496/ DOI: 10.1080/1071576031000097490

dose

Indicaxanthin 1-5 micromolar; aqueous cigarette smoke extract

duration

3 h

evidence_access

Primary PubMed abstract; detailed exposure for PMID 23931157 additionally checked in publisher results. No uninspected full text is claimed.

evidence_scope

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

experimental_model

Human isolated red blood cells challenged with cigarette smoke extract

limitations

An isolated-cell smoke-extract experiment does not establish protection against smoking-related disease; no direct Fas-binding assay was reported in the abstract.

nutrient_topic

Betalains collection; each molecular form, species, exposure and preparation remains explicit. · Betalains

organism

Human isolated red blood cells challenged with cigarette smoke extract

plain_language

Indicaxanthin reduced ATP depletion during smoke-extract exposure of isolated red cells.

primary_references

Indicaxanthin prevents eryptosis induced by cigarette smoke extract by interfering with active Fas-mediated signaling. (2024). https://pubmed.ncbi.nlm.nih.gov/38520710/ DOI: 10.1002/biof.2051

route

Ex vivo co-incubation

tissue

Erythrocyte membrane and cytosol

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 477–485

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Human isolated red blood cells challenged with cigarette smoke extract · source_derived_draft · unverified_draft

## betalains-redcell-atp Indicaxanthin reduced ATP depletion during smoke-extract exposure of isolated red cells. Model/species: Human isolated red blood cells challenged with cigarette smoke extract Tissue: Erythrocyte membrane and cytosol Exposure: Indicaxanthin 1-5 micromolar; aqueous cigarette smoke extract Route: Ex vivo co-incubation Duration: 3 h Limits: An isolated-cell smoke-extract experiment does not establish protection against smoking-related disease; no direct Fas-binding assay was reported in the abstract. Primary reference: Indicaxanthin prevents eryptosis induced by cigarette smoke extract by interfering with active Fas-mediated signaling. (2024). https://pubmed.ncbi.nlm.nih.gov/38520710/ DOI: 10.1002/biof.2051

dose

Indicaxanthin 1-5 micromolar; aqueous cigarette smoke extract

duration

3 h

evidence_access

Primary PubMed abstract; detailed exposure for PMID 23931157 additionally checked in publisher results. No uninspected full text is claimed.

evidence_scope

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

experimental_model

Human isolated red blood cells challenged with cigarette smoke extract

limitations

An isolated-cell smoke-extract experiment does not establish protection against smoking-related disease; no direct Fas-binding assay was reported in the abstract.

nutrient_topic

Betalains collection; each molecular form, species, exposure and preparation remains explicit. · Betalains

organism

Human isolated red blood cells challenged with cigarette smoke extract

plain_language

Indicaxanthin reduced smoke-extract-induced caspase-3 cleavage and activity in red cells.

primary_references

Indicaxanthin prevents eryptosis induced by cigarette smoke extract by interfering with active Fas-mediated signaling. (2024). https://pubmed.ncbi.nlm.nih.gov/38520710/ DOI: 10.1002/biof.2051

route

Ex vivo co-incubation

tissue

Erythrocyte membrane and cytosol

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 467–475

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Human isolated red blood cells challenged with cigarette smoke extract · source_derived_draft · unverified_draft

## betalains-redcell-casp3 Indicaxanthin reduced smoke-extract-induced caspase-3 cleavage and activity in red cells. Model/species: Human isolated red blood cells challenged with cigarette smoke extract Tissue: Erythrocyte membrane and cytosol Exposure: Indicaxanthin 1-5 micromolar; aqueous cigarette smoke extract Route: Ex vivo co-incubation Duration: 3 h Limits: An isolated-cell smoke-extract experiment does not establish protection against smoking-related disease; no direct Fas-binding assay was reported in the abstract. Primary reference: Indicaxanthin prevents eryptosis induced by cigarette smoke extract by interfering with active Fas-mediated signaling. (2024). https://pubmed.ncbi.nlm.nih.gov/38520710/ DOI: 10.1002/biof.2051

dose

Indicaxanthin 1-5 micromolar; aqueous cigarette smoke extract

duration

3 h

evidence_access

Primary PubMed abstract; detailed exposure for PMID 23931157 additionally checked in publisher results. No uninspected full text is claimed.

evidence_scope

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

experimental_model

Human isolated red blood cells challenged with cigarette smoke extract

limitations

An isolated-cell smoke-extract experiment does not establish protection against smoking-related disease; no direct Fas-binding assay was reported in the abstract.

nutrient_topic

Betalains collection; each molecular form, species, exposure and preparation remains explicit. · Betalains

organism

Human isolated red blood cells challenged with cigarette smoke extract

plain_language

Indicaxanthin prevented smoke-extract-triggered Fas aggregation and recruitment of FADD and caspase-8 at erythrocyte membranes.

primary_references

Indicaxanthin prevents eryptosis induced by cigarette smoke extract by interfering with active Fas-mediated signaling. (2024). https://pubmed.ncbi.nlm.nih.gov/38520710/ DOI: 10.1002/biof.2051

route

Ex vivo co-incubation

tissue

Erythrocyte membrane and cytosol

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 457–465

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Human isolated red blood cells challenged with cigarette smoke extract · source_derived_draft · unverified_draft

## betalains-redcell-disc Indicaxanthin prevented smoke-extract-triggered Fas aggregation and recruitment of FADD and caspase-8 at erythrocyte membranes. Model/species: Human isolated red blood cells challenged with cigarette smoke extract Tissue: Erythrocyte membrane and cytosol Exposure: Indicaxanthin 1-5 micromolar; aqueous cigarette smoke extract Route: Ex vivo co-incubation Duration: 3 h Limits: An isolated-cell smoke-extract experiment does not establish protection against smoking-related disease; no direct Fas-binding assay was reported in the abstract. Primary reference: Indicaxanthin prevents eryptosis induced by cigarette smoke extract by interfering with active Fas-mediated signaling. (2024). https://pubmed.ncbi.nlm.nih.gov/38520710/ DOI: 10.1002/biof.2051

dose

Indicaxanthin 1-5 micromolar; aqueous cigarette smoke extract

duration

3 h

evidence_access

Primary PubMed abstract; detailed exposure for PMID 23931157 additionally checked in publisher results. No uninspected full text is claimed.

evidence_scope

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

experimental_model

Human isolated red blood cells challenged with cigarette smoke extract

limitations

An isolated-cell smoke-extract experiment does not establish protection against smoking-related disease; no direct Fas-binding assay was reported in the abstract.

nutrient_topic

Betalains collection; each molecular form, species, exposure and preparation remains explicit. · Betalains

organism

Human isolated red blood cells challenged with cigarette smoke extract

plain_language

Indicaxanthin reduced smoke-extract-induced phosphatidylserine externalization.

primary_references

Indicaxanthin prevents eryptosis induced by cigarette smoke extract by interfering with active Fas-mediated signaling. (2024). https://pubmed.ncbi.nlm.nih.gov/38520710/ DOI: 10.1002/biof.2051

route

Ex vivo co-incubation

tissue

Erythrocyte membrane and cytosol

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 487–495

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Human isolated red blood cells challenged with cigarette smoke extract · source_derived_draft · unverified_draft

## betalains-redcell-ps Indicaxanthin reduced smoke-extract-induced phosphatidylserine externalization. Model/species: Human isolated red blood cells challenged with cigarette smoke extract Tissue: Erythrocyte membrane and cytosol Exposure: Indicaxanthin 1-5 micromolar; aqueous cigarette smoke extract Route: Ex vivo co-incubation Duration: 3 h Limits: An isolated-cell smoke-extract experiment does not establish protection against smoking-related disease; no direct Fas-binding assay was reported in the abstract. Primary reference: Indicaxanthin prevents eryptosis induced by cigarette smoke extract by interfering with active Fas-mediated signaling. (2024). https://pubmed.ncbi.nlm.nih.gov/38520710/ DOI: 10.1002/biof.2051

dose

Indicaxanthin 2.5 micromolar; 7-ketocholesterol challenge concentration not specified in accessed abstract

duration

Kinetic observations within 24 h

evidence_access

Primary PubMed abstract; detailed exposure for PMID 23931157 additionally checked in publisher results. No uninspected full text is claimed.

evidence_scope

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

experimental_model

Human THP-1 monocyte/macrophage cells challenged with 7-ketocholesterol

limitations

Calcium preservation is not calcium chelation, dietary calcium depletion or proof of a specific calcium-channel target; clinical plaque regression was not tested.

nutrient_topic

Betalains collection; each molecular form, species, exposure and preparation remains explicit. · Betalains

organism

Human THP-1 monocyte/macrophage cells challenged with 7-ketocholesterol

plain_language

Co-incubating 2.5 micromolar indicaxanthin prevented the measured 7-ketocholesterol-induced pro-apoptotic events.

primary_references

Phytochemical indicaxanthin suppresses 7-ketocholesterol-induced THP-1 cell apoptosis by preventing cytosolic Ca(2+) increase and oxidative stress. (2013). https://pubmed.ncbi.nlm.nih.gov/23228674/ DOI: 10.1017/S000711451200493X

route

In vitro co-incubation

tissue

Myeloid cells; cytosol and mitochondria

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 347–355

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Human THP-1 monocyte/macrophage cells challenged with 7-ketocholesterol · source_derived_draft · unverified_draft

## betalains-thp1-apoptosis Co-incubating 2.5 micromolar indicaxanthin prevented the measured 7-ketocholesterol-induced pro-apoptotic events. Model/species: Human THP-1 monocyte/macrophage cells challenged with 7-ketocholesterol Tissue: Myeloid cells; cytosol and mitochondria Exposure: Indicaxanthin 2.5 micromolar; 7-ketocholesterol challenge concentration not specified in accessed abstract Route: In vitro co-incubation Duration: Kinetic observations within 24 h Limits: Calcium preservation is not calcium chelation, dietary calcium depletion or proof of a specific calcium-channel target; clinical plaque regression was not tested. Primary reference: Phytochemical indicaxanthin suppresses 7-ketocholesterol-induced THP-1 cell apoptosis by preventing cytosolic Ca(2+) increase and oxidative stress. (2013). https://pubmed.ncbi.nlm.nih.gov/23228674/ DOI: 10.1017/S000711451200493X

dose

Indicaxanthin 2.5 micromolar; 7-ketocholesterol challenge concentration not specified in accessed abstract

duration

Kinetic observations within 24 h

evidence_access

Primary PubMed abstract; detailed exposure for PMID 23931157 additionally checked in publisher results. No uninspected full text is claimed.

evidence_scope

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

experimental_model

Human THP-1 monocyte/macrophage cells challenged with 7-ketocholesterol

limitations

Calcium preservation is not calcium chelation, dietary calcium depletion or proof of a specific calcium-channel target; clinical plaque regression was not tested.

nutrient_topic

Betalains collection; each molecular form, species, exposure and preparation remains explicit. · Betalains

organism

Human THP-1 monocyte/macrophage cells challenged with 7-ketocholesterol

plain_language

Indicaxanthin preserved cytosolic calcium homeostasis during the 7-ketocholesterol challenge.

primary_references

Phytochemical indicaxanthin suppresses 7-ketocholesterol-induced THP-1 cell apoptosis by preventing cytosolic Ca(2+) increase and oxidative stress. (2013). https://pubmed.ncbi.nlm.nih.gov/23228674/ DOI: 10.1017/S000711451200493X

route

In vitro co-incubation

tissue

Myeloid cells; cytosol and mitochondria

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 337–345

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Human THP-1 monocyte/macrophage cells challenged with 7-ketocholesterol · source_derived_draft · unverified_draft

## betalains-thp1-calcium Indicaxanthin preserved cytosolic calcium homeostasis during the 7-ketocholesterol challenge. Model/species: Human THP-1 monocyte/macrophage cells challenged with 7-ketocholesterol Tissue: Myeloid cells; cytosol and mitochondria Exposure: Indicaxanthin 2.5 micromolar; 7-ketocholesterol challenge concentration not specified in accessed abstract Route: In vitro co-incubation Duration: Kinetic observations within 24 h Limits: Calcium preservation is not calcium chelation, dietary calcium depletion or proof of a specific calcium-channel target; clinical plaque regression was not tested. Primary reference: Phytochemical indicaxanthin suppresses 7-ketocholesterol-induced THP-1 cell apoptosis by preventing cytosolic Ca(2+) increase and oxidative stress. (2013). https://pubmed.ncbi.nlm.nih.gov/23228674/ DOI: 10.1017/S000711451200493X

dose

Indicaxanthin 2.5 micromolar; 7-ketocholesterol challenge concentration not specified in accessed abstract

duration

Kinetic observations within 24 h

evidence_access

Primary PubMed abstract; detailed exposure for PMID 23931157 additionally checked in publisher results. No uninspected full text is claimed.

evidence_scope

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

experimental_model

Human THP-1 monocyte/macrophage cells challenged with 7-ketocholesterol

limitations

Calcium preservation is not calcium chelation, dietary calcium depletion or proof of a specific calcium-channel target; clinical plaque regression was not tested.

nutrient_topic

Betalains collection; each molecular form, species, exposure and preparation remains explicit. · Betalains

organism

Human THP-1 monocyte/macrophage cells challenged with 7-ketocholesterol

plain_language

Indicaxanthin prevented 7-ketocholesterol-associated NOX4 overexpression in THP-1 cells.

primary_references

Phytochemical indicaxanthin suppresses 7-ketocholesterol-induced THP-1 cell apoptosis by preventing cytosolic Ca(2+) increase and oxidative stress. (2013). https://pubmed.ncbi.nlm.nih.gov/23228674/ DOI: 10.1017/S000711451200493X

route

In vitro co-incubation

tissue

Myeloid cells; cytosol and mitochondria

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 327–335

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Human THP-1 monocyte/macrophage cells challenged with 7-ketocholesterol · source_derived_draft · unverified_draft

## betalains-thp1-nox4 Indicaxanthin prevented 7-ketocholesterol-associated NOX4 overexpression in THP-1 cells. Model/species: Human THP-1 monocyte/macrophage cells challenged with 7-ketocholesterol Tissue: Myeloid cells; cytosol and mitochondria Exposure: Indicaxanthin 2.5 micromolar; 7-ketocholesterol challenge concentration not specified in accessed abstract Route: In vitro co-incubation Duration: Kinetic observations within 24 h Limits: Calcium preservation is not calcium chelation, dietary calcium depletion or proof of a specific calcium-channel target; clinical plaque regression was not tested. Primary reference: Phytochemical indicaxanthin suppresses 7-ketocholesterol-induced THP-1 cell apoptosis by preventing cytosolic Ca(2+) increase and oxidative stress. (2013). https://pubmed.ncbi.nlm.nih.gov/23228674/ DOI: 10.1017/S000711451200493X

availability_state

machinery_impairment Imported condition classification; unverified.

dose

Indicaxanthin 50-100 micromolar; DPI 1 micromolar; LPS 1 microgram/mL

duration

Indicaxanthin 1 h before LPS; PGD2 at 8 h

evidence_access

Primary open full text, relevant results/methods and PubMed metadata.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

LPS-stimulated mouse RAW 264.7 macrophages with DPI exposure

limitations

DPI is not NOX-isoform-selective; pharmacological sensitivity does not establish NOX2 necessity or a nutrient deficiency.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

LPS-stimulated mouse RAW 264.7 macrophages with DPI exposure

plain_language

Adding DPI prevented the indicaxanthin-associated increase in PGD2 production in LPS-stimulated mouse macrophages.

primary_references

Pro-oxidant activity of indicaxanthin from Opuntia ficus indica modulates arachidonate metabolism and prostaglandin synthesis through lipid peroxide production in LPS-stimulated RAW 264.7 macrophages. (2014). https://pubmed.ncbi.nlm.nih.gov/25180166/ DOI: 10.1016/j.redox.2014.07.004

route

In vitro co-incubation

tissue

Redox-dependent prostaglandin pathway

trigger_kind

machinery_impairment Imported condition classification; unverified.

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 184–193

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · LPS-stimulated mouse RAW 264.7 macrophages with DPI exposure · source_derived_draft · unverified_draft

## indicaxanthin-dpi-pgd2-blockade Adding DPI prevented the indicaxanthin-associated increase in PGD2 production in LPS-stimulated mouse macrophages. Model/species: LPS-stimulated mouse RAW 264.7 macrophages with DPI exposure Tissue: Redox-dependent prostaglandin pathway Exposure: Indicaxanthin 50-100 micromolar; DPI 1 micromolar; LPS 1 microgram/mL Route: In vitro co-incubation Duration: Indicaxanthin 1 h before LPS; PGD2 at 8 h Limits: DPI is not NOX-isoform-selective; pharmacological sensitivity does not establish NOX2 necessity or a nutrient deficiency. Primary reference: Pro-oxidant activity of indicaxanthin from Opuntia ficus indica modulates arachidonate metabolism and prostaglandin synthesis through lipid peroxide production in LPS-stimulated RAW 264.7 macrophages. (2014). https://pubmed.ncbi.nlm.nih.gov/25180166/ DOI: 10.1016/j.redox.2014.07.004 Access: Primary open full text, relevant results/methods and PubMed metadata.

dose

400 g yellow cactus pear

duration

Baseline and 90 min after consumption

evidence_access

Primary open full text, relevant results/methods and PubMed metadata.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Six healthy participants in exploratory imaging subgroup

limitations

Small imaging subgroup; a null imaging comparison does not exclude every neural effect. Whole-fruit exposure does not isolate indicaxanthin.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Six healthy participants in exploratory imaging subgroup

plain_language

The six-person imaging subgroup showed no significant resting-state connectivity change after the fruit meal.

primary_references

Modulation of Human Motor Cortical Excitability and Plasticity by Opuntia Ficus Indica Fruit Consumption: Evidence from a Preliminary Study through Non-Invasive Brain Stimulation. (2022). https://pubmed.ncbi.nlm.nih.gov/36432601/ DOI: 10.3390/nu14224915

route

Oral whole fruit

tissue

Resting-state brain networks

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 272–281

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Six healthy participants in exploratory imaging subgroup · source_derived_draft · unverified_draft

## indicaxanthin-human-fruit-fmri-null The six-person imaging subgroup showed no significant resting-state connectivity change after the fruit meal. Model/species: Six healthy participants in exploratory imaging subgroup Tissue: Resting-state brain networks Exposure: 400 g yellow cactus pear Route: Oral whole fruit Duration: Baseline and 90 min after consumption Limits: Small imaging subgroup; a null imaging comparison does not exclude every neural effect. Whole-fruit exposure does not isolate indicaxanthin. Primary reference: Modulation of Human Motor Cortical Excitability and Plasticity by Opuntia Ficus Indica Fruit Consumption: Evidence from a Preliminary Study through Non-Invasive Brain Stimulation. (2022). https://pubmed.ncbi.nlm.nih.gov/36432601/ DOI: 10.3390/nu14224915 Access: Primary open full text, relevant results/methods and PubMed metadata.

dose

400 g yellow cactus pear fruit versus white-fruit comparator; exact indicaxanthin amount unresolved

duration

90 min after fruit; sessions separated by at least one week

evidence_access

Primary open full text, relevant results/methods and PubMed metadata.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Small healthy-male neurostimulation study

limitations

Whole-food single-blind preliminary study. Methods report 12 fruit/8 comparator participants and four comparator exclusions; participant accounting and fruit-color wording have inconsistencies. No isolated-compound efficacy or cognitive benefit was demonstrated.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Small healthy-male neurostimulation study

plain_language

Yellow-cactus-pear consumption was associated with increased motor-cortex intracortical facilitation in the preliminary human study.

primary_references

Modulation of Human Motor Cortical Excitability and Plasticity by Opuntia Ficus Indica Fruit Consumption: Evidence from a Preliminary Study through Non-Invasive Brain Stimulation. (2022). https://pubmed.ncbi.nlm.nih.gov/36432601/ DOI: 10.3390/nu14224915

route

Oral whole fruit

tissue

Primary motor cortex

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 261–270

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Small healthy-male neurostimulation study · source_derived_draft · unverified_draft

## indicaxanthin-human-fruit-icf Yellow-cactus-pear consumption was associated with increased motor-cortex intracortical facilitation in the preliminary human study. Model/species: Small healthy-male neurostimulation study Tissue: Primary motor cortex Exposure: 400 g yellow cactus pear fruit versus white-fruit comparator; exact indicaxanthin amount unresolved Route: Oral whole fruit Duration: 90 min after fruit; sessions separated by at least one week Limits: Whole-food single-blind preliminary study. Methods report 12 fruit/8 comparator participants and four comparator exclusions; participant accounting and fruit-color wording have inconsistencies. No isolated-compound efficacy or cognitive benefit was demonstrated. Primary reference: Modulation of Human Motor Cortical Excitability and Plasticity by Opuntia Ficus Indica Fruit Consumption: Evidence from a Preliminary Study through Non-Invasive Brain Stimulation. (2022). https://pubmed.ncbi.nlm.nih.gov/36432601/ DOI: 10.3390/nu14224915 Access: Primary open full text, relevant results/methods and PubMed metadata.

dose

N-acetylcysteine 2 mM before indicaxanthin 60 micromolar plus cisplatin 10 micromolar

duration

NAC 1 h before the 24 h combination exposure

evidence_access

Primary open full text, relevant results/methods and PubMed metadata.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human HeLa cervical cancer cells with NAC pretreatment

limitations

NAC blunted the combination response without restoring every outcome to baseline. This experiment is not a recommendation for or against NAC during chemotherapy.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Human HeLa cervical cancer cells with NAC pretreatment

plain_language

N-acetylcysteine pretreatment reduced apoptosis caused by the indicaxanthin/cisplatin combination in HeLa cells.

primary_references

The Phytochemical Indicaxanthin Synergistically Enhances Cisplatin-Induced Apoptosis in HeLa Cells via Oxidative Stress-Dependent p53/p21waf1 Axis. (2020). https://pubmed.ncbi.nlm.nih.gov/32630700/ DOI: 10.3390/biom10070994

route

In vitro pretreatment/co-treatment

tissue

Cell death and redox assays

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 327–336

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Human HeLa cervical cancer cells with NAC pretreatment · source_derived_draft · unverified_draft

## indicaxanthin-nac-combination-antagonism N-acetylcysteine pretreatment reduced apoptosis caused by the indicaxanthin/cisplatin combination in HeLa cells. Model/species: Human HeLa cervical cancer cells with NAC pretreatment Tissue: Cell death and redox assays Exposure: N-acetylcysteine 2 mM before indicaxanthin 60 micromolar plus cisplatin 10 micromolar Route: In vitro pretreatment/co-treatment Duration: NAC 1 h before the 24 h combination exposure Limits: NAC blunted the combination response without restoring every outcome to baseline. This experiment is not a recommendation for or against NAC during chemotherapy. Primary reference: The Phytochemical Indicaxanthin Synergistically Enhances Cisplatin-Induced Apoptosis in HeLa Cells via Oxidative Stress-Dependent p53/p21waf1 Axis. (2020). https://pubmed.ncbi.nlm.nih.gov/32630700/ DOI: 10.3390/biom10070994 Access: Primary open full text, relevant results/methods and PubMed metadata.

dose

Indicaxanthin 50-100 micromolar; alpha-tocopherol 100 micromolar; LPS 1 microgram/mL

duration

Indicaxanthin 1 h before LPS; lipid peroxides at 0.5 h, PGD2 at 8 h

evidence_access

Primary open full text, relevant results/methods and PubMed metadata.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

LPS-stimulated mouse RAW 264.7 macrophages

limitations

Experimental vitamin E antagonism of this response is not evidence that vitamin E intake is harmful or that avoiding supplementation improves clinical outcomes.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

LPS-stimulated mouse RAW 264.7 macrophages

plain_language

Co-incubated alpha-tocopherol prevented the indicaxanthin-associated increase in PGD2 production in stimulated mouse macrophages.

primary_references

Pro-oxidant activity of indicaxanthin from Opuntia ficus indica modulates arachidonate metabolism and prostaglandin synthesis through lipid peroxide production in LPS-stimulated RAW 264.7 macrophages. (2014). https://pubmed.ncbi.nlm.nih.gov/25180166/ DOI: 10.1016/j.redox.2014.07.004

route

In vitro co-incubation

tissue

Membrane lipid oxidation and PGD2 production

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 173–182

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · LPS-stimulated mouse RAW 264.7 macrophages · source_derived_draft · unverified_draft

## indicaxanthin-vitamin-e-pgd2-antagonism Co-incubated alpha-tocopherol prevented the indicaxanthin-associated increase in PGD2 production in stimulated mouse macrophages. Model/species: LPS-stimulated mouse RAW 264.7 macrophages Tissue: Membrane lipid oxidation and PGD2 production Exposure: Indicaxanthin 50-100 micromolar; alpha-tocopherol 100 micromolar; LPS 1 microgram/mL Route: In vitro co-incubation Duration: Indicaxanthin 1 h before LPS; lipid peroxides at 0.5 h, PGD2 at 8 h Limits: Experimental vitamin E antagonism of this response is not evidence that vitamin E intake is harmful or that avoiding supplementation improves clinical outcomes. Primary reference: Pro-oxidant activity of indicaxanthin from Opuntia ficus indica modulates arachidonate metabolism and prostaglandin synthesis through lipid peroxide production in LPS-stimulated RAW 264.7 macrophages. (2014). https://pubmed.ncbi.nlm.nih.gov/25180166/ DOI: 10.1016/j.redox.2014.07.004 Access: Primary open full text, relevant results/methods and PubMed metadata.

dose

Single 500 g cactus pear pulp meal: 28 mg indicaxanthin and 16 mg betanin

duration

Plasma/urine followed for 12 h

evidence_access

Primary PubMed abstract; detailed exposure for PMID 23931157 additionally checked in publisher results. No uninspected full text is claimed.

evidence_scope

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

experimental_model

Eight healthy human volunteers

limitations

Whole-food exposure cannot attribute the LDL response exclusively to either pigment; urinary recovery is not absolute absorption.

nutrient_topic

Betalains collection; each molecular form, species, exposure and preparation remains explicit. · Betalains

organism

Eight healthy human volunteers

plain_language

LDL isolated 3 and 5 h after cactus pear ingestion resisted ex vivo oxidation more strongly; LDL vitamin E and beta-carotene levels were unchanged.

primary_references

Absorption, excretion, and distribution of dietary antioxidant betalains in LDLs: potential health effects of betalains in humans. (2004). https://pubmed.ncbi.nlm.nih.gov/15447903/ DOI: 10.1093/ajcn/80.4.941

route

Oral whole food

tissue

Plasma, urine and isolated LDL

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 517–525

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Eight healthy human volunteers · source_derived_draft · unverified_draft

## betalains-human-food-ldl LDL isolated 3 and 5 h after cactus pear ingestion resisted ex vivo oxidation more strongly; LDL vitamin E and beta-carotene levels were unchanged. Model/species: Eight healthy human volunteers Tissue: Plasma, urine and isolated LDL Exposure: Single 500 g cactus pear pulp meal: 28 mg indicaxanthin and 16 mg betanin Route: Oral whole food Duration: Plasma/urine followed for 12 h Limits: Whole-food exposure cannot attribute the LDL response exclusively to either pigment; urinary recovery is not absolute absorption. Primary reference: Absorption, excretion, and distribution of dietary antioxidant betalains in LDLs: potential health effects of betalains in humans. (2004). https://pubmed.ncbi.nlm.nih.gov/15447903/ DOI: 10.1093/ajcn/80.4.941

dose

Single 500 g cactus pear pulp meal: 28 mg indicaxanthin and 16 mg betanin

duration

Plasma/urine followed for 12 h

evidence_access

Primary PubMed abstract; detailed exposure for PMID 23931157 additionally checked in publisher results. No uninspected full text is claimed.

evidence_scope

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

experimental_model

Eight healthy human volunteers

limitations

Whole-food exposure cannot attribute the LDL response exclusively to either pigment; urinary recovery is not absolute absorption.

nutrient_topic

Betalains collection; each molecular form, species, exposure and preparation remains explicit. · Betalains

organism

Eight healthy human volunteers

plain_language

After cactus pear ingestion, plasma indicaxanthin peaked at 3 h and was undetectable by 12 h.

primary_references

Absorption, excretion, and distribution of dietary antioxidant betalains in LDLs: potential health effects of betalains in humans. (2004). https://pubmed.ncbi.nlm.nih.gov/15447903/ DOI: 10.1093/ajcn/80.4.941

route

Oral whole food

tissue

Plasma, urine and isolated LDL

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 507–515

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Eight healthy human volunteers · source_derived_draft · unverified_draft

## betalains-indicaxanthin-human-pk After cactus pear ingestion, plasma indicaxanthin peaked at 3 h and was undetectable by 12 h. Model/species: Eight healthy human volunteers Tissue: Plasma, urine and isolated LDL Exposure: Single 500 g cactus pear pulp meal: 28 mg indicaxanthin and 16 mg betanin Route: Oral whole food Duration: Plasma/urine followed for 12 h Limits: Whole-food exposure cannot attribute the LDL response exclusively to either pigment; urinary recovery is not absolute absorption. Primary reference: Absorption, excretion, and distribution of dietary antioxidant betalains in LDLs: potential health effects of betalains in humans. (2004). https://pubmed.ncbi.nlm.nih.gov/15447903/ DOI: 10.1093/ajcn/80.4.941