Human pregnane X receptor / SXR / PXR / NR1I2

evidence_span

{"source_cache": "artifacts/dim-research/25542144.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d", "start_char": 0, "end_char": 1440, "text_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d"}

experimental_model

Promoter reporters, expression, knockdown and transport assays

exposure

DIM exposure with PXR inhibition or knockdown controls

limitations

Cell-model induction, not a quantified human interaction. Older liver-slice assays showed little CYP3A4 response under their conditions.

nutrient_topic

Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM

organism

Human hepatocytes and intestinal cell models

plain_language

The same exposure can change a transporter as well as an enzyme.

primary_references

[dim-p25542144] Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. (2015). https://pubmed.ncbi.nlm.nih.gov/25542144/ DOI: 10.1016/j.toxlet.2014.12.015

tissue_or_cell_type

PXR-regulated CYP3A4 and ABCB1

Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 519–530

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Promoter reporters, expression, knockdown and transport assays · source_derived_draft · unverified_draft

### dim-pxr-abcb1 DIM increased MDR1/ABCB1 expression in a PXR-dependent manner. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same exposure can change a transporter as well as an enzyme. organism: Human hepatocytes and intestinal cell models tissue_or_cell_type: PXR-regulated CYP3A4 and ABCB1 experimental_model: Promoter reporters, expression, knockdown and transport assays limitations: Cell-model induction, not a quantified human interaction. Older liver-slice assays showed little CYP3A4 response under their conditions. exposure: DIM exposure with PXR inhibition or knockdown controls evidence_span: {"source_cache": "artifacts/dim-research/25542144.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d", "start_char": 0, "end_char": 1440, "text_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d"} [dim-p25542144] Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. (2015). https://pubmed.ncbi.nlm.nih.gov/25542144/ DOI: 10.1016/j.toxlet.2014.12.015

evidence_span

{"source_cache": "artifacts/dim-research/25542144.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d", "start_char": 0, "end_char": 1440, "text_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d"}

experimental_model

Promoter reporters, expression, knockdown and transport assays

exposure

DIM exposure with PXR inhibition or knockdown controls

limitations

Cell-model induction, not a quantified human interaction. Older liver-slice assays showed little CYP3A4 response under their conditions.

nutrient_topic

Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM

organism

Human hepatocytes and intestinal cell models

plain_language

CYP3A4 belongs in this map alongside CYP1A2.

primary_references

[dim-p25542144] Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. (2015). https://pubmed.ncbi.nlm.nih.gov/25542144/ DOI: 10.1016/j.toxlet.2014.12.015

tissue_or_cell_type

PXR-regulated CYP3A4 and ABCB1

Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 506–517

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Promoter reporters, expression, knockdown and transport assays · source_derived_draft · unverified_draft

### dim-pxr-cyp3a4 DIM increased CYP3A4 expression in a PXR-dependent manner. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: CYP3A4 belongs in this map alongside CYP1A2. organism: Human hepatocytes and intestinal cell models tissue_or_cell_type: PXR-regulated CYP3A4 and ABCB1 experimental_model: Promoter reporters, expression, knockdown and transport assays limitations: Cell-model induction, not a quantified human interaction. Older liver-slice assays showed little CYP3A4 response under their conditions. exposure: DIM exposure with PXR inhibition or knockdown controls evidence_span: {"source_cache": "artifacts/dim-research/25542144.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d", "start_char": 0, "end_char": 1440, "text_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d"} [dim-p25542144] Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. (2015). https://pubmed.ncbi.nlm.nih.gov/25542144/ DOI: 10.1016/j.toxlet.2014.12.015

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/dim-research/25542144.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d", "start_char": 0, "end_char": 1440, "text_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d"}

experimental_model

Promoter reporters, expression, knockdown and transport assays

exposure

DIM exposure with PXR inhibition or knockdown controls

limitations

Cell-model induction, not a quantified human interaction. Older liver-slice assays showed little CYP3A4 response under their conditions.

nutrient_topic

Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM

organism

Human hepatocytes and intestinal cell models

plain_language

The response weakened when a required signaling component was blocked.

primary_references

[dim-p25542144] Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. (2015). https://pubmed.ncbi.nlm.nih.gov/25542144/ DOI: 10.1016/j.toxlet.2014.12.015

tissue_or_cell_type

PXR-regulated CYP3A4 and ABCB1

trigger_kind

machinery_impairment Imported condition classification; unverified.

Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 558–569

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Promoter reporters, expression, knockdown and transport assays · source_derived_draft · unverified_draft

### dim-pxr-loss-abcb1 PXR knockdown or inhibition attenuated DIM-induced ABCB1 expression. Condition category: machinery_impairment nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The response weakened when a required signaling component was blocked. organism: Human hepatocytes and intestinal cell models tissue_or_cell_type: PXR-regulated CYP3A4 and ABCB1 experimental_model: Promoter reporters, expression, knockdown and transport assays limitations: Cell-model induction, not a quantified human interaction. Older liver-slice assays showed little CYP3A4 response under their conditions. exposure: DIM exposure with PXR inhibition or knockdown controls evidence_span: {"source_cache": "artifacts/dim-research/25542144.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d", "start_char": 0, "end_char": 1440, "text_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d"} [dim-p25542144] Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. (2015). https://pubmed.ncbi.nlm.nih.gov/25542144/ DOI: 10.1016/j.toxlet.2014.12.015

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/dim-research/25542144.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d", "start_char": 0, "end_char": 1440, "text_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d"}

experimental_model

Promoter reporters, expression, knockdown and transport assays

exposure

DIM exposure with PXR inhibition or knockdown controls

limitations

Cell-model induction, not a quantified human interaction. Older liver-slice assays showed little CYP3A4 response under their conditions.

nutrient_topic

Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM

organism

Human hepatocytes and intestinal cell models

plain_language

The response weakened when a required signaling component was blocked.

primary_references

[dim-p25542144] Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. (2015). https://pubmed.ncbi.nlm.nih.gov/25542144/ DOI: 10.1016/j.toxlet.2014.12.015

tissue_or_cell_type

PXR-regulated CYP3A4 and ABCB1

trigger_kind

machinery_impairment Imported condition classification; unverified.

Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 545–556

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Promoter reporters, expression, knockdown and transport assays · source_derived_draft · unverified_draft

### dim-pxr-loss-cyp3a4 PXR knockdown or inhibition attenuated DIM-induced CYP3A4 expression. Condition category: machinery_impairment nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The response weakened when a required signaling component was blocked. organism: Human hepatocytes and intestinal cell models tissue_or_cell_type: PXR-regulated CYP3A4 and ABCB1 experimental_model: Promoter reporters, expression, knockdown and transport assays limitations: Cell-model induction, not a quantified human interaction. Older liver-slice assays showed little CYP3A4 response under their conditions. exposure: DIM exposure with PXR inhibition or knockdown controls evidence_span: {"source_cache": "artifacts/dim-research/25542144.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d", "start_char": 0, "end_char": 1440, "text_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d"} [dim-p25542144] Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. (2015). https://pubmed.ncbi.nlm.nih.gov/25542144/ DOI: 10.1016/j.toxlet.2014.12.015

evidence_span

{"source_cache": "artifacts/k2-research/16606623.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a2c0e756d507fd0cef9dea48e3eedc193084378509ec54bce2c097f8491e4b45", "start_char": 0, "end_char": 1266, "text_sha256": "a2c0e756d507fd0cef9dea48e3eedc193084378509ec54bce2c097f8491e4b45"}

experimental_model

Microarray, qPCR and gain/loss-of-function studies

exposure

Vitamin K2 and rifampicin/SXR stimulation

limitations

Cell transcription and collagen accumulation; not a human fracture study.

nutrient_topic

Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family

organism

Human osteoblastic MG63 cells

plain_language

The receptor connects to a separately identifiable downstream gene.

primary_references

[k2-p16606623] Steroid and xenobiotic receptor SXR mediates vitamin K2-activated transcription of extracellular matrix-related genes and collagen accumulation in osteoblastic cells. (2006). https://pubmed.ncbi.nlm.nih.gov/16606623/ DOI: 10.1074/jbc.m600896200

tissue_or_cell_type

Extracellular-matrix gene regulation

Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 747–758

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Microarray, qPCR and gain/loss-of-function studies · source_derived_draft · unverified_draft

### k2-sxr-cd14 CD14 was identified as a primary SXR target responsive to vitamin K2 and rifampicin in osteoblastic cells. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The receptor connects to a separately identifiable downstream gene. organism: Human osteoblastic MG63 cells tissue_or_cell_type: Extracellular-matrix gene regulation experimental_model: Microarray, qPCR and gain/loss-of-function studies limitations: Cell transcription and collagen accumulation; not a human fracture study. exposure: Vitamin K2 and rifampicin/SXR stimulation evidence_span: {"source_cache": "artifacts/k2-research/16606623.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a2c0e756d507fd0cef9dea48e3eedc193084378509ec54bce2c097f8491e4b45", "start_char": 0, "end_char": 1266, "text_sha256": "a2c0e756d507fd0cef9dea48e3eedc193084378509ec54bce2c097f8491e4b45"} [k2-p16606623] Steroid and xenobiotic receptor SXR mediates vitamin K2-activated transcription of extracellular matrix-related genes and collagen accumulation in osteoblastic cells. (2006). https://pubmed.ncbi.nlm.nih.gov/16606623/ DOI: 10.1074/jbc.m600896200

evidence_span

{"source_cache": "artifacts/k2-research/16606623.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a2c0e756d507fd0cef9dea48e3eedc193084378509ec54bce2c097f8491e4b45", "start_char": 0, "end_char": 1266, "text_sha256": "a2c0e756d507fd0cef9dea48e3eedc193084378509ec54bce2c097f8491e4b45"}

experimental_model

Microarray, qPCR and gain/loss-of-function studies

exposure

Vitamin K2 and rifampicin/SXR stimulation

limitations

Cell transcription and collagen accumulation; not a human fracture study.

nutrient_topic

Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family

organism

Human osteoblastic MG63 cells

plain_language

The receptor connects to a separately identifiable downstream gene.

primary_references

[k2-p16606623] Steroid and xenobiotic receptor SXR mediates vitamin K2-activated transcription of extracellular matrix-related genes and collagen accumulation in osteoblastic cells. (2006). https://pubmed.ncbi.nlm.nih.gov/16606623/ DOI: 10.1074/jbc.m600896200

tissue_or_cell_type

Extracellular-matrix gene regulation

Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 734–745

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Microarray, qPCR and gain/loss-of-function studies · source_derived_draft · unverified_draft

### k2-sxr-matn2 MATN2 was identified as a primary SXR target responsive to vitamin K2 and rifampicin in osteoblastic cells. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The receptor connects to a separately identifiable downstream gene. organism: Human osteoblastic MG63 cells tissue_or_cell_type: Extracellular-matrix gene regulation experimental_model: Microarray, qPCR and gain/loss-of-function studies limitations: Cell transcription and collagen accumulation; not a human fracture study. exposure: Vitamin K2 and rifampicin/SXR stimulation evidence_span: {"source_cache": "artifacts/k2-research/16606623.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a2c0e756d507fd0cef9dea48e3eedc193084378509ec54bce2c097f8491e4b45", "start_char": 0, "end_char": 1266, "text_sha256": "a2c0e756d507fd0cef9dea48e3eedc193084378509ec54bce2c097f8491e4b45"} [k2-p16606623] Steroid and xenobiotic receptor SXR mediates vitamin K2-activated transcription of extracellular matrix-related genes and collagen accumulation in osteoblastic cells. (2006). https://pubmed.ncbi.nlm.nih.gov/16606623/ DOI: 10.1074/jbc.m600896200

evidence_span

{"source_cache": "artifacts/k2-research/16606623.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a2c0e756d507fd0cef9dea48e3eedc193084378509ec54bce2c097f8491e4b45", "start_char": 0, "end_char": 1266, "text_sha256": "a2c0e756d507fd0cef9dea48e3eedc193084378509ec54bce2c097f8491e4b45"}

experimental_model

Microarray, qPCR and gain/loss-of-function studies

exposure

Vitamin K2 and rifampicin/SXR stimulation

limitations

Cell transcription and collagen accumulation; not a human fracture study.

nutrient_topic

Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family

organism

Human osteoblastic MG63 cells

plain_language

The receptor connects to a separately identifiable downstream gene.

primary_references

[k2-p16606623] Steroid and xenobiotic receptor SXR mediates vitamin K2-activated transcription of extracellular matrix-related genes and collagen accumulation in osteoblastic cells. (2006). https://pubmed.ncbi.nlm.nih.gov/16606623/ DOI: 10.1074/jbc.m600896200

tissue_or_cell_type

Extracellular-matrix gene regulation

Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 721–732

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Microarray, qPCR and gain/loss-of-function studies · source_derived_draft · unverified_draft

### k2-sxr-tsku TSKU was identified as a primary SXR target responsive to vitamin K2 and rifampicin in osteoblastic cells. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The receptor connects to a separately identifiable downstream gene. organism: Human osteoblastic MG63 cells tissue_or_cell_type: Extracellular-matrix gene regulation experimental_model: Microarray, qPCR and gain/loss-of-function studies limitations: Cell transcription and collagen accumulation; not a human fracture study. exposure: Vitamin K2 and rifampicin/SXR stimulation evidence_span: {"source_cache": "artifacts/k2-research/16606623.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a2c0e756d507fd0cef9dea48e3eedc193084378509ec54bce2c097f8491e4b45", "start_char": 0, "end_char": 1266, "text_sha256": "a2c0e756d507fd0cef9dea48e3eedc193084378509ec54bce2c097f8491e4b45"} [k2-p16606623] Steroid and xenobiotic receptor SXR mediates vitamin K2-activated transcription of extracellular matrix-related genes and collagen accumulation in osteoblastic cells. (2006). https://pubmed.ncbi.nlm.nih.gov/16606623/ DOI: 10.1074/jbc.m600896200

evidence_span

{"source_cache": "artifacts/dim-research/25542144.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d", "start_char": 0, "end_char": 1440, "text_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d"}

experimental_model

Promoter reporters, expression, knockdown and transport assays

exposure

DIM exposure with PXR inhibition or knockdown controls

limitations

Cell-model induction, not a quantified human interaction. Older liver-slice assays showed little CYP3A4 response under their conditions.

nutrient_topic

Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM

organism

Human hepatocytes and intestinal cell models

plain_language

A second receptor connects DIM to another drug-metabolism pathway.

primary_references

[dim-p25542144] Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. (2015). https://pubmed.ncbi.nlm.nih.gov/25542144/ DOI: 10.1016/j.toxlet.2014.12.015

tissue_or_cell_type

PXR-regulated CYP3A4 and ABCB1

Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 493–504

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Promoter reporters, expression, knockdown and transport assays · source_derived_draft · unverified_draft

### dim-pxr-activation DIM activated human PXR-dependent CYP3A4 promoter transcription. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second receptor connects DIM to another drug-metabolism pathway. organism: Human hepatocytes and intestinal cell models tissue_or_cell_type: PXR-regulated CYP3A4 and ABCB1 experimental_model: Promoter reporters, expression, knockdown and transport assays limitations: Cell-model induction, not a quantified human interaction. Older liver-slice assays showed little CYP3A4 response under their conditions. exposure: DIM exposure with PXR inhibition or knockdown controls evidence_span: {"source_cache": "artifacts/dim-research/25542144.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d", "start_char": 0, "end_char": 1440, "text_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d"} [dim-p25542144] Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. (2015). https://pubmed.ncbi.nlm.nih.gov/25542144/ DOI: 10.1016/j.toxlet.2014.12.015

evidence_span

{"source_cache": "artifacts/ceylon-research/39845339.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0bbeb0c733ff258e7efaf517438f4368e29bf3afda37cfbac3be149bde094758", "start_char": 27731, "end_char": 28275, "text_sha256": "a6199e4f39be87d9019845ab113a787a4f41c373e18c9ba8ed0aeaef771aa7c1"}

experimental_model

Human receptor reporters and CYP inhibition assays

exposure

Oil/parent/metabolite comparisons; PXR 0.62–20 micrograms/mL for 24 hours

limitations

Reporter activation is not demonstrated induction of clinical drug clearance. HepG2 is liver-derived; full results distinguish it from intestinal LS174T.

nutrient_topic

Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect. · Ceylon cinnamon / Cinnamomum verum bark preparations

organism

Human-derived reporter cells and human CYP assay systems

plain_language

The metabolite activated a liver-cell reporter at the highest tested concentration.

primary_references

[ceylon-p39845339] Evaluation of bioaccessibility, metabolic clearance and interaction with xenobiotic receptors (PXR and AhR) of cinnamaldehyde. (2025). https://pubmed.ncbi.nlm.nih.gov/39845339/ DOI: 10.1016/j.fochms.2024.100237

tissue_or_cell_type

HepG2 hepatocellular carcinoma cells

Ceylon cinnamon: metabolism, signaling and nutrient connections (2026-09-17) · lines 909–920

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human receptor reporters and CYP inhibition assays · source_derived_draft · unverified_draft

### ceylon-acid-pxr-hep Cinnamic acid activated the human PXR reporter in HepG2 cells, exceeding threefold at 20 micrograms/mL. Condition category: normal nutrient_topic: Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect. plain_language: The metabolite activated a liver-cell reporter at the highest tested concentration. organism: Human-derived reporter cells and human CYP assay systems tissue_or_cell_type: HepG2 hepatocellular carcinoma cells experimental_model: Human receptor reporters and CYP inhibition assays limitations: Reporter activation is not demonstrated induction of clinical drug clearance. HepG2 is liver-derived; full results distinguish it from intestinal LS174T. exposure: Oil/parent/metabolite comparisons; PXR 0.62–20 micrograms/mL for 24 hours evidence_span: {"source_cache": "artifacts/ceylon-research/39845339.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0bbeb0c733ff258e7efaf517438f4368e29bf3afda37cfbac3be149bde094758", "start_char": 27731, "end_char": 28275, "text_sha256": "a6199e4f39be87d9019845ab113a787a4f41c373e18c9ba8ed0aeaef771aa7c1"} [ceylon-p39845339] Evaluation of bioaccessibility, metabolic clearance and interaction with xenobiotic receptors (PXR and AhR) of cinnamaldehyde. (2025). https://pubmed.ncbi.nlm.nih.gov/39845339/ DOI: 10.1016/j.fochms.2024.100237

evidence_span

{"source_cache": "artifacts/ceylon-research/39845339.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0bbeb0c733ff258e7efaf517438f4368e29bf3afda37cfbac3be149bde094758", "start_char": 28692, "end_char": 28993, "text_sha256": "069505cad7f859be7641d117d22fde217c5391879239077e55d4919b047a2bfc"}

experimental_model

Human receptor reporters and CYP inhibition assays

exposure

Oil/parent/metabolite comparisons; PXR 0.62–20 micrograms/mL for 24 hours

limitations

Reporter activation is not demonstrated induction of clinical drug clearance. HepG2 is liver-derived; full results distinguish it from intestinal LS174T.

nutrient_topic

Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect. · Ceylon cinnamon / Cinnamomum verum bark preparations

organism

Human-derived reporter cells and human CYP assay systems

plain_language

The metabolite activated the intestinal reporter at the highest tested concentration.

primary_references

[ceylon-p39845339] Evaluation of bioaccessibility, metabolic clearance and interaction with xenobiotic receptors (PXR and AhR) of cinnamaldehyde. (2025). https://pubmed.ncbi.nlm.nih.gov/39845339/ DOI: 10.1016/j.fochms.2024.100237

tissue_or_cell_type

LS174T intestinal carcinoma cells

Ceylon cinnamon: metabolism, signaling and nutrient connections (2026-09-17) · lines 948–959

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human receptor reporters and CYP inhibition assays · source_derived_draft · unverified_draft

### ceylon-acid-pxr-intestine Cinnamic acid activated the human PXR reporter more than threefold in LS174T cells at 20 micrograms/mL; lower concentrations were not significant. Condition category: normal nutrient_topic: Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect. plain_language: The metabolite activated the intestinal reporter at the highest tested concentration. organism: Human-derived reporter cells and human CYP assay systems tissue_or_cell_type: LS174T intestinal carcinoma cells experimental_model: Human receptor reporters and CYP inhibition assays limitations: Reporter activation is not demonstrated induction of clinical drug clearance. HepG2 is liver-derived; full results distinguish it from intestinal LS174T. exposure: Oil/parent/metabolite comparisons; PXR 0.62–20 micrograms/mL for 24 hours evidence_span: {"source_cache": "artifacts/ceylon-research/39845339.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0bbeb0c733ff258e7efaf517438f4368e29bf3afda37cfbac3be149bde094758", "start_char": 28692, "end_char": 28993, "text_sha256": "069505cad7f859be7641d117d22fde217c5391879239077e55d4919b047a2bfc"} [ceylon-p39845339] Evaluation of bioaccessibility, metabolic clearance and interaction with xenobiotic receptors (PXR and AhR) of cinnamaldehyde. (2025). https://pubmed.ncbi.nlm.nih.gov/39845339/ DOI: 10.1016/j.fochms.2024.100237

evidence_span

{"source_cache": "artifacts/ceylon-research/39845339.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0bbeb0c733ff258e7efaf517438f4368e29bf3afda37cfbac3be149bde094758", "start_char": 27731, "end_char": 28275, "text_sha256": "a6199e4f39be87d9019845ab113a787a4f41c373e18c9ba8ed0aeaef771aa7c1"}

experimental_model

Human receptor reporters and CYP inhibition assays

exposure

Oil/parent/metabolite comparisons; PXR 0.62–20 micrograms/mL for 24 hours

limitations

Reporter activation is not demonstrated induction of clinical drug clearance. HepG2 is liver-derived; full results distinguish it from intestinal LS174T.

nutrient_topic

Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect. · Ceylon cinnamon / Cinnamomum verum bark preparations

organism

Human-derived reporter cells and human CYP assay systems

plain_language

This liver-cell result differed from the intestinal-cell result.

primary_references

[ceylon-p39845339] Evaluation of bioaccessibility, metabolic clearance and interaction with xenobiotic receptors (PXR and AhR) of cinnamaldehyde. (2025). https://pubmed.ncbi.nlm.nih.gov/39845339/ DOI: 10.1016/j.fochms.2024.100237

tissue_or_cell_type

HepG2 hepatocellular carcinoma cells

Ceylon cinnamon: metabolism, signaling and nutrient connections (2026-09-17) · lines 922–933

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human receptor reporters and CYP inhibition assays · source_derived_draft · unverified_draft

### ceylon-oil-pxr-hep-null The oil did not activate the PXR reporter in HepG2 cells over the tested range. Condition category: normal nutrient_topic: Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect. plain_language: This liver-cell result differed from the intestinal-cell result. organism: Human-derived reporter cells and human CYP assay systems tissue_or_cell_type: HepG2 hepatocellular carcinoma cells experimental_model: Human receptor reporters and CYP inhibition assays limitations: Reporter activation is not demonstrated induction of clinical drug clearance. HepG2 is liver-derived; full results distinguish it from intestinal LS174T. exposure: Oil/parent/metabolite comparisons; PXR 0.62–20 micrograms/mL for 24 hours evidence_span: {"source_cache": "artifacts/ceylon-research/39845339.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0bbeb0c733ff258e7efaf517438f4368e29bf3afda37cfbac3be149bde094758", "start_char": 27731, "end_char": 28275, "text_sha256": "a6199e4f39be87d9019845ab113a787a4f41c373e18c9ba8ed0aeaef771aa7c1"} [ceylon-p39845339] Evaluation of bioaccessibility, metabolic clearance and interaction with xenobiotic receptors (PXR and AhR) of cinnamaldehyde. (2025). https://pubmed.ncbi.nlm.nih.gov/39845339/ DOI: 10.1016/j.fochms.2024.100237

evidence_span

{"source_cache": "artifacts/ceylon-research/39845339.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0bbeb0c733ff258e7efaf517438f4368e29bf3afda37cfbac3be149bde094758", "start_char": 28692, "end_char": 28993, "text_sha256": "069505cad7f859be7641d117d22fde217c5391879239077e55d4919b047a2bfc"}

experimental_model

Human receptor reporters and CYP inhibition assays

exposure

Oil/parent/metabolite comparisons; PXR 0.62–20 micrograms/mL for 24 hours

limitations

Reporter activation is not demonstrated induction of clinical drug clearance. HepG2 is liver-derived; full results distinguish it from intestinal LS174T.

nutrient_topic

Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect. · Ceylon cinnamon / Cinnamomum verum bark preparations

organism

Human-derived reporter cells and human CYP assay systems

plain_language

A high-concentration intestinal-cell reporter response does not establish a drug interaction in people.

primary_references

[ceylon-p39845339] Evaluation of bioaccessibility, metabolic clearance and interaction with xenobiotic receptors (PXR and AhR) of cinnamaldehyde. (2025). https://pubmed.ncbi.nlm.nih.gov/39845339/ DOI: 10.1016/j.fochms.2024.100237

tissue_or_cell_type

LS174T intestinal carcinoma cells

Ceylon cinnamon: metabolism, signaling and nutrient connections (2026-09-17) · lines 935–946

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human receptor reporters and CYP inhibition assays · source_derived_draft · unverified_draft

### ceylon-oil-pxr-intestine Oil activated the human PXR reporter more than threefold in LS174T cells at 20 micrograms/mL; lower concentrations were not significant. Condition category: normal nutrient_topic: Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect. plain_language: A high-concentration intestinal-cell reporter response does not establish a drug interaction in people. organism: Human-derived reporter cells and human CYP assay systems tissue_or_cell_type: LS174T intestinal carcinoma cells experimental_model: Human receptor reporters and CYP inhibition assays limitations: Reporter activation is not demonstrated induction of clinical drug clearance. HepG2 is liver-derived; full results distinguish it from intestinal LS174T. exposure: Oil/parent/metabolite comparisons; PXR 0.62–20 micrograms/mL for 24 hours evidence_span: {"source_cache": "artifacts/ceylon-research/39845339.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0bbeb0c733ff258e7efaf517438f4368e29bf3afda37cfbac3be149bde094758", "start_char": 28692, "end_char": 28993, "text_sha256": "069505cad7f859be7641d117d22fde217c5391879239077e55d4919b047a2bfc"} [ceylon-p39845339] Evaluation of bioaccessibility, metabolic clearance and interaction with xenobiotic receptors (PXR and AhR) of cinnamaldehyde. (2025). https://pubmed.ncbi.nlm.nih.gov/39845339/ DOI: 10.1016/j.fochms.2024.100237

evidence_span

{"source_cache": "artifacts/k2-research/12920130.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "073faa7585981854cba6f1544fbe593a19b98f2ba6b9aec02c32375171e46617", "start_char": 0, "end_char": 1589, "text_sha256": "073faa7585981854cba6f1544fbe593a19b98f2ba6b9aec02c32375171e46617"}

experimental_model

Ligand binding, gene expression and receptor-null mouse cells

exposure

Vitamin K2 exposure and receptor deficiency

limitations

Preclinical transcription effects; supplement-level target engagement in people is not established. Abstract calls the tested ligand K2 without distinguishing every homologue.

nutrient_topic

Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family

organism

Human osteosarcoma cells and mouse calvarial cells

plain_language

K2 can have a receptor-signaling role separate from protein carboxylation.

primary_references

[k2-p12920130] Vitamin K2 regulation of bone homeostasis is mediated by the steroid and xenobiotic receptor SXR. (2003). https://pubmed.ncbi.nlm.nih.gov/12920130/ DOI: 10.1074/jbc.m303136200

tissue_or_cell_type

SXR/PXR transcription

Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 695–706

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ligand binding, gene expression and receptor-null mouse cells · source_derived_draft · unverified_draft

### k2-k2-sxr Vitamin K2 bound and activated human SXR and induced its CYP3A4 target gene in the tested system. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: K2 can have a receptor-signaling role separate from protein carboxylation. organism: Human osteosarcoma cells and mouse calvarial cells tissue_or_cell_type: SXR/PXR transcription experimental_model: Ligand binding, gene expression and receptor-null mouse cells limitations: Preclinical transcription effects; supplement-level target engagement in people is not established. Abstract calls the tested ligand K2 without distinguishing every homologue. exposure: Vitamin K2 exposure and receptor deficiency evidence_span: {"source_cache": "artifacts/k2-research/12920130.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "073faa7585981854cba6f1544fbe593a19b98f2ba6b9aec02c32375171e46617", "start_char": 0, "end_char": 1589, "text_sha256": "073faa7585981854cba6f1544fbe593a19b98f2ba6b9aec02c32375171e46617"} [k2-p12920130] Vitamin K2 regulation of bone homeostasis is mediated by the steroid and xenobiotic receptor SXR. (2003). https://pubmed.ncbi.nlm.nih.gov/12920130/ DOI: 10.1074/jbc.m303136200

evidence_access

Primary full text, Figure 1

experimental_model

Human PXR reporter in 293T cells.

limitations

Millimolar indole is an assay condition, not a verified systemic human exposure.

nutrient_topic

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

plain_language

A partner microbial metabolite changed the human receptor response.

primary_references

Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and Toll-like receptor 4. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25065623/ · DOI 10.1016/j.immuni.2014.06.014

Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 530–536

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human PXR reporter in 293T cells. · source_derived_draft · unverified_draft

## tryptophan-ipa-human-pxr A partner microbial metabolite changed the human receptor response. Indolepropionate alone weakly activated human PXR, with an EC50 near 120 micromolar; adding 1 mM indole enhanced activation. Model: Human PXR reporter in 293T cells. Limitations: Millimolar indole is an assay condition, not a verified systemic human exposure. Evidence access: Primary full text, Figure 1 Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and Toll-like receptor 4. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25065623/ · DOI 10.1016/j.immuni.2014.06.014