Coumarin

evidence_span

{"source_cache": "artifacts/coumarin-research/9929524.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6d6d4760bdd321dda87f82927c5dfcc7120ed963c101d799473ed53ff4c7764b", "start_char": 0, "end_char": 1579, "text_sha256": "6d6d4760bdd321dda87f82927c5dfcc7120ed963c101d799473ed53ff4c7764b"}

experimental_model

Randomized placebo-controlled crossover replication trial

exposure

Coumarin 200 mg twice daily versus placebo, six months each

limitations

Specific disease population and pharmacological exposure; liver-test incidence cannot be extrapolated to food doses.

nutrient_topic

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

organism

Human

plain_language

The larger trial found no arm-volume benefit.

primary_references

[coumarin-p9929524] Lack of effect of coumarin in women with lymphedema after treatment for breast cancer. (1999). https://pubmed.ncbi.nlm.nih.gov/9929524/ DOI: 10.1056/nejm199902043400503

tissue_or_cell_type

140 women with chronic arm lymphedema after breast cancer treatment

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 761–772

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized placebo-controlled crossover replication trial · source_derived_draft · unverified_draft

### coumarin-arm-null At six months arm volume changed by +58 mL on coumarin versus +21 mL on placebo (P=0.80). Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The larger trial found no arm-volume benefit. organism: Human tissue_or_cell_type: 140 women with chronic arm lymphedema after breast cancer treatment experimental_model: Randomized placebo-controlled crossover replication trial limitations: Specific disease population and pharmacological exposure; liver-test incidence cannot be extrapolated to food doses. exposure: Coumarin 200 mg twice daily versus placebo, six months each evidence_span: {"source_cache": "artifacts/coumarin-research/9929524.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6d6d4760bdd321dda87f82927c5dfcc7120ed963c101d799473ed53ff4c7764b", "start_char": 0, "end_char": 1579, "text_sha256": "6d6d4760bdd321dda87f82927c5dfcc7120ed963c101d799473ed53ff4c7764b"} [coumarin-p9929524] Lack of effect of coumarin in women with lymphedema after treatment for breast cancer. (1999). https://pubmed.ncbi.nlm.nih.gov/9929524/ DOI: 10.1056/nejm199902043400503

evidence_span

{"source_cache": "artifacts/coumarin-research/8377779.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d4b9a301f1334d388b1469a12453ee1af75bcb87f52277dbfac03bcdb045c9ad", "start_char": 0, "end_char": 1907, "text_sha256": "d4b9a301f1334d388b1469a12453ee1af75bcb87f52277dbfac03bcdb045c9ad"}

experimental_model

Randomized double-blind placebo-controlled crossover trial

exposure

Coumarin 400 mg/day and placebo, six months each

limitations

Small older mixed-population trial; positive arm finding was not reproduced in the larger subsequent study.

nutrient_topic

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

organism

Human

plain_language

This small trial reported less arm swelling.

primary_references

[coumarin-p8377779] Treatment of lymphedema of the arms and legs with 5,6-benzo-[alpha]-pyrone. (1993). https://pubmed.ncbi.nlm.nih.gov/8377779/ DOI: 10.1056/nejm199310143291604

tissue_or_cell_type

31 postmastectomy arm and 21 other-cause leg lymphedema patients

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 735–746

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind placebo-controlled crossover trial · source_derived_draft · unverified_draft

### coumarin-arm-positive The 1993 trial reported arm edema declining from 46% to 26% above normal during active treatment (P<0.001). Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This small trial reported less arm swelling. organism: Human tissue_or_cell_type: 31 postmastectomy arm and 21 other-cause leg lymphedema patients experimental_model: Randomized double-blind placebo-controlled crossover trial limitations: Small older mixed-population trial; positive arm finding was not reproduced in the larger subsequent study. exposure: Coumarin 400 mg/day and placebo, six months each evidence_span: {"source_cache": "artifacts/coumarin-research/8377779.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d4b9a301f1334d388b1469a12453ee1af75bcb87f52277dbfac03bcdb045c9ad", "start_char": 0, "end_char": 1907, "text_sha256": "d4b9a301f1334d388b1469a12453ee1af75bcb87f52277dbfac03bcdb045c9ad"} [coumarin-p8377779] Treatment of lymphedema of the arms and legs with 5,6-benzo-[alpha]-pyrone. (1993). https://pubmed.ncbi.nlm.nih.gov/8377779/ DOI: 10.1056/nejm199310143291604

evidence_span

{"source_cache": "artifacts/coumarin-research/21462332.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "51d6682c94db1c278e08b499a03d6580c7a23d466c8faf9de1bcc30baaa36526", "start_char": 0, "end_char": 1240, "text_sha256": "51d6682c94db1c278e08b499a03d6580c7a23d466c8faf9de1bcc30baaa36526"}

experimental_model

Four-way crossover food-matrix bioavailability experiment

exposure

24 healthy volunteers; each formulation delivered 12 mg coumarin; urinary means n=23 over 8 hours

limitations

Urinary metabolite recovery is an absorption proxy, not absolute unchanged-coumarin bioavailability; single-dose study.

nutrient_topic

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

organism

Human

plain_language

This supplied the study comparison value.

primary_references

[coumarin-p21462332] Relative bioavailability of coumarin from cinnamon and cinnamon-containing foods compared to isolated coumarin: a four-way crossover study in human volunteers. (2011). https://pubmed.ncbi.nlm.nih.gov/21462332/ DOI: 10.1002/mnfr.201000394

tissue_or_cell_type

Urine and plasma

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 670–681

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Four-way crossover food-matrix bioavailability experiment · source_derived_draft · unverified_draft

### coumarin-capsule-recovery Isolated coumarin capsules produced 62.8% mean urinary 7-hydroxycoumarin recovery over eight hours. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This supplied the study comparison value. organism: Human tissue_or_cell_type: Urine and plasma experimental_model: Four-way crossover food-matrix bioavailability experiment limitations: Urinary metabolite recovery is an absorption proxy, not absolute unchanged-coumarin bioavailability; single-dose study. exposure: 24 healthy volunteers; each formulation delivered 12 mg coumarin; urinary means n=23 over 8 hours evidence_span: {"source_cache": "artifacts/coumarin-research/21462332.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "51d6682c94db1c278e08b499a03d6580c7a23d466c8faf9de1bcc30baaa36526", "start_char": 0, "end_char": 1240, "text_sha256": "51d6682c94db1c278e08b499a03d6580c7a23d466c8faf9de1bcc30baaa36526"} [coumarin-p21462332] Relative bioavailability of coumarin from cinnamon and cinnamon-containing foods compared to isolated coumarin: a four-way crossover study in human volunteers. (2011). https://pubmed.ncbi.nlm.nih.gov/21462332/ DOI: 10.1002/mnfr.201000394

evidence_span

{"source_cache": "artifacts/coumarin-research/3715206.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4433719cc63af1e4629ca9f419502d95915cd5e7455ea2343122af58ba4ef184", "start_char": 0, "end_char": 936, "text_sha256": "4433719cc63af1e4629ca9f419502d95915cd5e7455ea2343122af58ba4ef184"}

experimental_model

Morphology of cells attaching to implanted subcutaneous coverslips

exposure

Coumarin intervention; dose not stated in indexed abstract

limitations

Morphological recruitment/activation indices are not direct proof of a specific protease pathway or human benefit.

nutrient_topic

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

organism

Dog

plain_language

Immune-cell appearance changed in the animal tissue experiment.

primary_references

[coumarin-p3715206] The effect of coumarin (5,6 benzo-alpha-pyrone) on elicited members of the mononuclear system in dogs with chronic secondary lymphedema. (1986). https://pubmed.ncbi.nlm.nih.gov/3715206/ DOI: 10.1007/bf01851991

tissue_or_cell_type

Chronically lymphedematous tissues

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 306–317

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Morphology of cells attaching to implanted subcutaneous coverslips · source_derived_draft · unverified_draft

### coumarin-dog-macrophage-response Coumarin increased macrophage morphologies interpreted as recruitment and elicited activity in canine lymphedema. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Immune-cell appearance changed in the animal tissue experiment. organism: Dog tissue_or_cell_type: Chronically lymphedematous tissues experimental_model: Morphology of cells attaching to implanted subcutaneous coverslips limitations: Morphological recruitment/activation indices are not direct proof of a specific protease pathway or human benefit. exposure: Coumarin intervention; dose not stated in indexed abstract evidence_span: {"source_cache": "artifacts/coumarin-research/3715206.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4433719cc63af1e4629ca9f419502d95915cd5e7455ea2343122af58ba4ef184", "start_char": 0, "end_char": 936, "text_sha256": "4433719cc63af1e4629ca9f419502d95915cd5e7455ea2343122af58ba4ef184"} [coumarin-p3715206] The effect of coumarin (5,6 benzo-alpha-pyrone) on elicited members of the mononuclear system in dogs with chronic secondary lymphedema. (1986). https://pubmed.ncbi.nlm.nih.gov/3715206/ DOI: 10.1007/bf01851991

evidence_span

{"source_cache": "artifacts/coumarin-research/7263928.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a0e89cd9655c11d4758646e8e40305b497ba72eef60100f660deaa87390cd385", "start_char": 0, "end_char": 1084, "text_sha256": "a0e89cd9655c11d4758646e8e40305b497ba72eef60100f660deaa87390cd385"}

experimental_model

Pilot oral, sustained-release and intravenous pharmacokinetic comparison

exposure

Coumarin formulations; full dosing not specified in abstract

limitations

Pilot formulation comparison; low parent exposure does not imply poor intestinal absorption.

nutrient_topic

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

organism

Human

plain_language

Absorbed coumarin was largely transformed before circulating unchanged.

primary_references

[coumarin-p7263928] Pilot study on bioavailability of coumarin and 7-hydroxycoumarin upon peroral administration of coumarin in a sustained-release dosage form. (1981). https://pubmed.ncbi.nlm.nih.gov/7263928/ DOI: 10.1002/j.1552-4604.1981.tb01770.x

tissue_or_cell_type

Whole blood

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 644–655

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pilot oral, sustained-release and intravenous pharmacokinetic comparison · source_derived_draft · unverified_draft

### coumarin-first-pass Approximately 1% of orally administered coumarin reached systemic circulation unchanged in this pilot study. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Absorbed coumarin was largely transformed before circulating unchanged. organism: Human tissue_or_cell_type: Whole blood experimental_model: Pilot oral, sustained-release and intravenous pharmacokinetic comparison limitations: Pilot formulation comparison; low parent exposure does not imply poor intestinal absorption. exposure: Coumarin formulations; full dosing not specified in abstract evidence_span: {"source_cache": "artifacts/coumarin-research/7263928.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a0e89cd9655c11d4758646e8e40305b497ba72eef60100f660deaa87390cd385", "start_char": 0, "end_char": 1084, "text_sha256": "a0e89cd9655c11d4758646e8e40305b497ba72eef60100f660deaa87390cd385"} [coumarin-p7263928] Pilot study on bioavailability of coumarin and 7-hydroxycoumarin upon peroral administration of coumarin in a sustained-release dosage form. (1981). https://pubmed.ncbi.nlm.nih.gov/7263928/ DOI: 10.1002/j.1552-4604.1981.tb01770.x

evidence_span

{"source_cache": "artifacts/coumarin-research/18210747.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e78df713d6bc2e34f13e80a0ef04c217a176b5d6082cbb28fa5a62464fcce842", "start_char": 0, "end_char": 1237, "text_sha256": "e78df713d6bc2e34f13e80a0ef04c217a176b5d6082cbb28fa5a62464fcce842"}

experimental_model

Cell viability, cell cycle, protein and mitochondrial assays

exposure

Coumarin; reported viability IC50 54.2 micromolar

limitations

Cultured cancer-cell response does not establish treatment efficacy; indexed abstract does not specify all exposure durations.

nutrient_topic

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

organism

Human cell line

plain_language

Exposed cells stopped progressing through part of their division cycle.

primary_references

[coumarin-p18210747] Coumarin induces cell cycle arrest and apoptosis in human cervical cancer HeLa cells through a mitochondria- and caspase-3 dependent mechanism and NF-kappaB down-regulation. (2007). https://pubmed.ncbi.nlm.nih.gov/18210747/

tissue_or_cell_type

HeLa cervical cancer cells

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 319–330

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell viability, cell cycle, protein and mitochondrial assays · source_derived_draft · unverified_draft

### coumarin-hela-arrest Coumarin induced G0/G1 arrest in HeLa cells. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Exposed cells stopped progressing through part of their division cycle. organism: Human cell line tissue_or_cell_type: HeLa cervical cancer cells experimental_model: Cell viability, cell cycle, protein and mitochondrial assays limitations: Cultured cancer-cell response does not establish treatment efficacy; indexed abstract does not specify all exposure durations. exposure: Coumarin; reported viability IC50 54.2 micromolar evidence_span: {"source_cache": "artifacts/coumarin-research/18210747.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e78df713d6bc2e34f13e80a0ef04c217a176b5d6082cbb28fa5a62464fcce842", "start_char": 0, "end_char": 1237, "text_sha256": "e78df713d6bc2e34f13e80a0ef04c217a176b5d6082cbb28fa5a62464fcce842"} [coumarin-p18210747] Coumarin induces cell cycle arrest and apoptosis in human cervical cancer HeLa cells through a mitochondria- and caspase-3 dependent mechanism and NF-kappaB down-regulation. (2007). https://pubmed.ncbi.nlm.nih.gov/18210747/

evidence_span

{"source_cache": "artifacts/coumarin-research/18210747.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e78df713d6bc2e34f13e80a0ef04c217a176b5d6082cbb28fa5a62464fcce842", "start_char": 0, "end_char": 1237, "text_sha256": "e78df713d6bc2e34f13e80a0ef04c217a176b5d6082cbb28fa5a62464fcce842"}

experimental_model

Cell viability, cell cycle, protein and mitochondrial assays

exposure

Coumarin; reported viability IC50 54.2 micromolar

limitations

Cultured cancer-cell response does not establish treatment efficacy; indexed abstract does not specify all exposure durations.

nutrient_topic

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

organism

Human cell line

plain_language

A protein associated with mitochondrial apoptosis increased.

primary_references

[coumarin-p18210747] Coumarin induces cell cycle arrest and apoptosis in human cervical cancer HeLa cells through a mitochondria- and caspase-3 dependent mechanism and NF-kappaB down-regulation. (2007). https://pubmed.ncbi.nlm.nih.gov/18210747/

tissue_or_cell_type

HeLa cervical cancer cells

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 371–382

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell viability, cell cycle, protein and mitochondrial assays · source_derived_draft · unverified_draft

### coumarin-hela-bax Coumarin increased BAX expression in HeLa cells. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A protein associated with mitochondrial apoptosis increased. organism: Human cell line tissue_or_cell_type: HeLa cervical cancer cells experimental_model: Cell viability, cell cycle, protein and mitochondrial assays limitations: Cultured cancer-cell response does not establish treatment efficacy; indexed abstract does not specify all exposure durations. exposure: Coumarin; reported viability IC50 54.2 micromolar evidence_span: {"source_cache": "artifacts/coumarin-research/18210747.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e78df713d6bc2e34f13e80a0ef04c217a176b5d6082cbb28fa5a62464fcce842", "start_char": 0, "end_char": 1237, "text_sha256": "e78df713d6bc2e34f13e80a0ef04c217a176b5d6082cbb28fa5a62464fcce842"} [coumarin-p18210747] Coumarin induces cell cycle arrest and apoptosis in human cervical cancer HeLa cells through a mitochondria- and caspase-3 dependent mechanism and NF-kappaB down-regulation. (2007). https://pubmed.ncbi.nlm.nih.gov/18210747/

evidence_span

{"source_cache": "artifacts/coumarin-research/18210747.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e78df713d6bc2e34f13e80a0ef04c217a176b5d6082cbb28fa5a62464fcce842", "start_char": 0, "end_char": 1237, "text_sha256": "e78df713d6bc2e34f13e80a0ef04c217a176b5d6082cbb28fa5a62464fcce842"}

experimental_model

Cell viability, cell cycle, protein and mitochondrial assays

exposure

Coumarin; reported viability IC50 54.2 micromolar

limitations

Cultured cancer-cell response does not establish treatment efficacy; indexed abstract does not specify all exposure durations.

nutrient_topic

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

organism

Human cell line

plain_language

One cell-survival protein decreased.

primary_references

[coumarin-p18210747] Coumarin induces cell cycle arrest and apoptosis in human cervical cancer HeLa cells through a mitochondria- and caspase-3 dependent mechanism and NF-kappaB down-regulation. (2007). https://pubmed.ncbi.nlm.nih.gov/18210747/

tissue_or_cell_type

HeLa cervical cancer cells

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 345–356

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell viability, cell cycle, protein and mitochondrial assays · source_derived_draft · unverified_draft

### coumarin-hela-bcl2 Coumarin reduced BCL2 expression in HeLa cells. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: One cell-survival protein decreased. organism: Human cell line tissue_or_cell_type: HeLa cervical cancer cells experimental_model: Cell viability, cell cycle, protein and mitochondrial assays limitations: Cultured cancer-cell response does not establish treatment efficacy; indexed abstract does not specify all exposure durations. exposure: Coumarin; reported viability IC50 54.2 micromolar evidence_span: {"source_cache": "artifacts/coumarin-research/18210747.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e78df713d6bc2e34f13e80a0ef04c217a176b5d6082cbb28fa5a62464fcce842", "start_char": 0, "end_char": 1237, "text_sha256": "e78df713d6bc2e34f13e80a0ef04c217a176b5d6082cbb28fa5a62464fcce842"} [coumarin-p18210747] Coumarin induces cell cycle arrest and apoptosis in human cervical cancer HeLa cells through a mitochondria- and caspase-3 dependent mechanism and NF-kappaB down-regulation. (2007). https://pubmed.ncbi.nlm.nih.gov/18210747/

evidence_span

{"source_cache": "artifacts/coumarin-research/18210747.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e78df713d6bc2e34f13e80a0ef04c217a176b5d6082cbb28fa5a62464fcce842", "start_char": 0, "end_char": 1237, "text_sha256": "e78df713d6bc2e34f13e80a0ef04c217a176b5d6082cbb28fa5a62464fcce842"}

experimental_model

Cell viability, cell cycle, protein and mitochondrial assays

exposure

Coumarin; reported viability IC50 54.2 micromolar

limitations

Cultured cancer-cell response does not establish treatment efficacy; indexed abstract does not specify all exposure durations.

nutrient_topic

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

organism

Human cell line

plain_language

Another cell-survival protein decreased.

primary_references

[coumarin-p18210747] Coumarin induces cell cycle arrest and apoptosis in human cervical cancer HeLa cells through a mitochondria- and caspase-3 dependent mechanism and NF-kappaB down-regulation. (2007). https://pubmed.ncbi.nlm.nih.gov/18210747/

tissue_or_cell_type

HeLa cervical cancer cells

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 358–369

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell viability, cell cycle, protein and mitochondrial assays · source_derived_draft · unverified_draft

### coumarin-hela-bclxl Coumarin reduced Bcl-xL expression in HeLa cells. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Another cell-survival protein decreased. organism: Human cell line tissue_or_cell_type: HeLa cervical cancer cells experimental_model: Cell viability, cell cycle, protein and mitochondrial assays limitations: Cultured cancer-cell response does not establish treatment efficacy; indexed abstract does not specify all exposure durations. exposure: Coumarin; reported viability IC50 54.2 micromolar evidence_span: {"source_cache": "artifacts/coumarin-research/18210747.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e78df713d6bc2e34f13e80a0ef04c217a176b5d6082cbb28fa5a62464fcce842", "start_char": 0, "end_char": 1237, "text_sha256": "e78df713d6bc2e34f13e80a0ef04c217a176b5d6082cbb28fa5a62464fcce842"} [coumarin-p18210747] Coumarin induces cell cycle arrest and apoptosis in human cervical cancer HeLa cells through a mitochondria- and caspase-3 dependent mechanism and NF-kappaB down-regulation. (2007). https://pubmed.ncbi.nlm.nih.gov/18210747/

evidence_span

{"source_cache": "artifacts/coumarin-research/18210747.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e78df713d6bc2e34f13e80a0ef04c217a176b5d6082cbb28fa5a62464fcce842", "start_char": 0, "end_char": 1237, "text_sha256": "e78df713d6bc2e34f13e80a0ef04c217a176b5d6082cbb28fa5a62464fcce842"}

experimental_model

Cell viability, cell cycle, protein and mitochondrial assays

exposure

Coumarin; reported viability IC50 54.2 micromolar

limitations

Cultured cancer-cell response does not establish treatment efficacy; indexed abstract does not specify all exposure durations.

nutrient_topic

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

organism

Human cell line

plain_language

A cell-death execution enzyme became active.

primary_references

[coumarin-p18210747] Coumarin induces cell cycle arrest and apoptosis in human cervical cancer HeLa cells through a mitochondria- and caspase-3 dependent mechanism and NF-kappaB down-regulation. (2007). https://pubmed.ncbi.nlm.nih.gov/18210747/

tissue_or_cell_type

HeLa cervical cancer cells

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 397–408

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell viability, cell cycle, protein and mitochondrial assays · source_derived_draft · unverified_draft

### coumarin-hela-casp3 Coumarin activated caspase-3 in HeLa cells before apoptosis. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A cell-death execution enzyme became active. organism: Human cell line tissue_or_cell_type: HeLa cervical cancer cells experimental_model: Cell viability, cell cycle, protein and mitochondrial assays limitations: Cultured cancer-cell response does not establish treatment efficacy; indexed abstract does not specify all exposure durations. exposure: Coumarin; reported viability IC50 54.2 micromolar evidence_span: {"source_cache": "artifacts/coumarin-research/18210747.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e78df713d6bc2e34f13e80a0ef04c217a176b5d6082cbb28fa5a62464fcce842", "start_char": 0, "end_char": 1237, "text_sha256": "e78df713d6bc2e34f13e80a0ef04c217a176b5d6082cbb28fa5a62464fcce842"} [coumarin-p18210747] Coumarin induces cell cycle arrest and apoptosis in human cervical cancer HeLa cells through a mitochondria- and caspase-3 dependent mechanism and NF-kappaB down-regulation. (2007). https://pubmed.ncbi.nlm.nih.gov/18210747/

evidence_span

{"source_cache": "artifacts/coumarin-research/18210747.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e78df713d6bc2e34f13e80a0ef04c217a176b5d6082cbb28fa5a62464fcce842", "start_char": 0, "end_char": 1237, "text_sha256": "e78df713d6bc2e34f13e80a0ef04c217a176b5d6082cbb28fa5a62464fcce842"}

experimental_model

Cell viability, cell cycle, protein and mitochondrial assays

exposure

Coumarin; reported viability IC50 54.2 micromolar

limitations

Cultured cancer-cell response does not establish treatment efficacy; indexed abstract does not specify all exposure durations.

nutrient_topic

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

organism

Human cell line

plain_language

A mitochondrial signal entered the cell-death pathway.

primary_references

[coumarin-p18210747] Coumarin induces cell cycle arrest and apoptosis in human cervical cancer HeLa cells through a mitochondria- and caspase-3 dependent mechanism and NF-kappaB down-regulation. (2007). https://pubmed.ncbi.nlm.nih.gov/18210747/

tissue_or_cell_type

HeLa cervical cancer cells

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 384–395

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell viability, cell cycle, protein and mitochondrial assays · source_derived_draft · unverified_draft

### coumarin-hela-cytc Coumarin promoted cytochrome c release from HeLa mitochondria. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A mitochondrial signal entered the cell-death pathway. organism: Human cell line tissue_or_cell_type: HeLa cervical cancer cells experimental_model: Cell viability, cell cycle, protein and mitochondrial assays limitations: Cultured cancer-cell response does not establish treatment efficacy; indexed abstract does not specify all exposure durations. exposure: Coumarin; reported viability IC50 54.2 micromolar evidence_span: {"source_cache": "artifacts/coumarin-research/18210747.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e78df713d6bc2e34f13e80a0ef04c217a176b5d6082cbb28fa5a62464fcce842", "start_char": 0, "end_char": 1237, "text_sha256": "e78df713d6bc2e34f13e80a0ef04c217a176b5d6082cbb28fa5a62464fcce842"} [coumarin-p18210747] Coumarin induces cell cycle arrest and apoptosis in human cervical cancer HeLa cells through a mitochondria- and caspase-3 dependent mechanism and NF-kappaB down-regulation. (2007). https://pubmed.ncbi.nlm.nih.gov/18210747/

evidence_span

{"source_cache": "artifacts/coumarin-research/18210747.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e78df713d6bc2e34f13e80a0ef04c217a176b5d6082cbb28fa5a62464fcce842", "start_char": 0, "end_char": 1237, "text_sha256": "e78df713d6bc2e34f13e80a0ef04c217a176b5d6082cbb28fa5a62464fcce842"}

experimental_model

Cell viability, cell cycle, protein and mitochondrial assays

exposure

Coumarin; reported viability IC50 54.2 micromolar

limitations

Cultured cancer-cell response does not establish treatment efficacy; indexed abstract does not specify all exposure durations.

nutrient_topic

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

organism

Human cell line

plain_language

The mitochondrial electrical gradient weakened.

primary_references

[coumarin-p18210747] Coumarin induces cell cycle arrest and apoptosis in human cervical cancer HeLa cells through a mitochondria- and caspase-3 dependent mechanism and NF-kappaB down-regulation. (2007). https://pubmed.ncbi.nlm.nih.gov/18210747/

tissue_or_cell_type

HeLa cervical cancer cells

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 332–343

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell viability, cell cycle, protein and mitochondrial assays · source_derived_draft · unverified_draft

### coumarin-hela-depolarization Coumarin dose-dependently reduced HeLa mitochondrial membrane potential. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The mitochondrial electrical gradient weakened. organism: Human cell line tissue_or_cell_type: HeLa cervical cancer cells experimental_model: Cell viability, cell cycle, protein and mitochondrial assays limitations: Cultured cancer-cell response does not establish treatment efficacy; indexed abstract does not specify all exposure durations. exposure: Coumarin; reported viability IC50 54.2 micromolar evidence_span: {"source_cache": "artifacts/coumarin-research/18210747.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e78df713d6bc2e34f13e80a0ef04c217a176b5d6082cbb28fa5a62464fcce842", "start_char": 0, "end_char": 1237, "text_sha256": "e78df713d6bc2e34f13e80a0ef04c217a176b5d6082cbb28fa5a62464fcce842"} [coumarin-p18210747] Coumarin induces cell cycle arrest and apoptosis in human cervical cancer HeLa cells through a mitochondria- and caspase-3 dependent mechanism and NF-kappaB down-regulation. (2007). https://pubmed.ncbi.nlm.nih.gov/18210747/

evidence_span

{"source_cache": "artifacts/coumarin-research/7510710.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "723ca14ffacb7f7130fb0ae13e07174266395023f131be84d7b6a308c38dd21b", "start_char": 0, "end_char": 1368, "text_sha256": "723ca14ffacb7f7130fb0ae13e07174266395023f131be84d7b6a308c38dd21b"}

experimental_model

Dose/time exposure and washout in malignant cell lines

exposure

Coumarin and 7-hydroxycoumarin in cell culture

limitations

Cell-type-specific responses; no clinical anticancer efficacy inferred; concentrations not specified in indexed abstract.

nutrient_topic

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

organism

Human cell lines

plain_language

The cell-death result depended on the cell line.

primary_references

[coumarin-p7510710] Growth-inhibitory effects of coumarin (1,2-benzopyrone) and 7-hydroxycoumarin on human malignant cell lines in vitro. (1994). https://pubmed.ncbi.nlm.nih.gov/7510710/ DOI: 10.1007/bf01377114

tissue_or_cell_type

Study panel including HL-60, A549, LNCaP and other tumor lines

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 436–447

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dose/time exposure and washout in malignant cell lines · source_derived_draft · unverified_draft

### coumarin-hl60-parent-apoptosis Coumarin stimulated apoptosis in HL-60, but not the other cell lines tested in this study. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cell-death result depended on the cell line. organism: Human cell lines tissue_or_cell_type: Study panel including HL-60, A549, LNCaP and other tumor lines experimental_model: Dose/time exposure and washout in malignant cell lines limitations: Cell-type-specific responses; no clinical anticancer efficacy inferred; concentrations not specified in indexed abstract. exposure: Coumarin and 7-hydroxycoumarin in cell culture evidence_span: {"source_cache": "artifacts/coumarin-research/7510710.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "723ca14ffacb7f7130fb0ae13e07174266395023f131be84d7b6a308c38dd21b", "start_char": 0, "end_char": 1368, "text_sha256": "723ca14ffacb7f7130fb0ae13e07174266395023f131be84d7b6a308c38dd21b"} [coumarin-p7510710] Growth-inhibitory effects of coumarin (1,2-benzopyrone) and 7-hydroxycoumarin on human malignant cell lines in vitro. (1994). https://pubmed.ncbi.nlm.nih.gov/7510710/ DOI: 10.1007/bf01377114

evidence_span

{"source_cache": "artifacts/coumarin-research/7263928.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a0e89cd9655c11d4758646e8e40305b497ba72eef60100f660deaa87390cd385", "start_char": 0, "end_char": 1084, "text_sha256": "a0e89cd9655c11d4758646e8e40305b497ba72eef60100f660deaa87390cd385"}

experimental_model

Pilot oral, sustained-release and intravenous pharmacokinetic comparison

exposure

Coumarin formulations; full dosing not specified in abstract

limitations

Pilot formulation comparison; low parent exposure does not imply poor intestinal absorption.

nutrient_topic

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

organism

Human

plain_language

The conjugated metabolite records processing of the swallowed compound.

primary_references

[coumarin-p7263928] Pilot study on bioavailability of coumarin and 7-hydroxycoumarin upon peroral administration of coumarin in a sustained-release dosage form. (1981). https://pubmed.ncbi.nlm.nih.gov/7263928/ DOI: 10.1002/j.1552-4604.1981.tb01770.x

tissue_or_cell_type

Whole blood

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 657–668

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pilot oral, sustained-release and intravenous pharmacokinetic comparison · source_derived_draft · unverified_draft

### coumarin-human-glucuronide 7-Hydroxycoumarin glucuronide was measured after oral coumarin, supporting extensive absorption and first-pass metabolism. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The conjugated metabolite records processing of the swallowed compound. organism: Human tissue_or_cell_type: Whole blood experimental_model: Pilot oral, sustained-release and intravenous pharmacokinetic comparison limitations: Pilot formulation comparison; low parent exposure does not imply poor intestinal absorption. exposure: Coumarin formulations; full dosing not specified in abstract evidence_span: {"source_cache": "artifacts/coumarin-research/7263928.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a0e89cd9655c11d4758646e8e40305b497ba72eef60100f660deaa87390cd385", "start_char": 0, "end_char": 1084, "text_sha256": "a0e89cd9655c11d4758646e8e40305b497ba72eef60100f660deaa87390cd385"} [coumarin-p7263928] Pilot study on bioavailability of coumarin and 7-hydroxycoumarin upon peroral administration of coumarin in a sustained-release dosage form. (1981). https://pubmed.ncbi.nlm.nih.gov/7263928/ DOI: 10.1002/j.1552-4604.1981.tb01770.x

evidence_span

{"source_cache": "artifacts/coumarin-research/8377779.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d4b9a301f1334d388b1469a12453ee1af75bcb87f52277dbfac03bcdb045c9ad", "start_char": 0, "end_char": 1907, "text_sha256": "d4b9a301f1334d388b1469a12453ee1af75bcb87f52277dbfac03bcdb045c9ad"}

experimental_model

Randomized double-blind placebo-controlled crossover trial

exposure

Coumarin 400 mg/day and placebo, six months each

limitations

Small older mixed-population trial; positive arm finding was not reproduced in the larger subsequent study.

nutrient_topic

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

organism

Human

plain_language

The same trial reported less leg swelling.

primary_references

[coumarin-p8377779] Treatment of lymphedema of the arms and legs with 5,6-benzo-[alpha]-pyrone. (1993). https://pubmed.ncbi.nlm.nih.gov/8377779/ DOI: 10.1056/nejm199310143291604

tissue_or_cell_type

31 postmastectomy arm and 21 other-cause leg lymphedema patients

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 748–759

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind placebo-controlled crossover trial · source_derived_draft · unverified_draft

### coumarin-leg-positive Leg edema declined from 25% to 17% above normal in the 1993 trial (P<0.001). Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same trial reported less leg swelling. organism: Human tissue_or_cell_type: 31 postmastectomy arm and 21 other-cause leg lymphedema patients experimental_model: Randomized double-blind placebo-controlled crossover trial limitations: Small older mixed-population trial; positive arm finding was not reproduced in the larger subsequent study. exposure: Coumarin 400 mg/day and placebo, six months each evidence_span: {"source_cache": "artifacts/coumarin-research/8377779.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d4b9a301f1334d388b1469a12453ee1af75bcb87f52277dbfac03bcdb045c9ad", "start_char": 0, "end_char": 1907, "text_sha256": "d4b9a301f1334d388b1469a12453ee1af75bcb87f52277dbfac03bcdb045c9ad"} [coumarin-p8377779] Treatment of lymphedema of the arms and legs with 5,6-benzo-[alpha]-pyrone. (1993). https://pubmed.ncbi.nlm.nih.gov/8377779/ DOI: 10.1056/nejm199310143291604

evidence_span

{"source_cache": "artifacts/coumarin-research/9929524.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6d6d4760bdd321dda87f82927c5dfcc7120ed963c101d799473ed53ff4c7764b", "start_char": 0, "end_char": 1579, "text_sha256": "6d6d4760bdd321dda87f82927c5dfcc7120ed963c101d799473ed53ff4c7764b"}

experimental_model

Randomized placebo-controlled crossover replication trial

exposure

Coumarin 200 mg twice daily versus placebo, six months each

limitations

Specific disease population and pharmacological exposure; liver-test incidence cannot be extrapolated to food doses.

nutrient_topic

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

organism

Human

plain_language

Liver injury signals appeared at this treatment exposure.

primary_references

[coumarin-p9929524] Lack of effect of coumarin in women with lymphedema after treatment for breast cancer. (1999). https://pubmed.ncbi.nlm.nih.gov/9929524/ DOI: 10.1056/nejm199902043400503

tissue_or_cell_type

140 women with chronic arm lymphedema after breast cancer treatment

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 787–798

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized placebo-controlled crossover replication trial · source_derived_draft · unverified_draft

### coumarin-liver-toxicity Serologic liver toxicity occurred in 6% of women during the coumarin trial. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Liver injury signals appeared at this treatment exposure. organism: Human tissue_or_cell_type: 140 women with chronic arm lymphedema after breast cancer treatment experimental_model: Randomized placebo-controlled crossover replication trial limitations: Specific disease population and pharmacological exposure; liver-test incidence cannot be extrapolated to food doses. exposure: Coumarin 200 mg twice daily versus placebo, six months each evidence_span: {"source_cache": "artifacts/coumarin-research/9929524.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6d6d4760bdd321dda87f82927c5dfcc7120ed963c101d799473ed53ff4c7764b", "start_char": 0, "end_char": 1579, "text_sha256": "6d6d4760bdd321dda87f82927c5dfcc7120ed963c101d799473ed53ff4c7764b"} [coumarin-p9929524] Lack of effect of coumarin in women with lymphedema after treatment for breast cancer. (1999). https://pubmed.ncbi.nlm.nih.gov/9929524/ DOI: 10.1056/nejm199902043400503

evidence_span

{"source_cache": "artifacts/coumarin-research/7839702.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ca24fcb6d3561aa6605b2a53ff463aa6e2ca085d785d1f77615498580d84e909", "start_char": 0, "end_char": 1457, "text_sha256": "ca24fcb6d3561aa6605b2a53ff463aa6e2ca085d785d1f77615498580d84e909"}

experimental_model

Radiolabeled substrate metabolism in 12 human liver microsomal samples

exposure

50 micromolar [3-14C]coumarin

limitations

Donor-panel correlations do not assign enzyme causality; older grouping of 3-hydroxylation products is not adopted as an epoxide mechanism.

nutrient_topic

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

organism

Human

plain_language

A small measured fraction became attached to proteins.

primary_references

[coumarin-p7839702] Metabolism of [3-14C] coumarin by human liver microsomes. (1994). https://pubmed.ncbi.nlm.nih.gov/7839702/ DOI: 10.3109/00498259409043279

tissue_or_cell_type

Liver microsomes

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 202–213

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Radiolabeled substrate metabolism in 12 human liver microsomal samples · source_derived_draft · unverified_draft

### coumarin-microsomal-binding Coumarin-derived material bound covalently to human microsomal proteins, averaging 4.8 pmol/min/mg. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A small measured fraction became attached to proteins. organism: Human tissue_or_cell_type: Liver microsomes experimental_model: Radiolabeled substrate metabolism in 12 human liver microsomal samples limitations: Donor-panel correlations do not assign enzyme causality; older grouping of 3-hydroxylation products is not adopted as an epoxide mechanism. exposure: 50 micromolar [3-14C]coumarin evidence_span: {"source_cache": "artifacts/coumarin-research/7839702.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ca24fcb6d3561aa6605b2a53ff463aa6e2ca085d785d1f77615498580d84e909", "start_char": 0, "end_char": 1457, "text_sha256": "ca24fcb6d3561aa6605b2a53ff463aa6e2ca085d785d1f77615498580d84e909"} [coumarin-p7839702] Metabolism of [3-14C] coumarin by human liver microsomes. (1994). https://pubmed.ncbi.nlm.nih.gov/7839702/ DOI: 10.3109/00498259409043279

evidence_span

{"source_cache": "artifacts/coumarin-research/7839702.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ca24fcb6d3561aa6605b2a53ff463aa6e2ca085d785d1f77615498580d84e909", "start_char": 0, "end_char": 1457, "text_sha256": "ca24fcb6d3561aa6605b2a53ff463aa6e2ca085d785d1f77615498580d84e909"}

experimental_model

Radiolabeled substrate metabolism in 12 human liver microsomal samples

exposure

50 micromolar [3-14C]coumarin

limitations

Donor-panel correlations do not assign enzyme causality; older grouping of 3-hydroxylation products is not adopted as an epoxide mechanism.

nutrient_topic

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

organism

Human

plain_language

Most measured polar product was 7-hydroxycoumarin in this experiment.

primary_references

[coumarin-p7839702] Metabolism of [3-14C] coumarin by human liver microsomes. (1994). https://pubmed.ncbi.nlm.nih.gov/7839702/ DOI: 10.3109/00498259409043279

tissue_or_cell_type

Liver microsomes

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 189–200

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Radiolabeled substrate metabolism in 12 human liver microsomal samples · source_derived_draft · unverified_draft

### coumarin-microsomal-main-product Mean 7-hydroxycoumarin formation was 1230 of 1420 pmol/min/mg total polar products in the 12-sample human microsomal panel. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Most measured polar product was 7-hydroxycoumarin in this experiment. organism: Human tissue_or_cell_type: Liver microsomes experimental_model: Radiolabeled substrate metabolism in 12 human liver microsomal samples limitations: Donor-panel correlations do not assign enzyme causality; older grouping of 3-hydroxylation products is not adopted as an epoxide mechanism. exposure: 50 micromolar [3-14C]coumarin evidence_span: {"source_cache": "artifacts/coumarin-research/7839702.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ca24fcb6d3561aa6605b2a53ff463aa6e2ca085d785d1f77615498580d84e909", "start_char": 0, "end_char": 1457, "text_sha256": "ca24fcb6d3561aa6605b2a53ff463aa6e2ca085d785d1f77615498580d84e909"} [coumarin-p7839702] Metabolism of [3-14C] coumarin by human liver microsomes. (1994). https://pubmed.ncbi.nlm.nih.gov/7839702/ DOI: 10.3109/00498259409043279

evidence_span

{"source_cache": "artifacts/coumarin-research/9583093.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dd691821bbdc859459d1373d8150a4579e13a0110f2d2bf1880cd895a99c5957", "start_char": 0, "end_char": 779, "text_sha256": "dd691821bbdc859459d1373d8150a4579e13a0110f2d2bf1880cd895a99c5957"}

experimental_model

Comparative proliferation assays of parent, hydroxylated and glucuronidated compound

exposure

Parent IC50 1.59–3.57 mM; 7-hydroxy metabolite IC50 0.68–2.69 mM

limitations

High in vitro concentrations; effects cannot be assumed at food exposure or across cell types.

nutrient_topic

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

organism

Human cell lines

plain_language

This experiment required millimolar parent concentrations.

primary_references

[coumarin-p9583093] Antitumor-activities of coumarin, 7-hydroxy-coumarin and its glucuronide in several human tumor cell lines. (1998). https://pubmed.ncbi.nlm.nih.gov/9583093/

tissue_or_cell_type

Gastric carcinoma, Caco-2, HepG2 and CCRF-CEM cells

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 449–460

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Comparative proliferation assays of parent, hydroxylated and glucuronidated compound · source_derived_draft · unverified_draft

### coumarin-millimolar-parent Coumarin inhibited proliferation with IC50 values of 1.59–3.57 mM across this four-cell-line panel. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This experiment required millimolar parent concentrations. organism: Human cell lines tissue_or_cell_type: Gastric carcinoma, Caco-2, HepG2 and CCRF-CEM cells experimental_model: Comparative proliferation assays of parent, hydroxylated and glucuronidated compound limitations: High in vitro concentrations; effects cannot be assumed at food exposure or across cell types. exposure: Parent IC50 1.59–3.57 mM; 7-hydroxy metabolite IC50 0.68–2.69 mM evidence_span: {"source_cache": "artifacts/coumarin-research/9583093.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dd691821bbdc859459d1373d8150a4579e13a0110f2d2bf1880cd895a99c5957", "start_char": 0, "end_char": 779, "text_sha256": "dd691821bbdc859459d1373d8150a4579e13a0110f2d2bf1880cd895a99c5957"} [coumarin-p9583093] Antitumor-activities of coumarin, 7-hydroxy-coumarin and its glucuronide in several human tumor cell lines. (1998). https://pubmed.ncbi.nlm.nih.gov/9583093/

evidence_span

{"source_cache": "artifacts/coumarin-research/7510710.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "723ca14ffacb7f7130fb0ae13e07174266395023f131be84d7b6a308c38dd21b", "start_char": 0, "end_char": 1368, "text_sha256": "723ca14ffacb7f7130fb0ae13e07174266395023f131be84d7b6a308c38dd21b"}

experimental_model

Dose/time exposure and washout in malignant cell lines

exposure

Coumarin and 7-hydroxycoumarin in cell culture

limitations

Cell-type-specific responses; no clinical anticancer efficacy inferred; concentrations not specified in indexed abstract.

nutrient_topic

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

organism

Human cell lines

plain_language

Growth slowing could reverse when exposure stopped.

primary_references

[coumarin-p7510710] Growth-inhibitory effects of coumarin (1,2-benzopyrone) and 7-hydroxycoumarin on human malignant cell lines in vitro. (1994). https://pubmed.ncbi.nlm.nih.gov/7510710/ DOI: 10.1007/bf01377114

tissue_or_cell_type

Study panel including HL-60, A549, LNCaP and other tumor lines

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 410–421

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dose/time exposure and washout in malignant cell lines · source_derived_draft · unverified_draft

### coumarin-parent-cytostasis Coumarin inhibited proliferation reversibly after drug removal in the tested malignant cell panel. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Growth slowing could reverse when exposure stopped. organism: Human cell lines tissue_or_cell_type: Study panel including HL-60, A549, LNCaP and other tumor lines experimental_model: Dose/time exposure and washout in malignant cell lines limitations: Cell-type-specific responses; no clinical anticancer efficacy inferred; concentrations not specified in indexed abstract. exposure: Coumarin and 7-hydroxycoumarin in cell culture evidence_span: {"source_cache": "artifacts/coumarin-research/7510710.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "723ca14ffacb7f7130fb0ae13e07174266395023f131be84d7b6a308c38dd21b", "start_char": 0, "end_char": 1368, "text_sha256": "723ca14ffacb7f7130fb0ae13e07174266395023f131be84d7b6a308c38dd21b"} [coumarin-p7510710] Growth-inhibitory effects of coumarin (1,2-benzopyrone) and 7-hydroxycoumarin on human malignant cell lines in vitro. (1994). https://pubmed.ncbi.nlm.nih.gov/7510710/ DOI: 10.1007/bf01377114

evidence_span

{"source_cache": "artifacts/coumarin-research/8377779.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d4b9a301f1334d388b1469a12453ee1af75bcb87f52277dbfac03bcdb045c9ad", "start_char": 0, "end_char": 1907, "text_sha256": "d4b9a301f1334d388b1469a12453ee1af75bcb87f52277dbfac03bcdb045c9ad"}

experimental_model

Randomized double-blind placebo-controlled crossover trial

exposure

Coumarin 400 mg/day and placebo, six months each

limitations

Small older mixed-population trial; positive arm finding was not reproduced in the larger subsequent study.

nutrient_topic

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

organism

Human

plain_language

Parent coumarin is not warfarin.

primary_references

[coumarin-p8377779] Treatment of lymphedema of the arms and legs with 5,6-benzo-[alpha]-pyrone. (1993). https://pubmed.ncbi.nlm.nih.gov/8377779/ DOI: 10.1056/nejm199310143291604

tissue_or_cell_type

31 postmastectomy arm and 21 other-cause leg lymphedema patients

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 722–733

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind placebo-controlled crossover trial · source_derived_draft · unverified_draft

### coumarin-parent-not-anticoagulant The study explicitly distinguished parent 1,2-benzopyrone from anticoagulant coumarin derivatives. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Parent coumarin is not warfarin. organism: Human tissue_or_cell_type: 31 postmastectomy arm and 21 other-cause leg lymphedema patients experimental_model: Randomized double-blind placebo-controlled crossover trial limitations: Small older mixed-population trial; positive arm finding was not reproduced in the larger subsequent study. exposure: Coumarin 400 mg/day and placebo, six months each evidence_span: {"source_cache": "artifacts/coumarin-research/8377779.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d4b9a301f1334d388b1469a12453ee1af75bcb87f52277dbfac03bcdb045c9ad", "start_char": 0, "end_char": 1907, "text_sha256": "d4b9a301f1334d388b1469a12453ee1af75bcb87f52277dbfac03bcdb045c9ad"} [coumarin-p8377779] Treatment of lymphedema of the arms and legs with 5,6-benzo-[alpha]-pyrone. (1993). https://pubmed.ncbi.nlm.nih.gov/8377779/ DOI: 10.1056/nejm199310143291604

evidence_span

{"source_cache": "artifacts/coumarin-research/1212425.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6bb270c1b4bf1aecb2d3340d80c5721afe0bdfab2db86ce53384dce46fa75db1", "start_char": 0, "end_char": 976, "text_sha256": "6bb270c1b4bf1aecb2d3340d80c5721afe0bdfab2db86ce53384dce46fa75db1"}

experimental_model

Protein clearance compared with nonmetabolizable PVP tracer

exposure

Experimental coumarin treatment; dose not stated in indexed abstract

limitations

Proteolysis is the authors proposed explanation; individual proteases were not identified in the abstract.

nutrient_topic

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

organism

Rat

plain_language

Breaking down trapped proteins was proposed to help fluid leave tissue.

primary_references

[coumarin-p1212425] The effect of coumarin on protein and PVP clearance from rat legs with various high protein oedemas. (1975). https://pubmed.ncbi.nlm.nih.gov/1212425/

tissue_or_cell_type

Normal, burned and lymph-edematous leg tissues

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 293–304

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Protein clearance compared with nonmetabolizable PVP tracer · source_derived_draft · unverified_draft

### coumarin-rat-protein-clearance Coumarin accelerated tissue protein removal relative to nonmetabolizable PVP in rat edema models; enhanced proteolysis was proposed. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Breaking down trapped proteins was proposed to help fluid leave tissue. organism: Rat tissue_or_cell_type: Normal, burned and lymph-edematous leg tissues experimental_model: Protein clearance compared with nonmetabolizable PVP tracer limitations: Proteolysis is the authors proposed explanation; individual proteases were not identified in the abstract. exposure: Experimental coumarin treatment; dose not stated in indexed abstract evidence_span: {"source_cache": "artifacts/coumarin-research/1212425.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6bb270c1b4bf1aecb2d3340d80c5721afe0bdfab2db86ce53384dce46fa75db1", "start_char": 0, "end_char": 976, "text_sha256": "6bb270c1b4bf1aecb2d3340d80c5721afe0bdfab2db86ce53384dce46fa75db1"} [coumarin-p1212425] The effect of coumarin on protein and PVP clearance from rat legs with various high protein oedemas. (1975). https://pubmed.ncbi.nlm.nih.gov/1212425/

evidence_span

{"source_cache": "artifacts/coumarin-research/9929524.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6d6d4760bdd321dda87f82927c5dfcc7120ed963c101d799473ed53ff4c7764b", "start_char": 0, "end_char": 1579, "text_sha256": "6d6d4760bdd321dda87f82927c5dfcc7120ed963c101d799473ed53ff4c7764b"}

experimental_model

Randomized placebo-controlled crossover replication trial

exposure

Coumarin 200 mg twice daily versus placebo, six months each

limitations

Specific disease population and pharmacological exposure; liver-test incidence cannot be extrapolated to food doses.

nutrient_topic

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

organism

Human

plain_language

Patient reports did not show a significant benefit.

primary_references

[coumarin-p9929524] Lack of effect of coumarin in women with lymphedema after treatment for breast cancer. (1999). https://pubmed.ncbi.nlm.nih.gov/9929524/ DOI: 10.1056/nejm199902043400503

tissue_or_cell_type

140 women with chronic arm lymphedema after breast cancer treatment

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 774–785

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized placebo-controlled crossover replication trial · source_derived_draft · unverified_draft

### coumarin-symptoms-null Moderate/large reported benefit occurred in 15% on coumarin versus 10% on placebo (P=0.19). Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Patient reports did not show a significant benefit. organism: Human tissue_or_cell_type: 140 women with chronic arm lymphedema after breast cancer treatment experimental_model: Randomized placebo-controlled crossover replication trial limitations: Specific disease population and pharmacological exposure; liver-test incidence cannot be extrapolated to food doses. exposure: Coumarin 200 mg twice daily versus placebo, six months each evidence_span: {"source_cache": "artifacts/coumarin-research/9929524.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6d6d4760bdd321dda87f82927c5dfcc7120ed963c101d799473ed53ff4c7764b", "start_char": 0, "end_char": 1579, "text_sha256": "6d6d4760bdd321dda87f82927c5dfcc7120ed963c101d799473ed53ff4c7764b"} [coumarin-p9929524] Lack of effect of coumarin in women with lymphedema after treatment for breast cancer. (1999). https://pubmed.ncbi.nlm.nih.gov/9929524/ DOI: 10.1056/nejm199902043400503

evidence_span

{"source_cache": "artifacts/ceylon-research/23627682.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7d3f2b3624550aeea2fde2ed51c9700a7e00e7dacf8e72fc242733dd0eb84161", "start_char": 0, "end_char": 1273, "text_sha256": "7d3f2b3624550aeea2fde2ed51c9700a7e00e7dacf8e72fc242733dd0eb84161"}

experimental_model

UPLC-UV/MS authenticated bark and retail-product analysis

exposure

Analytical sampling; no administered human dose

limitations

Botanical identity and product-specific composition matter; traces do not mean zero, and retail products need not be Ceylon.

nutrient_topic

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

organism

Cinnamomum verum, cassia, loureiroi and burmannii

plain_language

Ceylon generally had much less coumarin in these samples; the species and product still need checking.

primary_references

[ceylon-p23627682] Cassia cinnamon as a source of coumarin in cinnamon-flavored food and food supplements in the United States. (2013). https://pubmed.ncbi.nlm.nih.gov/23627682/ DOI: 10.1021/jf4005862

tissue_or_cell_type

Bark and commercial cinnamon foods/supplements

Ceylon cinnamon: metabolism, signaling and nutrient connections (2026-09-17) · lines 90–101

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · UPLC-UV/MS authenticated bark and retail-product analysis · source_derived_draft · unverified_draft

### ceylon-coumarin Authenticated C. verum bark contained only trace coumarin, whereas the tested cassia-type species contained substantial amounts. Condition category: normal nutrient_topic: Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect. plain_language: Ceylon generally had much less coumarin in these samples; the species and product still need checking. organism: Cinnamomum verum, cassia, loureiroi and burmannii tissue_or_cell_type: Bark and commercial cinnamon foods/supplements experimental_model: UPLC-UV/MS authenticated bark and retail-product analysis limitations: Botanical identity and product-specific composition matter; traces do not mean zero, and retail products need not be Ceylon. exposure: Analytical sampling; no administered human dose evidence_span: {"source_cache": "artifacts/ceylon-research/23627682.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7d3f2b3624550aeea2fde2ed51c9700a7e00e7dacf8e72fc242733dd0eb84161", "start_char": 0, "end_char": 1273, "text_sha256": "7d3f2b3624550aeea2fde2ed51c9700a7e00e7dacf8e72fc242733dd0eb84161"} [ceylon-p23627682] Cassia cinnamon as a source of coumarin in cinnamon-flavored food and food supplements in the United States. (2013). https://pubmed.ncbi.nlm.nih.gov/23627682/ DOI: 10.1021/jf4005862

evidence_span

{"source_cache": "artifacts/coumarin-research/16086027.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "df98434feed879e206e54c520d496e9711581107f6aec58bd9dcc1c74ed5d49d", "start_char": 0, "end_char": 532, "text_sha256": "df98434feed879e206e54c520d496e9711581107f6aec58bd9dcc1c74ed5d49d"}

experimental_model

X-ray structures of ligand-bound human CYP2A6

exposure

Coumarin and methoxsalen-bound structures

limitations

Structure demonstrates binding geometry, not clinical effects or dietary iron responsiveness.

nutrient_topic

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

organism

Human protein

plain_language

The enzyme holds coumarin in a specific orientation.

primary_references

[coumarin-p16086027] Structures of human microsomal cytochrome P450 2A6 complexed with coumarin and methoxsalen. (2005). https://pubmed.ncbi.nlm.nih.gov/16086027/ DOI: 10.1038/nsmb971

tissue_or_cell_type

CYP2A6 active site

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 163–174

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · X-ray structures of ligand-bound human CYP2A6 · source_derived_draft · unverified_draft

### coumarin-binding-orientation CYP2A6 Asn297 hydrogen bonding oriented coumarin within a compact hydrophobic active site for position-selective oxidation. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The enzyme holds coumarin in a specific orientation. organism: Human protein tissue_or_cell_type: CYP2A6 active site experimental_model: X-ray structures of ligand-bound human CYP2A6 limitations: Structure demonstrates binding geometry, not clinical effects or dietary iron responsiveness. exposure: Coumarin and methoxsalen-bound structures evidence_span: {"source_cache": "artifacts/coumarin-research/16086027.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "df98434feed879e206e54c520d496e9711581107f6aec58bd9dcc1c74ed5d49d", "start_char": 0, "end_char": 532, "text_sha256": "df98434feed879e206e54c520d496e9711581107f6aec58bd9dcc1c74ed5d49d"} [coumarin-p16086027] Structures of human microsomal cytochrome P450 2A6 complexed with coumarin and methoxsalen. (2005). https://pubmed.ncbi.nlm.nih.gov/16086027/ DOI: 10.1038/nsmb971

evidence_span

{"source_cache": "artifacts/coumarin-research/11950775.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "98a03fafa68ef4d55593a3b725af646175a11b42ce02b1dfe02be84ff49d4861", "start_char": 0, "end_char": 1158, "text_sha256": "98a03fafa68ef4d55593a3b725af646175a11b42ce02b1dfe02be84ff49d4861"}

experimental_model

Recombinant CYP enzymes, immunoinhibition and mouse lung inhibitor experiments

exposure

CYP1A/2E antibody inhibition and 5-phenyl-pentyne lung experiments

limitations

Relative contributions depend on species and tissue; this is not a clinical drug-interaction study.

nutrient_topic

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

organism

Human, rat and mouse; each claim specifies enzyme origin

plain_language

CYP1A1 can route coumarin toward a reactive intermediate.

primary_references

[coumarin-p11950775] Identification of the cytochromes P450 that catalyze coumarin 3,4-epoxidation and 3-hydroxylation. (2002). https://pubmed.ncbi.nlm.nih.gov/11950775/ DOI: 10.1124/dmd.30.5.483

tissue_or_cell_type

Liver and lung microsomes

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 215–226

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant CYP enzymes, immunoinhibition and mouse lung inhibitor experiments · source_derived_draft · unverified_draft

### coumarin-1a1-epoxide Recombinant human CYP1A enzymes catalyzed coumarin epoxidation; CYP1A1 was among the tested human forms. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: CYP1A1 can route coumarin toward a reactive intermediate. organism: Human, rat and mouse; each claim specifies enzyme origin tissue_or_cell_type: Liver and lung microsomes experimental_model: Recombinant CYP enzymes, immunoinhibition and mouse lung inhibitor experiments limitations: Relative contributions depend on species and tissue; this is not a clinical drug-interaction study. exposure: CYP1A/2E antibody inhibition and 5-phenyl-pentyne lung experiments evidence_span: {"source_cache": "artifacts/coumarin-research/11950775.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "98a03fafa68ef4d55593a3b725af646175a11b42ce02b1dfe02be84ff49d4861", "start_char": 0, "end_char": 1158, "text_sha256": "98a03fafa68ef4d55593a3b725af646175a11b42ce02b1dfe02be84ff49d4861"} [coumarin-p11950775] Identification of the cytochromes P450 that catalyze coumarin 3,4-epoxidation and 3-hydroxylation. (2002). https://pubmed.ncbi.nlm.nih.gov/11950775/ DOI: 10.1124/dmd.30.5.483

evidence_span

{"source_cache": "artifacts/coumarin-research/11950775.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "98a03fafa68ef4d55593a3b725af646175a11b42ce02b1dfe02be84ff49d4861", "start_char": 0, "end_char": 1158, "text_sha256": "98a03fafa68ef4d55593a3b725af646175a11b42ce02b1dfe02be84ff49d4861"}

experimental_model

Recombinant CYP enzymes, immunoinhibition and mouse lung inhibitor experiments

exposure

CYP1A/2E antibody inhibition and 5-phenyl-pentyne lung experiments

limitations

Relative contributions depend on species and tissue; this is not a clinical drug-interaction study.

nutrient_topic

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

organism

Human, rat and mouse; each claim specifies enzyme origin

plain_language

CYP1A2 provides another route to the reactive intermediate.

primary_references

[coumarin-p11950775] Identification of the cytochromes P450 that catalyze coumarin 3,4-epoxidation and 3-hydroxylation. (2002). https://pubmed.ncbi.nlm.nih.gov/11950775/ DOI: 10.1124/dmd.30.5.483

tissue_or_cell_type

Liver and lung microsomes

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 228–239

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant CYP enzymes, immunoinhibition and mouse lung inhibitor experiments · source_derived_draft · unverified_draft

### coumarin-1a2-epoxide Recombinant human CYP1A2 catalyzed coumarin 3,4-epoxide formation. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: CYP1A2 provides another route to the reactive intermediate. organism: Human, rat and mouse; each claim specifies enzyme origin tissue_or_cell_type: Liver and lung microsomes experimental_model: Recombinant CYP enzymes, immunoinhibition and mouse lung inhibitor experiments limitations: Relative contributions depend on species and tissue; this is not a clinical drug-interaction study. exposure: CYP1A/2E antibody inhibition and 5-phenyl-pentyne lung experiments evidence_span: {"source_cache": "artifacts/coumarin-research/11950775.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "98a03fafa68ef4d55593a3b725af646175a11b42ce02b1dfe02be84ff49d4861", "start_char": 0, "end_char": 1158, "text_sha256": "98a03fafa68ef4d55593a3b725af646175a11b42ce02b1dfe02be84ff49d4861"} [coumarin-p11950775] Identification of the cytochromes P450 that catalyze coumarin 3,4-epoxidation and 3-hydroxylation. (2002). https://pubmed.ncbi.nlm.nih.gov/11950775/ DOI: 10.1124/dmd.30.5.483

evidence_span

{"source_cache": "artifacts/coumarin-research/15665333.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "79f42118f337ffe818b92138941685126173355131f8e12ca7cae9a437800a5b", "start_char": 0, "end_char": 1689, "text_sha256": "79f42118f337ffe818b92138941685126173355131f8e12ca7cae9a437800a5b"}

experimental_model

Purified human CYP2A6 kinetic experiments

exposure

Coumarin oxidation; stopped-flow and steady-state kinetics, selected measures at 23 C

limitations

Biochemical rates do not measure whole-body clearance; accessory b5 species is not specified in the abstract.

nutrient_topic

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

organism

Human CYP2A6 with reconstituted accessory proteins

plain_language

CYP2A6 adds an oxygen-containing group to coumarin.

primary_references

[coumarin-p15665333] Kinetic analysis of oxidation of coumarins by human cytochrome P450 2A6. (2005). https://pubmed.ncbi.nlm.nih.gov/15665333/ DOI: 10.1074/jbc.m411019200

tissue_or_cell_type

Reconstituted enzyme system

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 137–148

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human CYP2A6 kinetic experiments · source_derived_draft · unverified_draft

### coumarin-2a6-7oh Human CYP2A6 catalyzed conversion of coumarin to 7-hydroxycoumarin. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: CYP2A6 adds an oxygen-containing group to coumarin. organism: Human CYP2A6 with reconstituted accessory proteins tissue_or_cell_type: Reconstituted enzyme system experimental_model: Purified human CYP2A6 kinetic experiments limitations: Biochemical rates do not measure whole-body clearance; accessory b5 species is not specified in the abstract. exposure: Coumarin oxidation; stopped-flow and steady-state kinetics, selected measures at 23 C evidence_span: {"source_cache": "artifacts/coumarin-research/15665333.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "79f42118f337ffe818b92138941685126173355131f8e12ca7cae9a437800a5b", "start_char": 0, "end_char": 1689, "text_sha256": "79f42118f337ffe818b92138941685126173355131f8e12ca7cae9a437800a5b"} [coumarin-p15665333] Kinetic analysis of oxidation of coumarins by human cytochrome P450 2A6. (2005). https://pubmed.ncbi.nlm.nih.gov/15665333/ DOI: 10.1074/jbc.m411019200

evidence_span

{"source_cache": "artifacts/coumarin-research/11950775.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "98a03fafa68ef4d55593a3b725af646175a11b42ce02b1dfe02be84ff49d4861", "start_char": 0, "end_char": 1158, "text_sha256": "98a03fafa68ef4d55593a3b725af646175a11b42ce02b1dfe02be84ff49d4861"}

experimental_model

Recombinant CYP enzymes, immunoinhibition and mouse lung inhibitor experiments

exposure

CYP1A/2E antibody inhibition and 5-phenyl-pentyne lung experiments

limitations

Relative contributions depend on species and tissue; this is not a clinical drug-interaction study.

nutrient_topic

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

organism

Human, rat and mouse; each claim specifies enzyme origin

plain_language

CYP2E1 also produces the reactive intermediate.

primary_references

[coumarin-p11950775] Identification of the cytochromes P450 that catalyze coumarin 3,4-epoxidation and 3-hydroxylation. (2002). https://pubmed.ncbi.nlm.nih.gov/11950775/ DOI: 10.1124/dmd.30.5.483

tissue_or_cell_type

Liver and lung microsomes

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 241–252

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant CYP enzymes, immunoinhibition and mouse lung inhibitor experiments · source_derived_draft · unverified_draft

### coumarin-2e1-epoxide Recombinant human CYP2E1 catalyzed coumarin 3,4-epoxide formation. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: CYP2E1 also produces the reactive intermediate. organism: Human, rat and mouse; each claim specifies enzyme origin tissue_or_cell_type: Liver and lung microsomes experimental_model: Recombinant CYP enzymes, immunoinhibition and mouse lung inhibitor experiments limitations: Relative contributions depend on species and tissue; this is not a clinical drug-interaction study. exposure: CYP1A/2E antibody inhibition and 5-phenyl-pentyne lung experiments evidence_span: {"source_cache": "artifacts/coumarin-research/11950775.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "98a03fafa68ef4d55593a3b725af646175a11b42ce02b1dfe02be84ff49d4861", "start_char": 0, "end_char": 1158, "text_sha256": "98a03fafa68ef4d55593a3b725af646175a11b42ce02b1dfe02be84ff49d4861"} [coumarin-p11950775] Identification of the cytochromes P450 that catalyze coumarin 3,4-epoxidation and 3-hydroxylation. (2002). https://pubmed.ncbi.nlm.nih.gov/11950775/ DOI: 10.1124/dmd.30.5.483

evidence_span

{"source_cache": "artifacts/coumarin-research/11950775.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "98a03fafa68ef4d55593a3b725af646175a11b42ce02b1dfe02be84ff49d4861", "start_char": 0, "end_char": 1158, "text_sha256": "98a03fafa68ef4d55593a3b725af646175a11b42ce02b1dfe02be84ff49d4861"}

experimental_model

Recombinant CYP enzymes, immunoinhibition and mouse lung inhibitor experiments

exposure

CYP1A/2E antibody inhibition and 5-phenyl-pentyne lung experiments

limitations

Relative contributions depend on species and tissue; this is not a clinical drug-interaction study.

nutrient_topic

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

organism

Human, rat and mouse; each claim specifies enzyme origin

plain_language

3-Hydroxycoumarin is not treated as the epoxide itself.

primary_references

[coumarin-p11950775] Identification of the cytochromes P450 that catalyze coumarin 3,4-epoxidation and 3-hydroxylation. (2002). https://pubmed.ncbi.nlm.nih.gov/11950775/ DOI: 10.1124/dmd.30.5.483

tissue_or_cell_type

Liver and lung microsomes

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 267–278

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant CYP enzymes, immunoinhibition and mouse lung inhibitor experiments · source_derived_draft · unverified_draft

### coumarin-3oh-separate CYP3A and CYP1A forms supported minor 3-hydroxylation, experimentally distinct from the epoxide pathway. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: 3-Hydroxycoumarin is not treated as the epoxide itself. organism: Human, rat and mouse; each claim specifies enzyme origin tissue_or_cell_type: Liver and lung microsomes experimental_model: Recombinant CYP enzymes, immunoinhibition and mouse lung inhibitor experiments limitations: Relative contributions depend on species and tissue; this is not a clinical drug-interaction study. exposure: CYP1A/2E antibody inhibition and 5-phenyl-pentyne lung experiments evidence_span: {"source_cache": "artifacts/coumarin-research/11950775.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "98a03fafa68ef4d55593a3b725af646175a11b42ce02b1dfe02be84ff49d4861", "start_char": 0, "end_char": 1158, "text_sha256": "98a03fafa68ef4d55593a3b725af646175a11b42ce02b1dfe02be84ff49d4861"} [coumarin-p11950775] Identification of the cytochromes P450 that catalyze coumarin 3,4-epoxidation and 3-hydroxylation. (2002). https://pubmed.ncbi.nlm.nih.gov/11950775/ DOI: 10.1124/dmd.30.5.483

evidence_span

{"source_cache": "artifacts/coumarin-research/15665333.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "79f42118f337ffe818b92138941685126173355131f8e12ca7cae9a437800a5b", "start_char": 0, "end_char": 1689, "text_sha256": "79f42118f337ffe818b92138941685126173355131f8e12ca7cae9a437800a5b"}

experimental_model

Purified human CYP2A6 kinetic experiments

exposure

Coumarin oxidation; stopped-flow and steady-state kinetics, selected measures at 23 C

limitations

Biochemical rates do not measure whole-body clearance; accessory b5 species is not specified in the abstract.

nutrient_topic

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

organism

Human CYP2A6 with reconstituted accessory proteins

plain_language

An accessory electron carrier improved the enzyme reaction.

primary_references

[coumarin-p15665333] Kinetic analysis of oxidation of coumarins by human cytochrome P450 2A6. (2005). https://pubmed.ncbi.nlm.nih.gov/15665333/ DOI: 10.1074/jbc.m411019200

tissue_or_cell_type

Reconstituted enzyme system

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 150–161

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human CYP2A6 kinetic experiments · source_derived_draft · unverified_draft

### coumarin-b5-enhancement Cytochrome b5 increased CYP2A6-mediated coumarin hydroxylation; kinetic experiments supported electron transfer to the oxygenated enzyme. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: An accessory electron carrier improved the enzyme reaction. organism: Human CYP2A6 with reconstituted accessory proteins tissue_or_cell_type: Reconstituted enzyme system experimental_model: Purified human CYP2A6 kinetic experiments limitations: Biochemical rates do not measure whole-body clearance; accessory b5 species is not specified in the abstract. exposure: Coumarin oxidation; stopped-flow and steady-state kinetics, selected measures at 23 C evidence_span: {"source_cache": "artifacts/coumarin-research/15665333.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "79f42118f337ffe818b92138941685126173355131f8e12ca7cae9a437800a5b", "start_char": 0, "end_char": 1689, "text_sha256": "79f42118f337ffe818b92138941685126173355131f8e12ca7cae9a437800a5b"} [coumarin-p15665333] Kinetic analysis of oxidation of coumarins by human cytochrome P450 2A6. (2005). https://pubmed.ncbi.nlm.nih.gov/15665333/ DOI: 10.1074/jbc.m411019200

evidence_span

{"source_cache": "artifacts/coumarin-research/11950775.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "98a03fafa68ef4d55593a3b725af646175a11b42ce02b1dfe02be84ff49d4861", "start_char": 0, "end_char": 1158, "text_sha256": "98a03fafa68ef4d55593a3b725af646175a11b42ce02b1dfe02be84ff49d4861"}

experimental_model

Recombinant CYP enzymes, immunoinhibition and mouse lung inhibitor experiments

exposure

CYP1A/2E antibody inhibition and 5-phenyl-pentyne lung experiments

limitations

Relative contributions depend on species and tissue; this is not a clinical drug-interaction study.

nutrient_topic

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

organism

Human, rat and mouse; each claim specifies enzyme origin

plain_language

Mouse lung has a tissue-specific activation route.

primary_references

[coumarin-p11950775] Identification of the cytochromes P450 that catalyze coumarin 3,4-epoxidation and 3-hydroxylation. (2002). https://pubmed.ncbi.nlm.nih.gov/11950775/ DOI: 10.1124/dmd.30.5.483

tissue_or_cell_type

Liver and lung microsomes

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 254–265

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant CYP enzymes, immunoinhibition and mouse lung inhibitor experiments · source_derived_draft · unverified_draft

### coumarin-mouse-lung-epoxide Inhibitor experiments attributed up to 67% of whole-mouse-lung microsomal epoxidation to CYP2F2. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Mouse lung has a tissue-specific activation route. organism: Human, rat and mouse; each claim specifies enzyme origin tissue_or_cell_type: Liver and lung microsomes experimental_model: Recombinant CYP enzymes, immunoinhibition and mouse lung inhibitor experiments limitations: Relative contributions depend on species and tissue; this is not a clinical drug-interaction study. exposure: CYP1A/2E antibody inhibition and 5-phenyl-pentyne lung experiments evidence_span: {"source_cache": "artifacts/coumarin-research/11950775.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "98a03fafa68ef4d55593a3b725af646175a11b42ce02b1dfe02be84ff49d4861", "start_char": 0, "end_char": 1158, "text_sha256": "98a03fafa68ef4d55593a3b725af646175a11b42ce02b1dfe02be84ff49d4861"} [coumarin-p11950775] Identification of the cytochromes P450 that catalyze coumarin 3,4-epoxidation and 3-hydroxylation. (2002). https://pubmed.ncbi.nlm.nih.gov/11950775/ DOI: 10.1124/dmd.30.5.483