Nutrient chapter

Coumarin

Coumarin. Species, exposure and limitations are retained in each linked claim.

66 recorded mechanisms · 2 availability situations · 8 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

What the sources say this nutrient does, one relationship at a time. Plain wording comes first; the technical statement follows.

The study explicitly distinguished parent 1,2-benzopyrone from anticoagulant coumarin derivatives.
Coumarin → Classification as a vitamin K antagonist anticoagulant source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Human CYP2A6 catalyzed conversion of coumarin to 7-hydroxycoumarin.
Human cytochrome P450 2A6 / CYP2A6 → 7-Hydroxycoumarin / umbelliferone source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Coumarin 3,4-epoxide can rearrange spontaneously to the reactive aldehyde o-HPA.
Coumarin 3,4-epoxide → ortho-Hydroxyphenylacetaldehyde source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/coumarin-research/15141102.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2ddbcb7b41520d3405b9abe3ed8b492c5a6063e88d52c549481d444dcd541dc5", "start_char": 0, "end_char": 2618, "text_sha256": "2ddbcb7b41520d3405b9abe3ed8b492c5a6063e88d52c549481d444dcd541dc5"}
experimental_model
Coumarin epoxide generated with mouse microsomes plus species-specific liver cytosols
exposure
Controlled epoxide generation with cofactors supplied
limitations
Cell-free species comparison does not quantify human dietary injury risk or supplement benefit.
nutrient_topic
Coumarin research collection; topical membership is not evidence of a direct dietary effect. · Coumarin
organism
Human pooled cytosols, F344 rat and B6C3F1 mouse
plain_language
The short-lived epoxide can become an aldehyde.
primary_references
[coumarin-p15141102] Metabolic detoxification determines species differences in coumarin-induced hepatotoxicity. (2004). https://pubmed.ncbi.nlm.nih.gov/15141102/ DOI: 10.1093/toxsci/kfh162
tissue_or_cell_type
Liver cytosolic detoxification system
Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 475–486
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Coumarin epoxide generated with mouse microsomes plus species-specific liver cytosols · source_derived_draft · unverified_draft
### coumarin-epoxide-rearrangement Coumarin 3,4-epoxide can rearrange spontaneously to the reactive aldehyde o-HPA. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The short-lived epoxide can become an aldehyde. organism: Human pooled cytosols, F344 rat and B6C3F1 mouse tissue_or_cell_type: Liver cytosolic detoxification system experimental_model: Coumarin epoxide generated with mouse microsomes plus species-specific liver cytosols limitations: Cell-free species comparison does not quantify human dietary injury risk or supplement benefit. exposure: Controlled epoxide generation with cofactors supplied evidence_span: {"source_cache": "artifacts/coumarin-research/15141102.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2ddbcb7b41520d3405b9abe3ed8b492c5a6063e88d52c549481d444dcd541dc5", "start_char": 0, "end_char": 2618, "text_sha256": "2ddbcb7b41520d3405b9abe3ed8b492c5a6063e88d52c549481d444dcd541dc5"} [coumarin-p15141102] Metabolic detoxification determines species differences in coumarin-induced hepatotoxicity. (2004). https://pubmed.ncbi.nlm.nih.gov/15141102/ DOI: 10.1093/toxsci/kfh162
Complete structured claim and evidence
Rat and mouse cytosols conjugated the epoxide with glutathione through enzymatic and nonenzymatic routes.
Rat and mouse hepatic glutathione S-transferase preparations in the 2004 coumarin study → Coumarin 3,4-epoxide glutathione conjugate source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/coumarin-research/15141102.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2ddbcb7b41520d3405b9abe3ed8b492c5a6063e88d52c549481d444dcd541dc5", "start_char": 0, "end_char": 2618, "text_sha256": "2ddbcb7b41520d3405b9abe3ed8b492c5a6063e88d52c549481d444dcd541dc5"}
experimental_model
Coumarin epoxide generated with mouse microsomes plus species-specific liver cytosols
exposure
Controlled epoxide generation with cofactors supplied
limitations
Cell-free species comparison does not quantify human dietary injury risk or supplement benefit.
nutrient_topic
Coumarin research collection; topical membership is not evidence of a direct dietary effect. · Coumarin
organism
Human pooled cytosols, F344 rat and B6C3F1 mouse
plain_language
Glutathione captures the epoxide in the rodent preparations.
primary_references
[coumarin-p15141102] Metabolic detoxification determines species differences in coumarin-induced hepatotoxicity. (2004). https://pubmed.ncbi.nlm.nih.gov/15141102/ DOI: 10.1093/toxsci/kfh162
tissue_or_cell_type
Liver cytosolic detoxification system
Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 488–499
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Coumarin epoxide generated with mouse microsomes plus species-specific liver cytosols · source_derived_draft · unverified_draft
### coumarin-gst-conjugation Rat and mouse cytosols conjugated the epoxide with glutathione through enzymatic and nonenzymatic routes. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione captures the epoxide in the rodent preparations. organism: Human pooled cytosols, F344 rat and B6C3F1 mouse tissue_or_cell_type: Liver cytosolic detoxification system experimental_model: Coumarin epoxide generated with mouse microsomes plus species-specific liver cytosols limitations: Cell-free species comparison does not quantify human dietary injury risk or supplement benefit. exposure: Controlled epoxide generation with cofactors supplied evidence_span: {"source_cache": "artifacts/coumarin-research/15141102.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2ddbcb7b41520d3405b9abe3ed8b492c5a6063e88d52c549481d444dcd541dc5", "start_char": 0, "end_char": 2618, "text_sha256": "2ddbcb7b41520d3405b9abe3ed8b492c5a6063e88d52c549481d444dcd541dc5"} [coumarin-p15141102] Metabolic detoxification determines species differences in coumarin-induced hepatotoxicity. (2004). https://pubmed.ncbi.nlm.nih.gov/15141102/ DOI: 10.1093/toxsci/kfh162
Complete structured claim and evidence
Pooled human liver cytosols oxidized o-HPA to o-HPAA, with intrinsic clearance over 50-fold greater than rat cytosols.
Human liver cytosolic o-HPA oxidation; enzyme isoform unresolved → ortho-Hydroxyphenylacetic acid source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/coumarin-research/15141102.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2ddbcb7b41520d3405b9abe3ed8b492c5a6063e88d52c549481d444dcd541dc5", "start_char": 0, "end_char": 2618, "text_sha256": "2ddbcb7b41520d3405b9abe3ed8b492c5a6063e88d52c549481d444dcd541dc5"}
experimental_model
Coumarin epoxide generated with mouse microsomes plus species-specific liver cytosols
exposure
Controlled epoxide generation with cofactors supplied
limitations
Cell-free species comparison does not quantify human dietary injury risk or supplement benefit.
nutrient_topic
Coumarin research collection; topical membership is not evidence of a direct dietary effect. · Coumarin
organism
Human pooled cytosols, F344 rat and B6C3F1 mouse
plain_language
Human and rat preparations cleared the aldehyde at very different rates.
primary_references
[coumarin-p15141102] Metabolic detoxification determines species differences in coumarin-induced hepatotoxicity. (2004). https://pubmed.ncbi.nlm.nih.gov/15141102/ DOI: 10.1093/toxsci/kfh162
tissue_or_cell_type
Liver cytosolic detoxification system
Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 501–512
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Coumarin epoxide generated with mouse microsomes plus species-specific liver cytosols · source_derived_draft · unverified_draft
### coumarin-human-aldehyde-oxidation Pooled human liver cytosols oxidized o-HPA to o-HPAA, with intrinsic clearance over 50-fold greater than rat cytosols. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Human and rat preparations cleared the aldehyde at very different rates. organism: Human pooled cytosols, F344 rat and B6C3F1 mouse tissue_or_cell_type: Liver cytosolic detoxification system experimental_model: Coumarin epoxide generated with mouse microsomes plus species-specific liver cytosols limitations: Cell-free species comparison does not quantify human dietary injury risk or supplement benefit. exposure: Controlled epoxide generation with cofactors supplied evidence_span: {"source_cache": "artifacts/coumarin-research/15141102.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2ddbcb7b41520d3405b9abe3ed8b492c5a6063e88d52c549481d444dcd541dc5", "start_char": 0, "end_char": 2618, "text_sha256": "2ddbcb7b41520d3405b9abe3ed8b492c5a6063e88d52c549481d444dcd541dc5"} [coumarin-p15141102] Metabolic detoxification determines species differences in coumarin-induced hepatotoxicity. (2004). https://pubmed.ncbi.nlm.nih.gov/15141102/ DOI: 10.1093/toxsci/kfh162
Complete structured claim and evidence
CYP2A6 variant alleles were identified in individuals with poor coumarin metabolism, including a single-amino-acid inactivating variant.
CYP2A6 variant alleles in the 1995 coumarin phenotyping study; original nomenclature retained → Coumarin 7-hydroxylation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/coumarin-research/7668294.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "aeb377e6bbda1a552066c5d1caf1bf558753096627b863835637a0f2f942b3b1", "start_char": 0, "end_char": 1316, "text_sha256": "aeb377e6bbda1a552066c5d1caf1bf558753096627b863835637a0f2f942b3b1"}
experimental_model
CYP2A gene sequencing and coumarin metabolic phenotyping
exposure
Original CYP2A6v1/v2 nomenclature; poor-metabolizer individuals
limitations
Historical variant labels retained; no automatic mapping to modern star alleles and no demonstrated prediction of liver injury.
nutrient_topic
Coumarin research collection; topical membership is not evidence of a direct dietary effect. · Coumarin
organism
Human
plain_language
Inherited enzyme differences can change how coumarin is processed.
primary_references
[coumarin-p7668294] A genetic polymorphism in coumarin 7-hydroxylation: sequence of the human CYP2A genes and identification of variant CYP2A6 alleles. (1995). https://pubmed.ncbi.nlm.nih.gov/7668294/
tissue_or_cell_type
Genomic DNA and whole-body probe metabolism
trigger_kind
machinery_impairment Imported condition classification; unverified.
Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 631–642
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CYP2A gene sequencing and coumarin metabolic phenotyping · source_derived_draft · unverified_draft
### coumarin-genetic-variation CYP2A6 variant alleles were identified in individuals with poor coumarin metabolism, including a single-amino-acid inactivating variant. Condition category: machinery_impairment nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Inherited enzyme differences can change how coumarin is processed. organism: Human tissue_or_cell_type: Genomic DNA and whole-body probe metabolism experimental_model: CYP2A gene sequencing and coumarin metabolic phenotyping limitations: Historical variant labels retained; no automatic mapping to modern star alleles and no demonstrated prediction of liver injury. exposure: Original CYP2A6v1/v2 nomenclature; poor-metabolizer individuals evidence_span: {"source_cache": "artifacts/coumarin-research/7668294.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "aeb377e6bbda1a552066c5d1caf1bf558753096627b863835637a0f2f942b3b1", "start_char": 0, "end_char": 1316, "text_sha256": "aeb377e6bbda1a552066c5d1caf1bf558753096627b863835637a0f2f942b3b1"} [coumarin-p7668294] A genetic polymorphism in coumarin 7-hydroxylation: sequence of the human CYP2A genes and identification of variant CYP2A6 alleles. (1995). https://pubmed.ncbi.nlm.nih.gov/7668294/
Complete structured claim and evidence
The 1993 trial reported arm edema declining from 46% to 26% above normal during active treatment (P<0.001).
Coumarin → Arm volume in human lymphedema source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
At six months arm volume changed by +58 mL on coumarin versus +21 mL on placebo (P=0.80).
Coumarin → Arm volume in human lymphedema source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Serologic liver toxicity occurred in 6% of women during the coumarin trial.
Coumarin → Serologic liver toxicity during coumarin treatment source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Cytochrome b5 increased CYP2A6-mediated coumarin hydroxylation; kinetic experiments supported electron transfer to the oxygenated enzyme.
Cytochrome b5 preparation used in the 2005 CYP2A6 kinetic experiment; species not resolved in abstract → Coumarin 7-hydroxylation source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
CYP2A6 Asn297 hydrogen bonding oriented coumarin within a compact hydrophobic active site for position-selective oxidation.
Human cytochrome P450 2A6 / CYP2A6 → Coumarin source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Methoxsalen filled the CYP2A6 active-site cavity without substantially changing the protein structure.
Methoxsalen / 8-methoxypsoralen → Human cytochrome P450 2A6 / CYP2A6 source_derived_draftungraded
Experimental context and source evidence
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
This distinct compound fits into the same enzyme pocket.
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 176–187
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-methoxsalen-binding Methoxsalen filled the CYP2A6 active-site cavity without substantially changing the protein structure. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This distinct compound fits into the same enzyme pocket. 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
Complete structured claim and evidence
Mean 7-hydroxycoumarin formation was 1230 of 1420 pmol/min/mg total polar products in the 12-sample human microsomal panel.
Coumarin → 7-Hydroxycoumarin / umbelliferone source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Coumarin-derived material bound covalently to human microsomal proteins, averaging 4.8 pmol/min/mg.
Coumarin → Coumarin-derived covalent binding to human liver microsomal proteins source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Recombinant human CYP1A enzymes catalyzed coumarin epoxidation; CYP1A1 was among the tested human forms.
Human cytochrome P450 1A1 → Coumarin 3,4-epoxide source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Recombinant human CYP1A2 catalyzed coumarin 3,4-epoxide formation.
Human cytochrome P450 1A2 → Coumarin 3,4-epoxide source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Recombinant human CYP2E1 catalyzed coumarin 3,4-epoxide formation.
Human cytochrome P450 2E1 → Coumarin 3,4-epoxide source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Inhibitor experiments attributed up to 67% of whole-mouse-lung microsomal epoxidation to CYP2F2.
Mouse cytochrome P450 2F2 → Coumarin 3,4-epoxide source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
CYP3A and CYP1A forms supported minor 3-hydroxylation, experimentally distinct from the epoxide pathway.
CYP3A preparations in the 2002 coumarin metabolism study; species-specific scope in claims → 3-Hydroxycoumarin source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
The coumarin epoxide glutathione conjugate was isolated and structurally characterized, with glutathione attached at position 3.
Coumarin 3,4-epoxide → Coumarin 3,4-epoxide glutathione conjugate source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/coumarin-research/12954377.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3cfcf94368e2f91bed45cd7901678e6db02567ac1c8e7d8b8c78bae52932d76f", "start_char": 0, "end_char": 1196, "text_sha256": "3cfcf94368e2f91bed45cd7901678e6db02567ac1c8e7d8b8c78bae52932d76f"}
experimental_model
HPLC isolation with mass spectrometry and NMR characterization
exposure
Purification of coumarin epoxide glutathione conjugate
limitations
Analytical identification does not establish protection by oral glutathione.
nutrient_topic
Coumarin research collection; topical membership is not evidence of a direct dietary effect. · Coumarin
organism
Hepatic microsomal preparations; species detailed in original paper
plain_language
Glutathione can become chemically attached to this reactive metabolite.
primary_references
[coumarin-p12954377] Liquid chromatographic determination of the glutathione conjugate and ring-opened metabolites formed from coumarin epoxidation. (2003). https://pubmed.ncbi.nlm.nih.gov/12954377/ DOI: 10.1016/s1570-0232(03)00473-2
tissue_or_cell_type
In vitro metabolism mixtures
Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 280–291
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · HPLC isolation with mass spectrometry and NMR characterization · source_derived_draft · unverified_draft
### coumarin-conjugate-identity The coumarin epoxide glutathione conjugate was isolated and structurally characterized, with glutathione attached at position 3. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione can become chemically attached to this reactive metabolite. organism: Hepatic microsomal preparations; species detailed in original paper tissue_or_cell_type: In vitro metabolism mixtures experimental_model: HPLC isolation with mass spectrometry and NMR characterization limitations: Analytical identification does not establish protection by oral glutathione. exposure: Purification of coumarin epoxide glutathione conjugate evidence_span: {"source_cache": "artifacts/coumarin-research/12954377.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3cfcf94368e2f91bed45cd7901678e6db02567ac1c8e7d8b8c78bae52932d76f", "start_char": 0, "end_char": 1196, "text_sha256": "3cfcf94368e2f91bed45cd7901678e6db02567ac1c8e7d8b8c78bae52932d76f"} [coumarin-p12954377] Liquid chromatographic determination of the glutathione conjugate and ring-opened metabolites formed from coumarin epoxidation. (2003). https://pubmed.ncbi.nlm.nih.gov/12954377/ DOI: 10.1016/s1570-0232(03)00473-2
Complete structured claim and evidence
Coumarin accelerated tissue protein removal relative to nonmetabolizable PVP in rat edema models; enhanced proteolysis was proposed.
Coumarin → Rat edematous-tissue protein clearance source_derived_draftungraded
Experimental context and source evidence
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/
Complete structured claim and evidence
Coumarin increased macrophage morphologies interpreted as recruitment and elicited activity in canine lymphedema.
Coumarin → Macrophage morphological recruitment/activation indices in canine lymphedema source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Coumarin induced G0/G1 arrest in HeLa cells.
Coumarin → G0/G1 arrest in human HeLa cells source_derived_draftungraded
Experimental context and source evidence
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/
Complete structured claim and evidence
Coumarin dose-dependently reduced HeLa mitochondrial membrane potential.
Coumarin → Mitochondrial depolarization in HeLa cells source_derived_draftungraded
Experimental context and source evidence
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/
Complete structured claim and evidence
Coumarin reduced BCL2 expression in HeLa cells.
Coumarin → Human BCL2 source_derived_draftungraded
Experimental context and source evidence
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/
Complete structured claim and evidence
Coumarin reduced Bcl-xL expression in HeLa cells.
Coumarin → Human BCL2L1 / Bcl-xL isoform specified in claim source_derived_draftungraded
Experimental context and source evidence
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/
Complete structured claim and evidence
Coumarin increased BAX expression in HeLa cells.
Coumarin → Human BAX source_derived_draftungraded
Experimental context and source evidence
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/
Complete structured claim and evidence
Coumarin promoted cytochrome c release from HeLa mitochondria.
Coumarin → Mitochondrial cytochrome c release in HeLa cells source_derived_draftungraded
Experimental context and source evidence
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/
Complete structured claim and evidence
Coumarin activated caspase-3 in HeLa cells before apoptosis.
Coumarin → Human caspase-3 / CASP3 source_derived_draftungraded
Experimental context and source evidence
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/
Complete structured claim and evidence
Coumarin inhibited proliferation reversibly after drug removal in the tested malignant cell panel.
Coumarin → Proliferation of study-specified human malignant cell lines source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
7-Hydroxycoumarin also produced dose- and time-dependent reversible growth inhibition.
7-Hydroxycoumarin / umbelliferone → Proliferation of study-specified human malignant cell lines source_derived_draftungraded
Experimental context and source evidence
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 metabolite had its own measured activity.
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 423–434
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-metabolite-cytostasis 7-Hydroxycoumarin also produced dose- and time-dependent reversible growth inhibition. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The metabolite had its own measured activity. 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
Complete structured claim and evidence
Coumarin stimulated apoptosis in HL-60, but not the other cell lines tested in this study.
Coumarin → Apoptosis in human HL-60 cells source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Coumarin inhibited proliferation with IC50 values of 1.59–3.57 mM across this four-cell-line panel.
Coumarin → Proliferation of study-specified human malignant cell lines source_derived_draftungraded
Experimental context and source evidence
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/
Complete structured claim and evidence
The 7-hydroxycoumarin glucuronide was ineffective in the proliferation assays where parent and unconjugated metabolite were active.
7-Hydroxycoumarin glucuronide → Proliferation of study-specified human malignant cell lines source_derived_draftungraded
Experimental context and source evidence
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
Conjugation changed the measured biological effect.
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 462–473
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-glucuronide-null The 7-hydroxycoumarin glucuronide was ineffective in the proliferation assays where parent and unconjugated metabolite were active. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Conjugation changed the measured biological effect. 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/
Complete structured claim and evidence
With cofactors supplied, human cytosolic products were approximately 90% o-HPAA and 10% glutathione conjugate.
Coumarin 3,4-epoxide → ortho-Hydroxyphenylacetic acid source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/coumarin-research/15141102.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2ddbcb7b41520d3405b9abe3ed8b492c5a6063e88d52c549481d444dcd541dc5", "start_char": 0, "end_char": 2618, "text_sha256": "2ddbcb7b41520d3405b9abe3ed8b492c5a6063e88d52c549481d444dcd541dc5"}
experimental_model
Coumarin epoxide generated with mouse microsomes plus species-specific liver cytosols
exposure
Controlled epoxide generation with cofactors supplied
limitations
Cell-free species comparison does not quantify human dietary injury risk or supplement benefit.
nutrient_topic
Coumarin research collection; topical membership is not evidence of a direct dietary effect. · Coumarin
organism
Human pooled cytosols, F344 rat and B6C3F1 mouse
plain_language
Glutathione capture was not the dominant measured human route.
primary_references
[coumarin-p15141102] Metabolic detoxification determines species differences in coumarin-induced hepatotoxicity. (2004). https://pubmed.ncbi.nlm.nih.gov/15141102/ DOI: 10.1093/toxsci/kfh162
tissue_or_cell_type
Liver cytosolic detoxification system
Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 514–525
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Coumarin epoxide generated with mouse microsomes plus species-specific liver cytosols · source_derived_draft · unverified_draft
### coumarin-human-route-partition With cofactors supplied, human cytosolic products were approximately 90% o-HPAA and 10% glutathione conjugate. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione capture was not the dominant measured human route. organism: Human pooled cytosols, F344 rat and B6C3F1 mouse tissue_or_cell_type: Liver cytosolic detoxification system experimental_model: Coumarin epoxide generated with mouse microsomes plus species-specific liver cytosols limitations: Cell-free species comparison does not quantify human dietary injury risk or supplement benefit. exposure: Controlled epoxide generation with cofactors supplied evidence_span: {"source_cache": "artifacts/coumarin-research/15141102.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2ddbcb7b41520d3405b9abe3ed8b492c5a6063e88d52c549481d444dcd541dc5", "start_char": 0, "end_char": 2618, "text_sha256": "2ddbcb7b41520d3405b9abe3ed8b492c5a6063e88d52c549481d444dcd541dc5"} [coumarin-p15141102] Metabolic detoxification determines species differences in coumarin-induced hepatotoxicity. (2004). https://pubmed.ncbi.nlm.nih.gov/15141102/ DOI: 10.1093/toxsci/kfh162
Complete structured claim and evidence
All three species reduced o-HPA to o-HPE; this was a major reaction only in rat preparations.
ortho-Hydroxyphenylacetaldehyde → ortho-Hydroxyphenylethanol source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/coumarin-research/15141102.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2ddbcb7b41520d3405b9abe3ed8b492c5a6063e88d52c549481d444dcd541dc5", "start_char": 0, "end_char": 2618, "text_sha256": "2ddbcb7b41520d3405b9abe3ed8b492c5a6063e88d52c549481d444dcd541dc5"}
experimental_model
Coumarin epoxide generated with mouse microsomes plus species-specific liver cytosols
exposure
Controlled epoxide generation with cofactors supplied
limitations
Cell-free species comparison does not quantify human dietary injury risk or supplement benefit.
nutrient_topic
Coumarin research collection; topical membership is not evidence of a direct dietary effect. · Coumarin
organism
Human pooled cytosols, F344 rat and B6C3F1 mouse
plain_language
Reduction provides another disposal branch, with species differences.
primary_references
[coumarin-p15141102] Metabolic detoxification determines species differences in coumarin-induced hepatotoxicity. (2004). https://pubmed.ncbi.nlm.nih.gov/15141102/ DOI: 10.1093/toxsci/kfh162
tissue_or_cell_type
Liver cytosolic detoxification system
Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 527–538
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Coumarin epoxide generated with mouse microsomes plus species-specific liver cytosols · source_derived_draft · unverified_draft
### coumarin-aldehyde-reduction All three species reduced o-HPA to o-HPE; this was a major reaction only in rat preparations. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Reduction provides another disposal branch, with species differences. organism: Human pooled cytosols, F344 rat and B6C3F1 mouse tissue_or_cell_type: Liver cytosolic detoxification system experimental_model: Coumarin epoxide generated with mouse microsomes plus species-specific liver cytosols limitations: Cell-free species comparison does not quantify human dietary injury risk or supplement benefit. exposure: Controlled epoxide generation with cofactors supplied evidence_span: {"source_cache": "artifacts/coumarin-research/15141102.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2ddbcb7b41520d3405b9abe3ed8b492c5a6063e88d52c549481d444dcd541dc5", "start_char": 0, "end_char": 2618, "text_sha256": "2ddbcb7b41520d3405b9abe3ed8b492c5a6063e88d52c549481d444dcd541dc5"} [coumarin-p15141102] Metabolic detoxification determines species differences in coumarin-induced hepatotoxicity. (2004). https://pubmed.ncbi.nlm.nih.gov/15141102/ DOI: 10.1093/toxsci/kfh162
Complete structured claim and evidence
Bovine liver UGT preparation converted 7-hydroxycoumarin and UDP-glucuronic acid into its glucuronide.
Bovine liver UDP-glucuronosyltransferase preparation; isoforms unresolved → 7-Hydroxycoumarin glucuronide source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/coumarin-research/8877866.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8092618f6e2773ad94670c810fb44af7c2acedc0680674872af23af8bc55e26d", "start_char": 0, "end_char": 2114, "text_sha256": "8092618f6e2773ad94670c810fb44af7c2acedc0680674872af23af8bc55e26d"}
experimental_model
Enzyme assay and HPLC metabolite identification
exposure
7-Hydroxycoumarin plus UDP-glucuronic acid
limitations
Bovine preparation does not identify a dominant human UGT isoform.
nutrient_topic
Coumarin research collection; topical membership is not evidence of a direct dietary effect. · Coumarin
organism
Bovine
plain_language
A sugar-acid donor enables the conjugation step.
primary_references
[coumarin-p8877866] Analysis of the glucuronidation of 7-hydroxycoumarin by HPLC. (1996). https://pubmed.ncbi.nlm.nih.gov/8877866/ DOI: 10.1016/0731-7085(96)01801-8
tissue_or_cell_type
Liver homogenate/crude UGT preparation
Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 540–551
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Enzyme assay and HPLC metabolite identification · source_derived_draft · unverified_draft
### coumarin-ugt-conjugation Bovine liver UGT preparation converted 7-hydroxycoumarin and UDP-glucuronic acid into its glucuronide. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A sugar-acid donor enables the conjugation step. organism: Bovine tissue_or_cell_type: Liver homogenate/crude UGT preparation experimental_model: Enzyme assay and HPLC metabolite identification limitations: Bovine preparation does not identify a dominant human UGT isoform. exposure: 7-Hydroxycoumarin plus UDP-glucuronic acid evidence_span: {"source_cache": "artifacts/coumarin-research/8877866.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8092618f6e2773ad94670c810fb44af7c2acedc0680674872af23af8bc55e26d", "start_char": 0, "end_char": 2114, "text_sha256": "8092618f6e2773ad94670c810fb44af7c2acedc0680674872af23af8bc55e26d"} [coumarin-p8877866] Analysis of the glucuronidation of 7-hydroxycoumarin by HPLC. (1996). https://pubmed.ncbi.nlm.nih.gov/8877866/ DOI: 10.1016/0731-7085(96)01801-8
Complete structured claim and evidence
Methoxsalen produced mechanism-based CYP2A6 inhibition, with reported inactivation rate 0.5/min.
Methoxsalen / 8-methoxypsoralen → Human cytochrome P450 2A6 / CYP2A6 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/coumarin-research/9143352.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dca3f4253c2977d47070bb95696634ee2e06fa9a28a3d76ac9790ce695ed6f09", "start_char": 0, "end_char": 2723, "text_sha256": "dca3f4253c2977d47070bb95696634ee2e06fa9a28a3d76ac9790ce695ed6f09"}
experimental_model
Human microsomal and recombinant CYP2A6 inhibitor screen
exposure
Coumarin 0.5–50 micromolar; 47 inhibitor/substrate probes
limitations
In vitro inhibition thresholds are not demonstrated clinical interactions at food exposure.
nutrient_topic
Coumarin research collection; topical membership is not evidence of a direct dietary effect. · Coumarin
organism
Human
plain_language
Methoxsalen can disable this enzyme during metabolism.
primary_references
[coumarin-p9143352] Inhibition of coumarin 7-hydroxylase activity in human liver microsomes. (1997). https://pubmed.ncbi.nlm.nih.gov/9143352/ DOI: 10.1006/abbi.1997.9964
tissue_or_cell_type
Liver enzyme preparations
Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 553–564
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human microsomal and recombinant CYP2A6 inhibitor screen · source_derived_draft · unverified_draft
### coumarin-methoxsalen-inactivation Methoxsalen produced mechanism-based CYP2A6 inhibition, with reported inactivation rate 0.5/min. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Methoxsalen can disable this enzyme during metabolism. organism: Human tissue_or_cell_type: Liver enzyme preparations experimental_model: Human microsomal and recombinant CYP2A6 inhibitor screen limitations: In vitro inhibition thresholds are not demonstrated clinical interactions at food exposure. exposure: Coumarin 0.5–50 micromolar; 47 inhibitor/substrate probes evidence_span: {"source_cache": "artifacts/coumarin-research/9143352.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dca3f4253c2977d47070bb95696634ee2e06fa9a28a3d76ac9790ce695ed6f09", "start_char": 0, "end_char": 2723, "text_sha256": "dca3f4253c2977d47070bb95696634ee2e06fa9a28a3d76ac9790ce695ed6f09"} [coumarin-p9143352] Inhibition of coumarin 7-hydroxylase activity in human liver microsomes. (1997). https://pubmed.ncbi.nlm.nih.gov/9143352/ DOI: 10.1006/abbi.1997.9964
Complete structured claim and evidence
Tranylcypromine competitively inhibited coumarin 7-hydroxylation, with Ki 0.04 micromolar.
Tranylcypromine → Coumarin 7-hydroxylation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/coumarin-research/9143352.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dca3f4253c2977d47070bb95696634ee2e06fa9a28a3d76ac9790ce695ed6f09", "start_char": 0, "end_char": 2723, "text_sha256": "dca3f4253c2977d47070bb95696634ee2e06fa9a28a3d76ac9790ce695ed6f09"}
experimental_model
Human microsomal and recombinant CYP2A6 inhibitor screen
exposure
Coumarin 0.5–50 micromolar; 47 inhibitor/substrate probes
limitations
In vitro inhibition thresholds are not demonstrated clinical interactions at food exposure.
nutrient_topic
Coumarin research collection; topical membership is not evidence of a direct dietary effect. · Coumarin
organism
Human
plain_language
A medicine inhibited the coumarin-processing reaction in vitro.
primary_references
[coumarin-p9143352] Inhibition of coumarin 7-hydroxylase activity in human liver microsomes. (1997). https://pubmed.ncbi.nlm.nih.gov/9143352/ DOI: 10.1006/abbi.1997.9964
tissue_or_cell_type
Liver enzyme preparations
Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 566–577
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human microsomal and recombinant CYP2A6 inhibitor screen · source_derived_draft · unverified_draft
### coumarin-tranylcypromine-inhibition Tranylcypromine competitively inhibited coumarin 7-hydroxylation, with Ki 0.04 micromolar. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A medicine inhibited the coumarin-processing reaction in vitro. organism: Human tissue_or_cell_type: Liver enzyme preparations experimental_model: Human microsomal and recombinant CYP2A6 inhibitor screen limitations: In vitro inhibition thresholds are not demonstrated clinical interactions at food exposure. exposure: Coumarin 0.5–50 micromolar; 47 inhibitor/substrate probes evidence_span: {"source_cache": "artifacts/coumarin-research/9143352.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dca3f4253c2977d47070bb95696634ee2e06fa9a28a3d76ac9790ce695ed6f09", "start_char": 0, "end_char": 2723, "text_sha256": "dca3f4253c2977d47070bb95696634ee2e06fa9a28a3d76ac9790ce695ed6f09"} [coumarin-p9143352] Inhibition of coumarin 7-hydroxylase activity in human liver microsomes. (1997). https://pubmed.ncbi.nlm.nih.gov/9143352/ DOI: 10.1006/abbi.1997.9964
Complete structured claim and evidence
Nicotine inhibited CYP2A6 coumarin hydroxylation within the study inhibitor category of Ki below 200 micromolar.
Nicotine → Coumarin 7-hydroxylation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/coumarin-research/9143352.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dca3f4253c2977d47070bb95696634ee2e06fa9a28a3d76ac9790ce695ed6f09", "start_char": 0, "end_char": 2723, "text_sha256": "dca3f4253c2977d47070bb95696634ee2e06fa9a28a3d76ac9790ce695ed6f09"}
experimental_model
Human microsomal and recombinant CYP2A6 inhibitor screen
exposure
Coumarin 0.5–50 micromolar; 47 inhibitor/substrate probes
limitations
In vitro inhibition thresholds are not demonstrated clinical interactions at food exposure.
nutrient_topic
Coumarin research collection; topical membership is not evidence of a direct dietary effect. · Coumarin
organism
Human
plain_language
Nicotine and coumarin can interact in an enzyme assay.
primary_references
[coumarin-p9143352] Inhibition of coumarin 7-hydroxylase activity in human liver microsomes. (1997). https://pubmed.ncbi.nlm.nih.gov/9143352/ DOI: 10.1006/abbi.1997.9964
tissue_or_cell_type
Liver enzyme preparations
Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 579–590
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human microsomal and recombinant CYP2A6 inhibitor screen · source_derived_draft · unverified_draft
### coumarin-nicotine-inhibition Nicotine inhibited CYP2A6 coumarin hydroxylation within the study inhibitor category of Ki below 200 micromolar. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Nicotine and coumarin can interact in an enzyme assay. organism: Human tissue_or_cell_type: Liver enzyme preparations experimental_model: Human microsomal and recombinant CYP2A6 inhibitor screen limitations: In vitro inhibition thresholds are not demonstrated clinical interactions at food exposure. exposure: Coumarin 0.5–50 micromolar; 47 inhibitor/substrate probes evidence_span: {"source_cache": "artifacts/coumarin-research/9143352.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dca3f4253c2977d47070bb95696634ee2e06fa9a28a3d76ac9790ce695ed6f09", "start_char": 0, "end_char": 2723, "text_sha256": "dca3f4253c2977d47070bb95696634ee2e06fa9a28a3d76ac9790ce695ed6f09"} [coumarin-p9143352] Inhibition of coumarin 7-hydroxylase activity in human liver microsomes. (1997). https://pubmed.ncbi.nlm.nih.gov/9143352/ DOI: 10.1006/abbi.1997.9964
Complete structured claim and evidence
Warfarin showed little or no CYP2A6 inhibition in this assay, with Ki above 200 micromolar.
Warfarin → Coumarin 7-hydroxylation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/coumarin-research/9143352.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dca3f4253c2977d47070bb95696634ee2e06fa9a28a3d76ac9790ce695ed6f09", "start_char": 0, "end_char": 2723, "text_sha256": "dca3f4253c2977d47070bb95696634ee2e06fa9a28a3d76ac9790ce695ed6f09"}
experimental_model
Human microsomal and recombinant CYP2A6 inhibitor screen
exposure
Coumarin 0.5–50 micromolar; 47 inhibitor/substrate probes
limitations
In vitro inhibition thresholds are not demonstrated clinical interactions at food exposure.
nutrient_topic
Coumarin research collection; topical membership is not evidence of a direct dietary effect. · Coumarin
organism
Human
plain_language
Warfarin is a separate molecule with a different principal target.
primary_references
[coumarin-p9143352] Inhibition of coumarin 7-hydroxylase activity in human liver microsomes. (1997). https://pubmed.ncbi.nlm.nih.gov/9143352/ DOI: 10.1006/abbi.1997.9964
tissue_or_cell_type
Liver enzyme preparations
Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 592–603
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human microsomal and recombinant CYP2A6 inhibitor screen · source_derived_draft · unverified_draft
### coumarin-warfarin-inhibition-null Warfarin showed little or no CYP2A6 inhibition in this assay, with Ki above 200 micromolar. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Warfarin is a separate molecule with a different principal target. organism: Human tissue_or_cell_type: Liver enzyme preparations experimental_model: Human microsomal and recombinant CYP2A6 inhibitor screen limitations: In vitro inhibition thresholds are not demonstrated clinical interactions at food exposure. exposure: Coumarin 0.5–50 micromolar; 47 inhibitor/substrate probes evidence_span: {"source_cache": "artifacts/coumarin-research/9143352.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dca3f4253c2977d47070bb95696634ee2e06fa9a28a3d76ac9790ce695ed6f09", "start_char": 0, "end_char": 2723, "text_sha256": "dca3f4253c2977d47070bb95696634ee2e06fa9a28a3d76ac9790ce695ed6f09"} [coumarin-p9143352] Inhibition of coumarin 7-hydroxylase activity in human liver microsomes. (1997). https://pubmed.ncbi.nlm.nih.gov/9143352/ DOI: 10.1006/abbi.1997.9964
Complete structured claim and evidence
CYP2A6 K476E had lower affinity for NADPH-P450 reductase, contributing to reduced catalytic activity.
Human CYP2A6 K476E experimental variant → NADPH-cytochrome P450 oxidoreductase / POR source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/coumarin-research/16207711.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a5f0bef9ac62d55ff5725e8c5cb4eca3e76ef715c758654e76c0c596c52ceab7", "start_char": 0, "end_char": 1740, "text_sha256": "a5f0bef9ac62d55ff5725e8c5cb4eca3e76ef715c758654e76c0c596c52ceab7"}
experimental_model
Random mutagenesis of recombinant human CYP2A6
exposure
Wild-type enzyme and selected activity-reducing mutants
limitations
Engineered protein dysfunction is not nutrient deficiency; no rescue by nutritional supplementation was tested.
nutrient_topic
Coumarin research collection; topical membership is not evidence of a direct dietary effect. · Coumarin
organism
Human engineered protein
plain_language
A protein change weakened its connection to the electron donor.
primary_references
[coumarin-p16207711] Analysis of coumarin 7-hydroxylation activity of cytochrome P450 2A6 using random mutagenesis. (2005). https://pubmed.ncbi.nlm.nih.gov/16207711/ DOI: 10.1074/jbc.m508171200
tissue_or_cell_type
Reconstituted enzyme system
trigger_kind
machinery_impairment Imported condition classification; unverified.
Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 605–616
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Random mutagenesis of recombinant human CYP2A6 · source_derived_draft · unverified_draft
### coumarin-k476e-por CYP2A6 K476E had lower affinity for NADPH-P450 reductase, contributing to reduced catalytic activity. Condition category: machinery_impairment nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A protein change weakened its connection to the electron donor. organism: Human engineered protein tissue_or_cell_type: Reconstituted enzyme system experimental_model: Random mutagenesis of recombinant human CYP2A6 limitations: Engineered protein dysfunction is not nutrient deficiency; no rescue by nutritional supplementation was tested. exposure: Wild-type enzyme and selected activity-reducing mutants evidence_span: {"source_cache": "artifacts/coumarin-research/16207711.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a5f0bef9ac62d55ff5725e8c5cb4eca3e76ef715c758654e76c0c596c52ceab7", "start_char": 0, "end_char": 1740, "text_sha256": "a5f0bef9ac62d55ff5725e8c5cb4eca3e76ef715c758654e76c0c596c52ceab7"} [coumarin-p16207711] Analysis of coumarin 7-hydroxylation activity of cytochrome P450 2A6 using random mutagenesis. (2005). https://pubmed.ncbi.nlm.nih.gov/16207711/ DOI: 10.1074/jbc.m508171200
Complete structured claim and evidence
K476E reduced NADPH oxidation and ferric-enzyme reduction; excess reductase did not restore wild-type coumarin hydroxylation.
Human CYP2A6 K476E experimental variant → Coumarin 7-hydroxylation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/coumarin-research/16207711.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a5f0bef9ac62d55ff5725e8c5cb4eca3e76ef715c758654e76c0c596c52ceab7", "start_char": 0, "end_char": 1740, "text_sha256": "a5f0bef9ac62d55ff5725e8c5cb4eca3e76ef715c758654e76c0c596c52ceab7"}
experimental_model
Random mutagenesis of recombinant human CYP2A6
exposure
Wild-type enzyme and selected activity-reducing mutants
limitations
Engineered protein dysfunction is not nutrient deficiency; no rescue by nutritional supplementation was tested.
nutrient_topic
Coumarin research collection; topical membership is not evidence of a direct dietary effect. · Coumarin
organism
Human engineered protein
plain_language
Adding more partner enzyme did not fully repair this variant.
primary_references
[coumarin-p16207711] Analysis of coumarin 7-hydroxylation activity of cytochrome P450 2A6 using random mutagenesis. (2005). https://pubmed.ncbi.nlm.nih.gov/16207711/ DOI: 10.1074/jbc.m508171200
tissue_or_cell_type
Reconstituted enzyme system
trigger_kind
machinery_impairment Imported condition classification; unverified.
Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 618–629
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Random mutagenesis of recombinant human CYP2A6 · source_derived_draft · unverified_draft
### coumarin-k476e-hydroxylation K476E reduced NADPH oxidation and ferric-enzyme reduction; excess reductase did not restore wild-type coumarin hydroxylation. Condition category: machinery_impairment nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Adding more partner enzyme did not fully repair this variant. organism: Human engineered protein tissue_or_cell_type: Reconstituted enzyme system experimental_model: Random mutagenesis of recombinant human CYP2A6 limitations: Engineered protein dysfunction is not nutrient deficiency; no rescue by nutritional supplementation was tested. exposure: Wild-type enzyme and selected activity-reducing mutants evidence_span: {"source_cache": "artifacts/coumarin-research/16207711.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a5f0bef9ac62d55ff5725e8c5cb4eca3e76ef715c758654e76c0c596c52ceab7", "start_char": 0, "end_char": 1740, "text_sha256": "a5f0bef9ac62d55ff5725e8c5cb4eca3e76ef715c758654e76c0c596c52ceab7"} [coumarin-p16207711] Analysis of coumarin 7-hydroxylation activity of cytochrome P450 2A6 using random mutagenesis. (2005). https://pubmed.ncbi.nlm.nih.gov/16207711/ DOI: 10.1074/jbc.m508171200
Complete structured claim and evidence
Approximately 1% of orally administered coumarin reached systemic circulation unchanged in this pilot study.
Coumarin → Systemic exposure to unchanged coumarin source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
7-Hydroxycoumarin glucuronide was measured after oral coumarin, supporting extensive absorption and first-pass metabolism.
Coumarin → 7-Hydroxycoumarin glucuronide source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Isolated coumarin capsules produced 62.8% mean urinary 7-hydroxycoumarin recovery over eight hours.
Coumarin → Urinary recovery of coumarin-derived 7-hydroxycoumarin source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Cinnamon-powder capsules produced 56.0% mean urinary metabolite recovery.
Cinnamon powder capsule delivering 12 mg coumarin in the 2011 crossover study → Urinary recovery of coumarin-derived 7-hydroxycoumarin source_derived_draftungraded
Experimental context and source evidence
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
The cinnamon matrix still allowed substantial absorption.
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 683–694
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-cinnamon-capsule-recovery Cinnamon-powder capsules produced 56.0% mean urinary metabolite recovery. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cinnamon matrix still allowed substantial absorption. 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
Complete structured claim and evidence
Cinnamon tea produced 66.1% mean urinary recovery and the highest early plasma metabolite peaks.
Cinnamon tea delivering 12 mg coumarin in the 2011 crossover study → Urinary recovery of coumarin-derived 7-hydroxycoumarin source_derived_draftungraded
Experimental context and source evidence
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
The tea formulation was absorbed rapidly.
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 696–707
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-tea-recovery Cinnamon tea produced 66.1% mean urinary recovery and the highest early plasma metabolite peaks. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The tea formulation was absorbed rapidly. 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
Complete structured claim and evidence
Cinnamon rice pudding produced 54.7% mean urinary metabolite recovery.
Cinnamon rice pudding delivering 12 mg coumarin in the 2011 crossover study → Urinary recovery of coumarin-derived 7-hydroxycoumarin source_derived_draftungraded
Experimental context and source evidence
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
A food matrix did not prevent coumarin uptake.
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 709–720
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-pudding-recovery Cinnamon rice pudding produced 54.7% mean urinary metabolite recovery. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A food matrix did not prevent coumarin uptake. 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
Complete structured claim and evidence
Leg edema declined from 25% to 17% above normal in the 1993 trial (P<0.001).
Coumarin → Leg volume in human lymphedema source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Moderate/large reported benefit occurred in 15% on coumarin versus 10% on placebo (P=0.19).
Coumarin → Patient-reported lymphedema symptoms source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Crystallography and extracted-flavin analysis identified FAD bound to recombinant human POR.
NADPH-cytochrome P450 oxidoreductase / POR → FAD source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Primary Results, wild-type structure and cofactor-binding sites; Methods flavin extraction/HPLC.
experimental_model
Human POR structure and flavin-content analysis
exposure
Recombinant N-terminally truncated human POR; X-ray structure and HPLC flavin assays.
limitations
The structural study did not measure vitamin D outcomes after riboflavin dosing; linkage to CYP2R1 comes from the separate direct reconstitution record.
nutrient
Vitamin D2 and D3 · Vitamin D2 and D3
nutrient_topic
Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3
organism
Homo sapiens protein
plain_language
POR carries a FAD cofactor derived from vitamin B2.
primary_references
[xia2011] Structural basis for human NADPH-cytochrome P450 oxidoreductase deficiency. (2011). https://pubmed.ncbi.nlm.nih.gov/21808038/ DOI: 10.1073/pnas.1106632108
tissue_or_cell_type
POR cofactor-binding domain
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 407–420
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human POR structure and flavin-content analysis · source_derived_draft · unverified_draft
### vd-act-por-fad Crystallography and extracted-flavin analysis identified FAD bound to recombinant human POR. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: POR carries a FAD cofactor derived from vitamin B2. organism: Homo sapiens protein tissue_or_cell_type: POR cofactor-binding domain experimental_model: Human POR structure and flavin-content analysis limitations: The structural study did not measure vitamin D outcomes after riboflavin dosing; linkage to CYP2R1 comes from the separate direct reconstitution record. exposure: Recombinant N-terminally truncated human POR; X-ray structure and HPLC flavin assays. cross_nutrient: true evidence_location: Primary Results, wild-type structure and cofactor-binding sites; Methods flavin extraction/HPLC. nutrient: Vitamin D2 and D3 [xia2011] Structural basis for human NADPH-cytochrome P450 oxidoreductase deficiency. (2011). https://pubmed.ncbi.nlm.nih.gov/21808038/ DOI: 10.1073/pnas.1106632108
Complete structured claim and evidence
Crystallography and extracted-flavin analysis identified FMN bound to recombinant human POR.
NADPH-cytochrome P450 oxidoreductase / POR → Flavin mononucleotide source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Primary Results, wild-type structure and cofactor-binding sites; Methods flavin extraction/HPLC.
experimental_model
Human POR structure and flavin-content analysis
exposure
Recombinant N-terminally truncated human POR; X-ray structure and HPLC flavin assays.
limitations
The structural study did not measure vitamin D outcomes after riboflavin dosing; linkage to CYP2R1 comes from the separate direct reconstitution record.
nutrient
Vitamin D2 and D3 · Vitamin D2 and D3
nutrient_topic
Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3
organism
Homo sapiens protein
plain_language
POR carries a FMN cofactor derived from vitamin B2.
primary_references
[xia2011] Structural basis for human NADPH-cytochrome P450 oxidoreductase deficiency. (2011). https://pubmed.ncbi.nlm.nih.gov/21808038/ DOI: 10.1073/pnas.1106632108
tissue_or_cell_type
POR cofactor-binding domain
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 422–435
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human POR structure and flavin-content analysis · source_derived_draft · unverified_draft
### vd-act-por-fmn Crystallography and extracted-flavin analysis identified FMN bound to recombinant human POR. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: POR carries a FMN cofactor derived from vitamin B2. organism: Homo sapiens protein tissue_or_cell_type: POR cofactor-binding domain experimental_model: Human POR structure and flavin-content analysis limitations: The structural study did not measure vitamin D outcomes after riboflavin dosing; linkage to CYP2R1 comes from the separate direct reconstitution record. exposure: Recombinant N-terminally truncated human POR; X-ray structure and HPLC flavin assays. cross_nutrient: true evidence_location: Primary Results, wild-type structure and cofactor-binding sites; Methods flavin extraction/HPLC. nutrient: Vitamin D2 and D3 [xia2011] Structural basis for human NADPH-cytochrome P450 oxidoreductase deficiency. (2011). https://pubmed.ncbi.nlm.nih.gov/21808038/ DOI: 10.1073/pnas.1106632108
Complete structured claim and evidence
Human RFK phosphorylates riboflavin to FMN using ATP, yielding ADP; this precedes FLAD1-mediated FAD synthesis.
Riboflavin kinase / RFK → Riboflavin (vitamin B2) source_derived_draftungraded
Experimental context and source evidence
evidence_location
Abstract and product-bound structure
experimental_model
Human RFK structural and catalytic mechanism study
exposure
Purified RFK with flavin and adenine nucleotide ligands.
limitations
Reaction chemistry does not imply RFK controls every tissue flavin pool to the same extent.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
RFK performs the first activation step from riboflavin to FMN.
primary_references
[transport-rfk-2003] Ligand binding-induced conformational changes in riboflavin kinase: structural basis for the ordered mechanism. (2003). https://pubmed.ncbi.nlm.nih.gov/14580199/ DOI: 10.1021/bi035450t
tissue_or_cell_type
Purified protein
Riboflavin: mechanisms, deficiency and nutrient interactions (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 · Human RFK structural and catalytic mechanism study · source_derived_draft · unverified_draft
### transport-rfk-phosphorylation Human RFK phosphorylates riboflavin to FMN using ATP, yielding ADP; this precedes FLAD1-mediated FAD synthesis. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: RFK performs the first activation step from riboflavin to FMN. organism: Homo sapiens tissue_or_cell_type: Purified protein experimental_model: Human RFK structural and catalytic mechanism study limitations: Reaction chemistry does not imply RFK controls every tissue flavin pool to the same extent. exposure: Purified RFK with flavin and adenine nucleotide ligands. evidence_location: Abstract and product-bound structure [transport-rfk-2003] Ligand binding-induced conformational changes in riboflavin kinase: structural basis for the ordered mechanism. (2003). https://pubmed.ncbi.nlm.nih.gov/14580199/ DOI: 10.1021/bi035450t
Complete structured claim and evidence
Human G6PD uses glucose-6-phosphate and catalytic NADP+ to generate NADPH.
Glucose-6-phosphate dehydrogenase / G6PD → NADPH source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/35858355.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "02c2d0e880b17ab304fab0854064813ffec5fa9e647b978a083aa88fbf8a38f0", "start_char": 0, "end_char": 1328, "text_sha256": "02c2d0e880b17ab304fab0854064813ffec5fa9e647b978a083aa88fbf8a38f0"}
experimental_model
Cryo-EM and structural comparison
exposure
Ligand-free and NADP/G6P-bound states
limitations
Structural NADP and catalytic NADP are different sites; enzyme activity is not a niacin-treatment trial.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human
plain_language
The reducing power used in glutathione recycling has to be replenished.
primary_references
[glutathione-p35858355] Allosteric role of a structural NADP+ molecule in glucose-6-phosphate dehydrogenase activity. (2022). https://pubmed.ncbi.nlm.nih.gov/35858355/ DOI: 10.1073/pnas.2119695119
tissue_or_cell_type
Purified wild-type G6PD and D200N
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 762–773
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-EM and structural comparison · source_derived_draft · unverified_draft
### glutathione-g6pd-nadph Human G6PD uses glucose-6-phosphate and catalytic NADP+ to generate NADPH. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The reducing power used in glutathione recycling has to be replenished. organism: Human tissue_or_cell_type: Purified wild-type G6PD and D200N experimental_model: Cryo-EM and structural comparison limitations: Structural NADP and catalytic NADP are different sites; enzyme activity is not a niacin-treatment trial. exposure: Ligand-free and NADP/G6P-bound states evidence_span: {"source_cache": "artifacts/glutathione-research/35858355.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "02c2d0e880b17ab304fab0854064813ffec5fa9e647b978a083aa88fbf8a38f0", "start_char": 0, "end_char": 1328, "text_sha256": "02c2d0e880b17ab304fab0854064813ffec5fa9e647b978a083aa88fbf8a38f0"} [glutathione-p35858355] Allosteric role of a structural NADP+ molecule in glucose-6-phosphate dehydrogenase activity. (2022). https://pubmed.ncbi.nlm.nih.gov/35858355/ DOI: 10.1073/pnas.2119695119
Complete structured claim and evidence
Authenticated C. verum bark contained only trace coumarin, whereas the tested cassia-type species contained substantial amounts.
Ceylon cinnamon / Cinnamomum verum bark preparations → Coumarin source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Cinnamaldehyde inhibited recombinant human CYP2A6, with reported IC50 6.1 micromolar; inhibition increased with time and required NADPH.
trans-Cinnamaldehyde / cinnamal → Human cytochrome P450 2A6 / CYP2A6 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ceylon-research/26851241.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c2fb6b18a3ba708f060d53011ea0e198f98fe980930297e714c488a41413b5a2", "start_char": 0, "end_char": 1591, "text_sha256": "c2fb6b18a3ba708f060d53011ea0e198f98fe980930297e714c488a41413b5a2"}
experimental_model
Recombinant human CYP assays and mechanistic static modeling
exposure
Cinnamaldehyde, NADPH and glutathione; modeled inhibitor concentrations 0.1 and 1 micromolar
limitations
Enzyme inhibition and model predictions are not measured clinical drug interactions. NADPH omission is not dietary niacin deficiency.
nutrient_topic
Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect. · Ceylon cinnamon / Cinnamomum verum bark preparations
organism
Human enzyme preparations; computational model
plain_language
The chemical interfered with a drug-metabolizing enzyme when its catalytic system was operating.
primary_references
[ceylon-p26851241] Inactivation of CYP2A6 by the Dietary Phenylpropanoid trans-Cinnamic Aldehyde (Cinnamaldehyde) and Estimation of Interactions with Nicotine and Letrozole. (2016). https://pubmed.ncbi.nlm.nih.gov/26851241/ DOI: 10.1124/dmd.115.067942
tissue_or_cell_type
CYP2A6 reaction system
Ceylon cinnamon: metabolism, signaling and nutrient connections (2026-09-17) · lines 727–738
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human CYP assays and mechanistic static modeling · source_derived_draft · unverified_draft
### ceylon-cyp2a6 Cinnamaldehyde inhibited recombinant human CYP2A6, with reported IC50 6.1 micromolar; inhibition increased with time and required NADPH. Condition category: normal nutrient_topic: Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect. plain_language: The chemical interfered with a drug-metabolizing enzyme when its catalytic system was operating. organism: Human enzyme preparations; computational model tissue_or_cell_type: CYP2A6 reaction system experimental_model: Recombinant human CYP assays and mechanistic static modeling limitations: Enzyme inhibition and model predictions are not measured clinical drug interactions. NADPH omission is not dietary niacin deficiency. exposure: Cinnamaldehyde, NADPH and glutathione; modeled inhibitor concentrations 0.1 and 1 micromolar evidence_span: {"source_cache": "artifacts/ceylon-research/26851241.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c2fb6b18a3ba708f060d53011ea0e198f98fe980930297e714c488a41413b5a2", "start_char": 0, "end_char": 1591, "text_sha256": "c2fb6b18a3ba708f060d53011ea0e198f98fe980930297e714c488a41413b5a2"} [ceylon-p26851241] Inactivation of CYP2A6 by the Dietary Phenylpropanoid trans-Cinnamic Aldehyde (Cinnamaldehyde) and Estimation of Interactions with Nicotine and Letrozole. (2016). https://pubmed.ncbi.nlm.nih.gov/26851241/ DOI: 10.1124/dmd.115.067942
Complete structured claim and evidence
Mass spectra indicated cinnamaldehyde-associated CYP2A6 apoprotein adduction, with reported mass addition about 132.67 Da; added glutathione did not prevent this measured adduction.
trans-Cinnamaldehyde / cinnamal → Cinnamaldehyde-associated CYP2A6 apoprotein mass adduction source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ceylon-research/32788161.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "431169f83241cb83b84dd81d84eb1db225735677cabf33f09af8b1e22dfe64f4", "start_char": 0, "end_char": 2507, "text_sha256": "431169f83241cb83b84dd81d84eb1db225735677cabf33f09af8b1e22dfe64f4"}
experimental_model
CYP2A6 mass spectrometry, time-dependent inhibition and numerical modeling
exposure
Cinnamaldehyde and separately 2-methoxycinnamaldehyde; model exposure approximately 275 mg cinnamaldehyde
limitations
Rat-scaled predicted human AUC is not observed AUC. Heme loss was specifically reported for the methoxy analogue; apoprotein adduction is a different endpoint from inhibition.
nutrient_topic
Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect. · Ceylon cinnamon / Cinnamomum verum bark preparations
organism
Human CYP2A6; rat-scaled modeling parameters
plain_language
The protein acquired extra mass even with glutathione present. This differs from measuring how much enzyme activity survives.
primary_references
[ceylon-p32788161] Mechanisms of Herb-Drug Interactions Involving Cinnamon and CYP2A6: Focus on Time-Dependent Inhibition by Cinnamaldehyde and 2-Methoxycinnamaldehyde. (2020). https://pubmed.ncbi.nlm.nih.gov/32788161/ DOI: 10.1124/dmd.120.000087
tissue_or_cell_type
Enzyme apoprotein/heme; simulated drug exposure
Ceylon cinnamon: metabolism, signaling and nutrient connections (2026-09-17) · lines 766–777
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CYP2A6 mass spectrometry, time-dependent inhibition and numerical modeling · source_derived_draft · unverified_draft
### ceylon-cyp-adduct Mass spectra indicated cinnamaldehyde-associated CYP2A6 apoprotein adduction, with reported mass addition about 132.67 Da; added glutathione did not prevent this measured adduction. Condition category: normal nutrient_topic: Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect. plain_language: The protein acquired extra mass even with glutathione present. This differs from measuring how much enzyme activity survives. organism: Human CYP2A6; rat-scaled modeling parameters tissue_or_cell_type: Enzyme apoprotein/heme; simulated drug exposure experimental_model: CYP2A6 mass spectrometry, time-dependent inhibition and numerical modeling limitations: Rat-scaled predicted human AUC is not observed AUC. Heme loss was specifically reported for the methoxy analogue; apoprotein adduction is a different endpoint from inhibition. exposure: Cinnamaldehyde and separately 2-methoxycinnamaldehyde; model exposure approximately 275 mg cinnamaldehyde evidence_span: {"source_cache": "artifacts/ceylon-research/32788161.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "431169f83241cb83b84dd81d84eb1db225735677cabf33f09af8b1e22dfe64f4", "start_char": 0, "end_char": 2507, "text_sha256": "431169f83241cb83b84dd81d84eb1db225735677cabf33f09af8b1e22dfe64f4"} [ceylon-p32788161] Mechanisms of Herb-Drug Interactions Involving Cinnamon and CYP2A6: Focus on Time-Dependent Inhibition by Cinnamaldehyde and 2-Methoxycinnamaldehyde. (2020). https://pubmed.ncbi.nlm.nih.gov/32788161/ DOI: 10.1124/dmd.120.000087
Complete structured claim and evidence
Added glutathione modestly but significantly reduced the extent of cinnamaldehyde-dependent CYP2A6 inhibition.
GSH → Human cytochrome P450 2A6 / CYP2A6 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ceylon-research/26851241.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c2fb6b18a3ba708f060d53011ea0e198f98fe980930297e714c488a41413b5a2", "start_char": 0, "end_char": 1591, "text_sha256": "c2fb6b18a3ba708f060d53011ea0e198f98fe980930297e714c488a41413b5a2"}
experimental_model
Recombinant human CYP assays and mechanistic static modeling
exposure
Cinnamaldehyde, NADPH and glutathione; modeled inhibitor concentrations 0.1 and 1 micromolar
limitations
Enzyme inhibition and model predictions are not measured clinical drug interactions. NADPH omission is not dietary niacin deficiency.
nutrient_topic
Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect. · Ceylon cinnamon / Cinnamomum verum bark preparations
organism
Human enzyme preparations; computational model
plain_language
Glutathione partially buffered this enzyme effect in the assay; supplement protection was not tested.
primary_references
[ceylon-p26851241] Inactivation of CYP2A6 by the Dietary Phenylpropanoid trans-Cinnamic Aldehyde (Cinnamaldehyde) and Estimation of Interactions with Nicotine and Letrozole. (2016). https://pubmed.ncbi.nlm.nih.gov/26851241/ DOI: 10.1124/dmd.115.067942
tissue_or_cell_type
CYP2A6 reaction system
Ceylon cinnamon: metabolism, signaling and nutrient connections (2026-09-17) · lines 740–751
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human CYP assays and mechanistic static modeling · source_derived_draft · unverified_draft
### ceylon-gsh-cyp Added glutathione modestly but significantly reduced the extent of cinnamaldehyde-dependent CYP2A6 inhibition. Condition category: normal nutrient_topic: Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione partially buffered this enzyme effect in the assay; supplement protection was not tested. organism: Human enzyme preparations; computational model tissue_or_cell_type: CYP2A6 reaction system experimental_model: Recombinant human CYP assays and mechanistic static modeling limitations: Enzyme inhibition and model predictions are not measured clinical drug interactions. NADPH omission is not dietary niacin deficiency. exposure: Cinnamaldehyde, NADPH and glutathione; modeled inhibitor concentrations 0.1 and 1 micromolar evidence_span: {"source_cache": "artifacts/ceylon-research/26851241.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c2fb6b18a3ba708f060d53011ea0e198f98fe980930297e714c488a41413b5a2", "start_char": 0, "end_char": 1591, "text_sha256": "c2fb6b18a3ba708f060d53011ea0e198f98fe980930297e714c488a41413b5a2"} [ceylon-p26851241] Inactivation of CYP2A6 by the Dietary Phenylpropanoid trans-Cinnamic Aldehyde (Cinnamaldehyde) and Estimation of Interactions with Nicotine and Letrozole. (2016). https://pubmed.ncbi.nlm.nih.gov/26851241/ DOI: 10.1124/dmd.115.067942
Complete structured claim and evidence
Cinnamaldehyde-dependent time-dependent inhibition of CYP2A6 required NADPH in the reconstituted assay.
NADPH → Human cytochrome P450 2A6 / CYP2A6 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/ceylon-research/26851241.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c2fb6b18a3ba708f060d53011ea0e198f98fe980930297e714c488a41413b5a2", "start_char": 0, "end_char": 1591, "text_sha256": "c2fb6b18a3ba708f060d53011ea0e198f98fe980930297e714c488a41413b5a2"}
experimental_model
Recombinant human CYP assays and mechanistic static modeling
exposure
Cinnamaldehyde, NADPH and glutathione; modeled inhibitor concentrations 0.1 and 1 micromolar
limitations
Enzyme inhibition and model predictions are not measured clinical drug interactions. NADPH omission is not dietary niacin deficiency.
nutrient_topic
Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect. · Ceylon cinnamon / Cinnamomum verum bark preparations
organism
Human enzyme preparations; computational model
plain_language
The enzyme had to receive reducing power for this inactivation process to develop.
primary_references
[ceylon-p26851241] Inactivation of CYP2A6 by the Dietary Phenylpropanoid trans-Cinnamic Aldehyde (Cinnamaldehyde) and Estimation of Interactions with Nicotine and Letrozole. (2016). https://pubmed.ncbi.nlm.nih.gov/26851241/ DOI: 10.1124/dmd.115.067942
tissue_or_cell_type
CYP2A6 reaction system
trigger_kind
machinery_impairment Imported condition classification; unverified.
Ceylon cinnamon: metabolism, signaling and nutrient connections (2026-09-17) · lines 753–764
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human CYP assays and mechanistic static modeling · source_derived_draft · unverified_draft
### ceylon-nadph-dependence Cinnamaldehyde-dependent time-dependent inhibition of CYP2A6 required NADPH in the reconstituted assay. Condition category: machinery_impairment nutrient_topic: Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect. plain_language: The enzyme had to receive reducing power for this inactivation process to develop. organism: Human enzyme preparations; computational model tissue_or_cell_type: CYP2A6 reaction system experimental_model: Recombinant human CYP assays and mechanistic static modeling limitations: Enzyme inhibition and model predictions are not measured clinical drug interactions. NADPH omission is not dietary niacin deficiency. exposure: Cinnamaldehyde, NADPH and glutathione; modeled inhibitor concentrations 0.1 and 1 micromolar evidence_span: {"source_cache": "artifacts/ceylon-research/26851241.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c2fb6b18a3ba708f060d53011ea0e198f98fe980930297e714c488a41413b5a2", "start_char": 0, "end_char": 1591, "text_sha256": "c2fb6b18a3ba708f060d53011ea0e198f98fe980930297e714c488a41413b5a2"} [ceylon-p26851241] Inactivation of CYP2A6 by the Dietary Phenylpropanoid trans-Cinnamic Aldehyde (Cinnamaldehyde) and Estimation of Interactions with Nicotine and Letrozole. (2016). https://pubmed.ncbi.nlm.nih.gov/26851241/ DOI: 10.1124/dmd.115.067942
Complete structured claim and evidence
Mangiferin reduced measured CYP2A6 activity in the hepatocyte experiment.
Mangiferin → Human cytochrome P450 2A6 / CYP2A6 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/mangiferin-research/22815239.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e85ebd0af89f030dbeda45ed922e93a8a616c51f5ce1b64badc44d90791716c0", "start_char": 0, "end_char": 1728, "text_sha256": "e85ebd0af89f030dbeda45ed922e93a8a616c51f5ce1b64badc44d90791716c0"}
experimental_model
Primary human hepatocyte exposure
exposure
Mangiferin 50-250 micrograms/mL for 48 hours
limitations
High in vitro concentrations; decreased enzyme activity is not proof of human drug-level changes. Extract and isolated mangiferin are distinct.
nutrient_topic
Mangiferin research collection; topical membership is not evidence of a direct dietary effect. · Mangiferin
organism
Homo sapiens
plain_language
A drug-metabolizing enzyme was inhibited under the tested exposure.
primary_references
[mangiferin-p22815239] Mangifera indica L. extract and mangiferin modulate cytochrome P450 and UDP-glucuronosyltransferase enzymes in primary cultures of human hepatocytes. (2013). https://pubmed.ncbi.nlm.nih.gov/22815239/ DOI: 10.1002/ptr.4782
tissue_or_cell_type
Cultured hepatocytes
Mangiferin: metabolism, signaling and nutrient connections (2026-09-17) · lines 783–794
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary human hepatocyte exposure · source_derived_draft · unverified_draft
### mangiferin-cyp2a6-activity Mangiferin reduced measured CYP2A6 activity in the hepatocyte experiment. Condition category: normal nutrient_topic: Mangiferin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A drug-metabolizing enzyme was inhibited under the tested exposure. organism: Homo sapiens tissue_or_cell_type: Cultured hepatocytes experimental_model: Primary human hepatocyte exposure limitations: High in vitro concentrations; decreased enzyme activity is not proof of human drug-level changes. Extract and isolated mangiferin are distinct. exposure: Mangiferin 50-250 micrograms/mL for 48 hours evidence_span: {"source_cache": "artifacts/mangiferin-research/22815239.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e85ebd0af89f030dbeda45ed922e93a8a616c51f5ce1b64badc44d90791716c0", "start_char": 0, "end_char": 1728, "text_sha256": "e85ebd0af89f030dbeda45ed922e93a8a616c51f5ce1b64badc44d90791716c0"} [mangiferin-p22815239] Mangifera indica L. extract and mangiferin modulate cytochrome P450 and UDP-glucuronosyltransferase enzymes in primary cultures of human hepatocytes. (2013). https://pubmed.ncbi.nlm.nih.gov/22815239/ DOI: 10.1002/ptr.4782
Complete structured claim and evidence
Glutamate-cysteine ligase joins glutamate and cysteine to form gamma-glutamylcysteine in the first glutathione-synthesis step.
Human glutamate-cysteine ligase catalytic subunit / GCLC → Gamma-glutamylcysteine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/sulforaphane-research/30581542.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77cf6674cf9b9bc140a228588a53c937966fd3a67397c1c4970221c5cc58a0b1", "start_char": 762, "end_char": 1092, "text_sha256": "927fa13b085700c20b578ecabc7c8c17a66ea4600b90809e3061d12bcaea3849"}
experimental_model
Human enzyme mutagenesis, kinetics and molecular dynamics
exposure
S-loop variants; established biosynthetic reactions described in the introduction
limitations
Reaction descriptions are background chemistry in a primary enzyme paper, not evidence that sulforaphane corrects inherited GSS deficiency.
nutrient_topic
Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study
organism
Human GSS
plain_language
The induced machinery still needs its amino-acid building blocks.
primary_references
[sulforaphane-p30581542] Genetic Mutations in the S-loop of Human Glutathione Synthetase: Links Between Substrate Binding, Active Site Structure and Allostery. (2019). https://pubmed.ncbi.nlm.nih.gov/30581542/ DOI: 10.1016/j.csbj.2018.11.008
tissue_or_cell_type
Glutathione synthesis and substrate binding
Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 840–851
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human enzyme mutagenesis, kinetics and molecular dynamics · source_derived_draft · unverified_draft
### sulforaphane-gcl-first-step Glutamate-cysteine ligase joins glutamate and cysteine to form gamma-glutamylcysteine in the first glutathione-synthesis step. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: The induced machinery still needs its amino-acid building blocks. organism: Human GSS tissue_or_cell_type: Glutathione synthesis and substrate binding experimental_model: Human enzyme mutagenesis, kinetics and molecular dynamics limitations: Reaction descriptions are background chemistry in a primary enzyme paper, not evidence that sulforaphane corrects inherited GSS deficiency. exposure: S-loop variants; established biosynthetic reactions described in the introduction evidence_span: {"source_cache": "artifacts/sulforaphane-research/30581542.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77cf6674cf9b9bc140a228588a53c937966fd3a67397c1c4970221c5cc58a0b1", "start_char": 762, "end_char": 1092, "text_sha256": "927fa13b085700c20b578ecabc7c8c17a66ea4600b90809e3061d12bcaea3849"} [sulforaphane-p30581542] Genetic Mutations in the S-loop of Human Glutathione Synthetase: Links Between Substrate Binding, Active Site Structure and Allostery. (2019). https://pubmed.ncbi.nlm.nih.gov/30581542/ DOI: 10.1016/j.csbj.2018.11.008
Complete structured claim and evidence
Human GSS joins gamma-glutamylcysteine and glycine in an ATP-dependent reaction to form glutathione.
Human glutathione synthetase / GSS → GSH source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/sulforaphane-research/30581542.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77cf6674cf9b9bc140a228588a53c937966fd3a67397c1c4970221c5cc58a0b1", "start_char": 923, "end_char": 1092, "text_sha256": "bed9ef1323b513b1e31b65277f28b935ddf0c9b0c83cbe9ee9f827f97806846c"}
experimental_model
Human enzyme mutagenesis, kinetics and molecular dynamics
exposure
S-loop variants; established biosynthetic reactions described in the introduction
limitations
Reaction descriptions are background chemistry in a primary enzyme paper, not evidence that sulforaphane corrects inherited GSS deficiency.
nutrient_topic
Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study
organism
Human GSS
plain_language
A second enzyme, glycine and energy complete the molecule.
primary_references
[sulforaphane-p30581542] Genetic Mutations in the S-loop of Human Glutathione Synthetase: Links Between Substrate Binding, Active Site Structure and Allostery. (2019). https://pubmed.ncbi.nlm.nih.gov/30581542/ DOI: 10.1016/j.csbj.2018.11.008
tissue_or_cell_type
Glutathione synthesis and substrate binding
Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 853–864
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human enzyme mutagenesis, kinetics and molecular dynamics · source_derived_draft · unverified_draft
### sulforaphane-gss-second-step Human GSS joins gamma-glutamylcysteine and glycine in an ATP-dependent reaction to form glutathione. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second enzyme, glycine and energy complete the molecule. organism: Human GSS tissue_or_cell_type: Glutathione synthesis and substrate binding experimental_model: Human enzyme mutagenesis, kinetics and molecular dynamics limitations: Reaction descriptions are background chemistry in a primary enzyme paper, not evidence that sulforaphane corrects inherited GSS deficiency. exposure: S-loop variants; established biosynthetic reactions described in the introduction evidence_span: {"source_cache": "artifacts/sulforaphane-research/30581542.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77cf6674cf9b9bc140a228588a53c937966fd3a67397c1c4970221c5cc58a0b1", "start_char": 923, "end_char": 1092, "text_sha256": "bed9ef1323b513b1e31b65277f28b935ddf0c9b0c83cbe9ee9f827f97806846c"} [sulforaphane-p30581542] Genetic Mutations in the S-loop of Human Glutathione Synthetase: Links Between Substrate Binding, Active Site Structure and Allostery. (2019). https://pubmed.ncbi.nlm.nih.gov/30581542/ DOI: 10.1016/j.csbj.2018.11.008
Complete structured claim and evidence
Human GSS crystallized with two magnesium ions, ADP, glutathione and sulfate.
Mg2+ → Human glutathione synthetase / GSS source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/10369661.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ccdd02e451ba6a6d432012c382911ff7fac556e99f9e8d60ce9f3dc94baf9941", "start_char": 0, "end_char": 1327, "text_sha256": "ccdd02e451ba6a6d432012c382911ff7fac556e99f9e8d60ce9f3dc94baf9941"}
experimental_model
Crystal structure and disease-variant mapping
exposure
ADP/GSH/sulfate-bound structure
limitations
Two Mg ions observed; structure is not a dietary-magnesium depletion experiment. The main synthesis reaction is reused from its existing claim.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human enzyme
plain_language
The synthesis enzyme has a metal-containing nucleotide-binding environment.
primary_references
[glutathione-p10369661] Molecular basis of glutathione synthetase deficiency and a rare gene permutation event. (1999). https://pubmed.ncbi.nlm.nih.gov/10369661/ DOI: 10.1093/emboj/18.12.3204
tissue_or_cell_type
Purified GSS
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 333–344
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystal structure and disease-variant mapping · source_derived_draft · unverified_draft
### glutathione-gss-magnesium Human GSS crystallized with two magnesium ions, ADP, glutathione and sulfate. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The synthesis enzyme has a metal-containing nucleotide-binding environment. organism: Human enzyme tissue_or_cell_type: Purified GSS experimental_model: Crystal structure and disease-variant mapping limitations: Two Mg ions observed; structure is not a dietary-magnesium depletion experiment. The main synthesis reaction is reused from its existing claim. exposure: ADP/GSH/sulfate-bound structure evidence_span: {"source_cache": "artifacts/glutathione-research/10369661.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ccdd02e451ba6a6d432012c382911ff7fac556e99f9e8d60ce9f3dc94baf9941", "start_char": 0, "end_char": 1327, "text_sha256": "ccdd02e451ba6a6d432012c382911ff7fac556e99f9e8d60ce9f3dc94baf9941"} [glutathione-p10369661] Molecular basis of glutathione synthetase deficiency and a rare gene permutation event. (1999). https://pubmed.ncbi.nlm.nih.gov/10369661/ DOI: 10.1093/emboj/18.12.3204
Complete structured claim and evidence
Recombinantly expressed VKORC1 activity was sensitive to warfarin.
Warfarin → Human vitamin K epoxide reductase / VKORC1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/14765195.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "32f373fc0363ed079e580b2d47a3cb36c82b46871860fc6740b0285e23936496", "start_char": 0, "end_char": 1385, "text_sha256": "32f373fc0363ed079e580b2d47a3cb36c82b46871860fc6740b0285e23936496"}
experimental_model
siRNA identification and recombinant expression
exposure
Gene silencing, enzyme expression and warfarin sensitivity
limitations
Gene-discovery experiments; later structural understanding supersedes the original minimal topology description.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human VKORC1 and insect-cell expression
plain_language
An anticoagulant acts on cofactor recycling, which changes protein maturation downstream.
primary_references
[k2-p14765195] Identification of the gene for vitamin K epoxide reductase. (2004). https://pubmed.ncbi.nlm.nih.gov/14765195/ DOI: 10.1038/nature02254
tissue_or_cell_type
Vitamin K recycling enzyme
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 448–459
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · siRNA identification and recombinant expression · source_derived_draft · unverified_draft
### k2-warfarin-vkor Recombinantly expressed VKORC1 activity was sensitive to warfarin. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: An anticoagulant acts on cofactor recycling, which changes protein maturation downstream. organism: Human VKORC1 and insect-cell expression tissue_or_cell_type: Vitamin K recycling enzyme experimental_model: siRNA identification and recombinant expression limitations: Gene-discovery experiments; later structural understanding supersedes the original minimal topology description. exposure: Gene silencing, enzyme expression and warfarin sensitivity evidence_span: {"source_cache": "artifacts/k2-research/14765195.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "32f373fc0363ed079e580b2d47a3cb36c82b46871860fc6740b0285e23936496", "start_char": 0, "end_char": 1385, "text_sha256": "32f373fc0363ed079e580b2d47a3cb36c82b46871860fc6740b0285e23936496"} [k2-p14765195] Identification of the gene for vitamin K epoxide reductase. (2004). https://pubmed.ncbi.nlm.nih.gov/14765195/ DOI: 10.1038/nature02254
Complete structured claim and evidence
Silencing the identified VKORC1 gene reduced vitamin K epoxide reductase activity; recombinant expression restored warfarin-sensitive enzyme activity.
Human vitamin K epoxide reductase / VKORC1 → Vitamin K epoxide recycling source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/14765195.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "32f373fc0363ed079e580b2d47a3cb36c82b46871860fc6740b0285e23936496", "start_char": 0, "end_char": 1385, "text_sha256": "32f373fc0363ed079e580b2d47a3cb36c82b46871860fc6740b0285e23936496"}
experimental_model
siRNA identification and recombinant expression
exposure
Gene silencing, enzyme expression and warfarin sensitivity
limitations
Gene-discovery experiments; later structural understanding supersedes the original minimal topology description.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human VKORC1 and insect-cell expression
plain_language
The used vitamin K cofactor can be recycled instead of being replaced after every reaction.
primary_references
[k2-p14765195] Identification of the gene for vitamin K epoxide reductase. (2004). https://pubmed.ncbi.nlm.nih.gov/14765195/ DOI: 10.1038/nature02254
tissue_or_cell_type
Vitamin K recycling enzyme
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 435–446
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · siRNA identification and recombinant expression · source_derived_draft · unverified_draft
### k2-vkor-recycling Silencing the identified VKORC1 gene reduced vitamin K epoxide reductase activity; recombinant expression restored warfarin-sensitive enzyme activity. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The used vitamin K cofactor can be recycled instead of being replaced after every reaction. organism: Human VKORC1 and insect-cell expression tissue_or_cell_type: Vitamin K recycling enzyme experimental_model: siRNA identification and recombinant expression limitations: Gene-discovery experiments; later structural understanding supersedes the original minimal topology description. exposure: Gene silencing, enzyme expression and warfarin sensitivity evidence_span: {"source_cache": "artifacts/k2-research/14765195.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "32f373fc0363ed079e580b2d47a3cb36c82b46871860fc6740b0285e23936496", "start_char": 0, "end_char": 1385, "text_sha256": "32f373fc0363ed079e580b2d47a3cb36c82b46871860fc6740b0285e23936496"} [k2-p14765195] Identification of the gene for vitamin K epoxide reductase. (2004). https://pubmed.ncbi.nlm.nih.gov/14765195/ DOI: 10.1038/nature02254
Complete structured claim and evidence

Availability and dependencies

Each situation shows the normal role first, then what the sources report under a specific condition. A shortfall in the diet, a fault in the machinery, and a low blood reading are kept separate because they are not the same thing.

An impaired enzyme partner interaction slows coumarin metabolism

Condition: machinery_impairment · Experimental CYP2A6 K476E substitution

Normal role: CYP2A6 receives reducing equivalents through its reductase partner.

Recorded consequence: Reduced reductase affinity, electron-transfer measures and coumarin hydroxylation

Scope: Reconstituted human enzyme; no clinical deficiency threshold

Inherited CYP2A6 variation changes coumarin processing

Condition: machinery_impairment · Study-defined CYP2A6 variant alleles

Normal role: CYP2A6 supports coumarin 7-hydroxylation.

Recorded consequence: Reduced ability to metabolize the coumarin probe

Scope: Human genotype/phenotype study; not a coumarin shortage

The sources

Every document behind this chapter is preserved word for word. Open one to read it in full with its recorded conflicts marked in place.

Ceylon cinnamon: metabolism, signaling and nutrient connections (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Coumarin: metabolism, signaling and nutrient connections (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Glutathione: metabolism, signaling and nutrient connections (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Mangiferin: metabolism, signaling and nutrient connections (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source

Recorded disagreements

Where two sources say different things, both are kept and the difference is explained. You can discuss a disagreement or propose a mechanism that might account for it.

Coumarin lymphedema benefit was not reproduced in a larger trialThe 1993 crossover trial reported reduced postmastectomy arm edema; the 1999 replication in 140 women found no benefit despite the same total daily coumarin dose and six-month periods. This is an efficacy disagreement between primary studies, not an author correction.Read the recorded disagreement

Open questions in this collection

Questions the curators could not answer from the sources in front of them, kept here with the reason each one is still open. These are gaps in this collection, not findings or proof that no one has studied them.

Which exact human aldehyde-oxidizing and conjugating isoforms control coumarin disposal in each tissue?The selected detoxification experiments resolve cytosolic activity but not every responsible gene; no specific ALDH isoform is invented.
Why did the two randomized lymphedema trials disagree?No demonstrated mechanism in the selected studies resolves the discrepancy; discussion should test explanations against actual trial details.
Do food-level coumarin exposures cause clinically meaningful interactions with CYP2A6 substrates or inhibitors?Shared metabolism and in vitro inhibition generate testable hypotheses; they do not establish dose changes or clinical outcomes.
Does low glutathione availability increase coumarin injury in people, and would repletion prevent it?The conjugation branch is demonstrated, but this collection contains no human nutrient-depletion or rescue trial.
Can CYP2A6 genotype reliably predict coumarin-associated liver injury?Poor probe metabolism is not itself a validated hepatotoxicity prediction rule.
Which molecular targets explain edema responses, and do those mechanisms operate at achievable human exposures?Animal proteolysis proposals and macrophage morphology do not resolve the contradictory human efficacy findings.
Can any parent-coumarin cancer-cell mechanism translate to a clinically useful effect?Culture effects, sometimes at millimolar concentrations, do not establish human treatment or prevention benefit.

Chapters are assembled from supplied drafts and curated literature summaries. Statements remain unverified against the primary studies, and the ledger is not medical advice.

Evidence, AI assistance and curation standards

Coumarin

The mechanisms

The study explicitly distinguished parent 1,2-benzopyrone from anticoagulant coumarin derivatives.

Human CYP2A6 catalyzed conversion of coumarin to 7-hydroxycoumarin.

Coumarin 3,4-epoxide can rearrange spontaneously to the reactive aldehyde o-HPA.

Rat and mouse cytosols conjugated the epoxide with glutathione through enzymatic and nonenzymatic routes.

Pooled human liver cytosols oxidized o-HPA to o-HPAA, with intrinsic clearance over 50-fold greater than rat cytosols.

CYP2A6 variant alleles were identified in individuals with poor coumarin metabolism, including a single-amino-acid inactivating variant.

The 1993 trial reported arm edema declining from 46% to 26% above normal during active treatment (P<0.001).

At six months arm volume changed by +58 mL on coumarin versus +21 mL on placebo (P=0.80).

Serologic liver toxicity occurred in 6% of women during the coumarin trial.

Cytochrome b5 increased CYP2A6-mediated coumarin hydroxylation; kinetic experiments supported electron transfer to the oxygenated enzyme.

CYP2A6 Asn297 hydrogen bonding oriented coumarin within a compact hydrophobic active site for position-selective oxidation.

Methoxsalen filled the CYP2A6 active-site cavity without substantially changing the protein structure.

Mean 7-hydroxycoumarin formation was 1230 of 1420 pmol/min/mg total polar products in the 12-sample human microsomal panel.

Coumarin-derived material bound covalently to human microsomal proteins, averaging 4.8 pmol/min/mg.

Recombinant human CYP1A enzymes catalyzed coumarin epoxidation; CYP1A1 was among the tested human forms.

Recombinant human CYP1A2 catalyzed coumarin 3,4-epoxide formation.

Recombinant human CYP2E1 catalyzed coumarin 3,4-epoxide formation.

Inhibitor experiments attributed up to 67% of whole-mouse-lung microsomal epoxidation to CYP2F2.

CYP3A and CYP1A forms supported minor 3-hydroxylation, experimentally distinct from the epoxide pathway.

The coumarin epoxide glutathione conjugate was isolated and structurally characterized, with glutathione attached at position 3.

Coumarin accelerated tissue protein removal relative to nonmetabolizable PVP in rat edema models; enhanced proteolysis was proposed.

Coumarin increased macrophage morphologies interpreted as recruitment and elicited activity in canine lymphedema.

Coumarin induced G0/G1 arrest in HeLa cells.

Coumarin dose-dependently reduced HeLa mitochondrial membrane potential.

Coumarin reduced BCL2 expression in HeLa cells.

Coumarin reduced Bcl-xL expression in HeLa cells.

Coumarin increased BAX expression in HeLa cells.

Coumarin promoted cytochrome c release from HeLa mitochondria.

Coumarin activated caspase-3 in HeLa cells before apoptosis.

Coumarin inhibited proliferation reversibly after drug removal in the tested malignant cell panel.

7-Hydroxycoumarin also produced dose- and time-dependent reversible growth inhibition.

Coumarin stimulated apoptosis in HL-60, but not the other cell lines tested in this study.

Coumarin inhibited proliferation with IC50 values of 1.59–3.57 mM across this four-cell-line panel.

The 7-hydroxycoumarin glucuronide was ineffective in the proliferation assays where parent and unconjugated metabolite were active.

With cofactors supplied, human cytosolic products were approximately 90% o-HPAA and 10% glutathione conjugate.

All three species reduced o-HPA to o-HPE; this was a major reaction only in rat preparations.

Bovine liver UGT preparation converted 7-hydroxycoumarin and UDP-glucuronic acid into its glucuronide.

Methoxsalen produced mechanism-based CYP2A6 inhibition, with reported inactivation rate 0.5/min.

Tranylcypromine competitively inhibited coumarin 7-hydroxylation, with Ki 0.04 micromolar.

Nicotine inhibited CYP2A6 coumarin hydroxylation within the study inhibitor category of Ki below 200 micromolar.

Warfarin showed little or no CYP2A6 inhibition in this assay, with Ki above 200 micromolar.

CYP2A6 K476E had lower affinity for NADPH-P450 reductase, contributing to reduced catalytic activity.

K476E reduced NADPH oxidation and ferric-enzyme reduction; excess reductase did not restore wild-type coumarin hydroxylation.

Approximately 1% of orally administered coumarin reached systemic circulation unchanged in this pilot study.

7-Hydroxycoumarin glucuronide was measured after oral coumarin, supporting extensive absorption and first-pass metabolism.

Isolated coumarin capsules produced 62.8% mean urinary 7-hydroxycoumarin recovery over eight hours.

Cinnamon-powder capsules produced 56.0% mean urinary metabolite recovery.

Cinnamon tea produced 66.1% mean urinary recovery and the highest early plasma metabolite peaks.

Cinnamon rice pudding produced 54.7% mean urinary metabolite recovery.

Leg edema declined from 25% to 17% above normal in the 1993 trial (P<0.001).

Moderate/large reported benefit occurred in 15% on coumarin versus 10% on placebo (P=0.19).

Crystallography and extracted-flavin analysis identified FAD bound to recombinant human POR.

Crystallography and extracted-flavin analysis identified FMN bound to recombinant human POR.

Human RFK phosphorylates riboflavin to FMN using ATP, yielding ADP; this precedes FLAD1-mediated FAD synthesis.

Human G6PD uses glucose-6-phosphate and catalytic NADP+ to generate NADPH.

Authenticated C. verum bark contained only trace coumarin, whereas the tested cassia-type species contained substantial amounts.

Cinnamaldehyde inhibited recombinant human CYP2A6, with reported IC50 6.1 micromolar; inhibition increased with time and required NADPH.

Mass spectra indicated cinnamaldehyde-associated CYP2A6 apoprotein adduction, with reported mass addition about 132.67 Da; added glutathione did not prevent this measured adduction.

Added glutathione modestly but significantly reduced the extent of cinnamaldehyde-dependent CYP2A6 inhibition.

Cinnamaldehyde-dependent time-dependent inhibition of CYP2A6 required NADPH in the reconstituted assay.

Mangiferin reduced measured CYP2A6 activity in the hepatocyte experiment.

Glutamate-cysteine ligase joins glutamate and cysteine to form gamma-glutamylcysteine in the first glutathione-synthesis step.

Human GSS joins gamma-glutamylcysteine and glycine in an ATP-dependent reaction to form glutathione.

Human GSS crystallized with two magnesium ions, ADP, glutathione and sulfate.

Recombinantly expressed VKORC1 activity was sensitive to warfarin.

Silencing the identified VKORC1 gene reduced vitamin K epoxide reductase activity; recombinant expression restored warfarin-sensitive enzyme activity.

Availability and dependencies

The sources

Recorded disagreements

Open questions in this collection