Reactive oxygen species

evidence_span

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experimental_model

Narrative review of reactive species in hyperbaric oxygen mechanisms

exposure

Clinical hyperbaric oxygen protocols

limitations

A second narrative review by the same group. Recorded for its framing claim only; it is not primary evidence for any individual mechanism.

nutrient_topic

Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

organism

Human and animal

plain_language

The same reactive molecules that can damage tissue are the ones carrying the healing signal.

primary_references

[hbot-p18845776] Oxidative stress is fundamental to hyperbaric oxygen therapy. (2009). https://pubmed.ncbi.nlm.nih.gov/18845776/ DOI: 10.1152/japplphysiol.91004.2008

tissue_or_cell_type

Multiple tissues

Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 88–99

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Narrative review of reactive species in hyperbaric oxygen mechanisms · source_derived_draft · unverified_draft

### hbot-review-oxidative-stress-central The review argues that reactive species of oxygen and nitrogen play a major role in the cell signal transduction cascades through which hyperbaric oxygen mediates wound healing and ameliorates post-ischaemic and inflammatory injuries. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The same reactive molecules that can damage tissue are the ones carrying the healing signal. organism: Human and animal tissue_or_cell_type: Multiple tissues experimental_model: Narrative review of reactive species in hyperbaric oxygen mechanisms limitations: A second narrative review by the same group. Recorded for its framing claim only; it is not primary evidence for any individual mechanism. exposure: Clinical hyperbaric oxygen protocols evidence_span: {"source_cache": "artifacts/hbot-research/18845776.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "eb24faa214730ea0aa0cdd25baa8a6ae6481e6b98bd174f0131c0d117b5d828c", "start_char": 0, "end_char": 600, "text_sha256": "eb24faa214730ea0aa0cdd25baa8a6ae6481e6b98bd174f0131c0d117b5d828c"} [hbot-p18845776] Oxidative stress is fundamental to hyperbaric oxygen therapy. (2009). https://pubmed.ncbi.nlm.nih.gov/18845776/ DOI: 10.1152/japplphysiol.91004.2008

duration

Not stated here

evidence_access

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

experimental_model

Human gingival fibroblasts (HGF-1)

exposure

Nattokinase pretreatment

limitations

The reported pathway has reciprocal regulation between ROS, PI3K/Akt and MAPK, so a single arrow into ROS understates a loop the authors describe as bidirectional.

organism

Human gingival fibroblasts (HGF-1)

plain_language

Nattokinase suppressed NADPH-oxidase-derived reactive-oxygen-species generation in particulate-exposed gingival fibroblasts.

primary_references

Nuclear factor erythroid 2-related factor 2/heme oxygenase-1 activation by nattokinase reduces pro-inflammatory and matrix-degrading mediators in human gingival fibroblasts. (2026) https://pubmed.ncbi.nlm.nih.gov/41585176/ DOI: 10.1016/j.jds.2025.10.022

route

In vitro

tissue

Cell culture, particulate-matter exposure

Nattokinase: what the purified enzyme cleaves, what survives being eaten, and the gap between the two (2026-09-23) · lines 576–576

Original AI-assisted curation built from a supplied entity-first document of 105 entities and 129 claims. Every reference in that document was resolved against live PubMed with its abstract read and its DOI cross-checked on 2026-09-23, and the EFSA novel-food opinion was retrieved and read in full. That check corrected two PMIDs that pointed at unrelated papers, two DOIs, and two papers recorded as carrying no erratum that do carry one; it also reversed three findings the supplied document had stated backwards. Two papers carry a published correction, recorded as such and not as a retraction. Three sources are not indexed in PubMed and are cited by what they have. Laboratory lineages are recorded, so the four papers from one group, the three from another and the two readings of a single applicant dossier cannot be counted as separate lines of support. Study-specific doses, units, populations and limitations retained; activity units are never converted between systems. Not publisher full text. · supports · Human gingival fibroblasts (HGF-1) · source_derived_draft · unverified_draft

Nattokinase suppressed NADPH-oxidase-derived reactive-oxygen-species generation in particulate-exposed gingival fibroblasts.

evidence_span

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experimental_model

Narrative review of therapeutic mechanisms and clinical trial evidence

exposure

Hyperbaric oxygen as used clinically, typically 2.0 to 2.5 atmospheres absolute

limitations

A narrative review, not a primary experiment. It is recorded as the framing source the reader was given; every mechanism it names is also recorded here from its own primary paper.

nutrient_topic

Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

organism

Human, with supporting animal work

plain_language

The therapy works by making the cell produce reactive molecules that carry signals, not simply by supplying more oxygen.

primary_references

[hbot-p21200283] Hyperbaric oxygen: its mechanisms and efficacy. (2011). https://pubmed.ncbi.nlm.nih.gov/21200283/ DOI: 10.1097/prs.0b013e3181fbe2bf

tissue_or_cell_type

Multiple tissues

Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 62–73

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Narrative review of therapeutic mechanisms and clinical trial evidence · source_derived_draft · unverified_draft

### hbot-review-reactive-species-framing The review states that the principal mechanisms of hyperbaric oxygen are based on intracellular generation of reactive species of oxygen and nitrogen, which act through cell signal transduction cascades. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The therapy works by making the cell produce reactive molecules that carry signals, not simply by supplying more oxygen. organism: Human, with supporting animal work tissue_or_cell_type: Multiple tissues experimental_model: Narrative review of therapeutic mechanisms and clinical trial evidence limitations: A narrative review, not a primary experiment. It is recorded as the framing source the reader was given; every mechanism it names is also recorded here from its own primary paper. exposure: Hyperbaric oxygen as used clinically, typically 2.0 to 2.5 atmospheres absolute evidence_span: {"source_cache": "artifacts/hbot-research/21200283.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "541f2eb700a843e35093e589069b7839f1a3577c2de8cd1edb444698c1379380", "start_char": 0, "end_char": 1120, "text_sha256": "541f2eb700a843e35093e589069b7839f1a3577c2de8cd1edb444698c1379380"} [hbot-p21200283] Hyperbaric oxygen: its mechanisms and efficacy. (2011). https://pubmed.ncbi.nlm.nih.gov/21200283/ DOI: 10.1097/prs.0b013e3181fbe2bf

duration

Not stated here

evidence_access

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

experimental_model

Acute myeloid leukemia cell lines and primary patient samples, with three mouse leukemia models

exposure

Low micromolar ivermectin; mouse dosing described as appearing pharmacologically achievable

limitations

Death was preferential for leukemia cells over normal hematopoietic cells rather than exclusive to them, and synergy was reported with cytarabine and daunorubicin, which also raise reactive oxygen species.

organism

Acute myeloid leukemia cell lines and primary patient samples, with three mouse leukemia models

plain_language

Ivermectin increased reactive oxygen species generation in leukemia cells, and that increase was functionally required for ivermectin-induced cell death.

primary_references

The antiparasitic agent ivermectin induces chloride-dependent membrane hyperpolarization and cell death in leukemia cells. (2010). https://pubmed.ncbi.nlm.nih.gov/20644115/ DOI: 10.1182/blood-2010-01-262675

route

In vitro and in vivo

tissue

Reactive oxygen species and cell viability

Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 189–198

Original AI-assisted curation of sixteen primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Study-specific citations, concentrations, negative findings and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

## ivermectin-leukemia-reactive-oxygen Ivermectin increased reactive oxygen species generation in leukemia cells, and that increase was functionally required for ivermectin-induced cell death. Model/species: Acute myeloid leukemia cell lines and primary patient samples, with three mouse leukemia models Tissue/system: Reactive oxygen species and cell viability Exposure: Low micromolar ivermectin; mouse dosing described as appearing pharmacologically achievable Route: In vitro and in vivo Duration: Not stated here Limits: Death was preferential for leukemia cells over normal hematopoietic cells rather than exclusive to them, and synergy was reported with cytarabine and daunorubicin, which also raise reactive oxygen species. Primary reference: The antiparasitic agent ivermectin induces chloride-dependent membrane hyperpolarization and cell death in leukemia cells. (2010). https://pubmed.ncbi.nlm.nih.gov/20644115/ DOI: 10.1182/blood-2010-01-262675 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_span

{"source_cache": "artifacts/glucan-research/12719479.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "297eb222223ff6861d6890a273716f4cfb3f3c14f887c57c057c2af524f8b425", "start_char": 0, "end_char": 1588, "text_sha256": "297eb222223ff6861d6890a273716f4cfb3f3c14f887c57c057c2af524f8b425"}

experimental_model

Dectin-1 and Toll-like receptor co-expression with phagosome recruitment and cytokine measurement

exposure

Beta-glucan-containing zymosan particles on cells expressing dectin-1 with and without Toll-like receptor signalling

limitations

The particle is zymosan, which carries mannan and other yeast wall components as well as glucan, so a response to zymosan is not by itself a response to purified beta-glucan.

nutrient_topic

Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. · Beta-glucan

organism

Mouse

plain_language

The glucan receptor does not work alone; paired with a bacterial sensor the same particle produces far more than either would.

primary_references

[bg-p12719479] Collaborative induction of inflammatory responses by dectin-1 and Toll-like receptor 2. (2003). https://pubmed.ncbi.nlm.nih.gov/12719479/ DOI: 10.1084/jem.20021787

tissue_or_cell_type

Macrophage and dendritic cell

Beta-glucan: a structural family rather than an agent, what decides whether a bound glucan actually signals, the complement route that a cereal and a yeast preparation share, and the unequal human evidence behind each (2026-09-22) · lines 190–201

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dectin-1 and Toll-like receptor co-expression with phagosome recruitment and cytokine measurement · source_derived_draft · unverified_draft

### bg-dectin1-works-with-tlr2 Dectin-1 is recruited to phagosomes containing zymosan particles but not to phagosomes containing immunoglobulin G-opsonised particles, dectin-1 expression enhances Toll-like receptor-mediated activation of nuclear factor kappa B by beta-glucan-containing particles, and in macrophages and dendritic cells dectin-1 and Toll-like receptors are synergistic in mediating production of cytokines such as interleukin 12 and tumour necrosis factor alpha, while dectin-1 triggers production of reactive oxygen species, an inflammatory response that is primed by Toll-like receptor activation. Condition category: normal nutrient_topic: Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. plain_language: The glucan receptor does not work alone; paired with a bacterial sensor the same particle produces far more than either would. organism: Mouse tissue_or_cell_type: Macrophage and dendritic cell experimental_model: Dectin-1 and Toll-like receptor co-expression with phagosome recruitment and cytokine measurement limitations: The particle is zymosan, which carries mannan and other yeast wall components as well as glucan, so a response to zymosan is not by itself a response to purified beta-glucan. exposure: Beta-glucan-containing zymosan particles on cells expressing dectin-1 with and without Toll-like receptor signalling evidence_span: {"source_cache": "artifacts/glucan-research/12719479.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "297eb222223ff6861d6890a273716f4cfb3f3c14f887c57c057c2af524f8b425", "start_char": 0, "end_char": 1588, "text_sha256": "297eb222223ff6861d6890a273716f4cfb3f3c14f887c57c057c2af524f8b425"} [bg-p12719479] Collaborative induction of inflammatory responses by dectin-1 and Toll-like receptor 2. (2003). https://pubmed.ncbi.nlm.nih.gov/12719479/ DOI: 10.1084/jem.20021787

evidence_span

{"source_cache": "artifacts/glucan-research/21525931.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5bb7dfc847efb60e644eeaf672d3277d18bca9c4fc75051c8d568d8e5dc450e0", "start_char": 0, "end_char": 1406, "text_sha256": "5bb7dfc847efb60e644eeaf672d3277d18bca9c4fc75051c8d568d8e5dc450e0"}

experimental_model

Comparison of soluble and particulate beta-glucan polymers on Dectin-1 signalling, with imaging of receptor and phosphatase distribution

exposure

Soluble against particulate beta-glucan polymers on Dectin-1-expressing phagocytes

limitations

The abstract reports the soluble-versus-particulate comparison and the phosphatase exclusion. It does not state what happens when a soluble glucan is immobilised, so no claim here rests on that.

nutrient_topic

Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. · Beta-glucan

organism

Mouse

plain_language

Binding was not enough: the receptor only fired when particles packed it into a patch that shut out the enzymes which switch it off.

primary_references

[bg-p21525931] Activation of the innate immune receptor Dectin-1 upon formation of a 'phagocytic synapse'. (2011). https://pubmed.ncbi.nlm.nih.gov/21525931/ DOI: 10.1038/nature10071

tissue_or_cell_type

Myeloid phagocytes

Beta-glucan: a structural family rather than an agent, what decides whether a bound glucan actually signals, the complement route that a cereal and a yeast preparation share, and the unequal human evidence behind each (2026-09-22) · lines 138–149

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Comparison of soluble and particulate beta-glucan polymers on Dectin-1 signalling, with imaging of receptor and phosphatase distribution · source_derived_draft · unverified_draft

### bg-only-particles-signal Despite its ability to bind both soluble and particulate beta-glucan polymers, Dectin-1 signalling is only activated by particulate beta-glucans, which cluster the receptor in synapse-like structures from which the regulatory tyrosine phosphatases CD45 and CD148 are excluded, providing a model mechanism by which innate immune receptors can distinguish direct microbial contact from detection of microbes at a distance and initiate direct cellular antimicrobial responses only when they are required. Condition category: normal nutrient_topic: Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. plain_language: Binding was not enough: the receptor only fired when particles packed it into a patch that shut out the enzymes which switch it off. organism: Mouse tissue_or_cell_type: Myeloid phagocytes experimental_model: Comparison of soluble and particulate beta-glucan polymers on Dectin-1 signalling, with imaging of receptor and phosphatase distribution limitations: The abstract reports the soluble-versus-particulate comparison and the phosphatase exclusion. It does not state what happens when a soluble glucan is immobilised, so no claim here rests on that. exposure: Soluble against particulate beta-glucan polymers on Dectin-1-expressing phagocytes evidence_span: {"source_cache": "artifacts/glucan-research/21525931.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5bb7dfc847efb60e644eeaf672d3277d18bca9c4fc75051c8d568d8e5dc450e0", "start_char": 0, "end_char": 1406, "text_sha256": "5bb7dfc847efb60e644eeaf672d3277d18bca9c4fc75051c8d568d8e5dc450e0"} [bg-p21525931] Activation of the innate immune receptor Dectin-1 upon formation of a 'phagocytic synapse'. (2011). https://pubmed.ncbi.nlm.nih.gov/21525931/ DOI: 10.1038/nature10071

evidence_span

{"source_cache": "artifacts/glucan-research/15956283.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "05fbe0dae04d44d8af5946504f066c104e7a294b29d35d70463d50874ec7b41c", "start_char": 0, "end_char": 990, "text_sha256": "05fbe0dae04d44d8af5946504f066c104e7a294b29d35d70463d50874ec7b41c"}

experimental_model

Measurement of Syk activation and reactive oxygen production in macrophage subpopulations

exposure

Dectin-1 stimulation with assessment of Syk activation, reactive oxygen production and phagocytosis

limitations

The heterogeneity finding is the important limit: the pathway operated in a subpopulation in equilibrium with cells that could not use it, and the proportion shifted with cytokine treatment.

nutrient_topic

Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. · Beta-glucan

organism

Mouse

plain_language

One kinase carries the oxidative burst but not the swallowing, and only some of the cells can run it at any moment.

primary_references

[bg-p15956283] Dectin-1 activates Syk tyrosine kinase in a dynamic subset of macrophages for reactive oxygen production. (2005). https://pubmed.ncbi.nlm.nih.gov/15956283/ DOI: 10.1182/blood-2005-03-1239

tissue_or_cell_type

Macrophage

Beta-glucan: a structural family rather than an agent, what decides whether a bound glucan actually signals, the complement route that a cereal and a yeast preparation share, and the unequal human evidence behind each (2026-09-22) · lines 398–409

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Measurement of Syk activation and reactive oxygen production in macrophage subpopulations · source_derived_draft · unverified_draft

### bg-syk-carries-the-oxidative-burst Dectin-1 activates Syk in macrophages and is important for Dectin-1-stimulated reactive oxygen production but not for phagocytosis, Syk activation is restricted to a subpopulation of macrophages that is in equilibrium with cells that cannot activate the pathway, and the proportion of macrophages using this signalling pathway can be modulated by cytokine treatment, so Dectin-1 signalling reveals dynamic macrophage heterogeneity in inflammatory activation potential. Condition category: normal nutrient_topic: Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. plain_language: One kinase carries the oxidative burst but not the swallowing, and only some of the cells can run it at any moment. organism: Mouse tissue_or_cell_type: Macrophage experimental_model: Measurement of Syk activation and reactive oxygen production in macrophage subpopulations limitations: The heterogeneity finding is the important limit: the pathway operated in a subpopulation in equilibrium with cells that could not use it, and the proportion shifted with cytokine treatment. exposure: Dectin-1 stimulation with assessment of Syk activation, reactive oxygen production and phagocytosis evidence_span: {"source_cache": "artifacts/glucan-research/15956283.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "05fbe0dae04d44d8af5946504f066c104e7a294b29d35d70463d50874ec7b41c", "start_char": 0, "end_char": 990, "text_sha256": "05fbe0dae04d44d8af5946504f066c104e7a294b29d35d70463d50874ec7b41c"} [bg-p15956283] Dectin-1 activates Syk tyrosine kinase in a dynamic subset of macrophages for reactive oxygen production. (2005). https://pubmed.ncbi.nlm.nih.gov/15956283/ DOI: 10.1182/blood-2005-03-1239

evidence_span

{"source_cache": "artifacts/hbot-research/32791151.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "106ed876131af9161051c4c178d88af4afd707a20e56a91447d35aa9ed290188", "start_char": 0, "end_char": 1662, "text_sha256": "106ed876131af9161051c4c178d88af4afd707a20e56a91447d35aa9ed290188"}

experimental_model

Diabetic foot mouse model with human skin fibroblasts and human umbilical vein endothelial cells

exposure

Hyperbaric oxygen with high glucose in vitro

limitations

Cell and mouse work with expression endpoints. Tube formation is an angiogenesis surrogate, not a vessel in a person.

nutrient_topic

Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

organism

Mouse and human cells

plain_language

Endothelial cells organise into tubes and fibroblasts start moving and dividing.

primary_references

[hbot-p32791151] Hyperbaric oxygen potentiates diabetic wound healing by promoting fibroblast cell proliferation and endothelial cell angiogenesis. (2020). https://pubmed.ncbi.nlm.nih.gov/32791151/ DOI: 10.1016/j.lfs.2020.118246

tissue_or_cell_type

Skin wound, fibroblasts and endothelium

Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 673–684

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Diabetic foot mouse model with human skin fibroblasts and human umbilical vein endothelial cells · source_derived_draft · unverified_draft

### hbot-endothelial-tube Hyperbaric oxygen stimulated proliferation, migration and tube formation in human umbilical vein endothelial cells, and proliferation, migration and reactive oxygen species production in human skin fibroblasts. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Endothelial cells organise into tubes and fibroblasts start moving and dividing. organism: Mouse and human cells tissue_or_cell_type: Skin wound, fibroblasts and endothelium experimental_model: Diabetic foot mouse model with human skin fibroblasts and human umbilical vein endothelial cells limitations: Cell and mouse work with expression endpoints. Tube formation is an angiogenesis surrogate, not a vessel in a person. exposure: Hyperbaric oxygen with high glucose in vitro evidence_span: {"source_cache": "artifacts/hbot-research/32791151.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "106ed876131af9161051c4c178d88af4afd707a20e56a91447d35aa9ed290188", "start_char": 0, "end_char": 1662, "text_sha256": "106ed876131af9161051c4c178d88af4afd707a20e56a91447d35aa9ed290188"} [hbot-p32791151] Hyperbaric oxygen potentiates diabetic wound healing by promoting fibroblast cell proliferation and endothelial cell angiogenesis. (2020). https://pubmed.ncbi.nlm.nih.gov/32791151/ DOI: 10.1016/j.lfs.2020.118246

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/hbot-research/32066777.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f8915aa50d5b22722e66d20eb0542c6bb03b76a3182d37215a53bc9238ac697d", "start_char": 0, "end_char": 1357, "text_sha256": "f8915aa50d5b22722e66d20eb0542c6bb03b76a3182d37215a53bc9238ac697d"}

experimental_model

Contused rat skeletal muscle with a reactive oxygen species scavenger and a nitric oxide synthase inhibitor

exposure

2.5 ATA 100% oxygen for 120 minutes daily for 5 consecutive days

limitations

Both inhibitors were given before treatment, which is what makes the requirement claim interpretable. The exposure is a therapy-like protocol, unlike the extreme-pressure studies recorded elsewhere here.

nutrient_topic

Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

organism

Rat

plain_language

Mopping up the reactive species, or blocking nitric oxide production, cancels the benefit.

primary_references

[hbot-p32066777] VEGF and bFGF induction by nitric oxide is associated with hyperbaric oxygen-induced angiogenesis and muscle regeneration. (2020). https://pubmed.ncbi.nlm.nih.gov/32066777/ DOI: 10.1038/s41598-020-59615-x

tissue_or_cell_type

Skeletal muscle

trigger_kind

machinery_impairment Imported condition classification; unverified.

Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 699–710

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Contused rat skeletal muscle with a reactive oxygen species scavenger and a nitric oxide synthase inhibitor · source_derived_draft · unverified_draft

### hbot-nac-lname-block Administration of either N-acetylcysteine or L-NAME before treatment suppressed angiogenesis and muscle regeneration even after hyperbaric oxygen. Condition category: machinery_impairment nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Mopping up the reactive species, or blocking nitric oxide production, cancels the benefit. organism: Rat tissue_or_cell_type: Skeletal muscle experimental_model: Contused rat skeletal muscle with a reactive oxygen species scavenger and a nitric oxide synthase inhibitor limitations: Both inhibitors were given before treatment, which is what makes the requirement claim interpretable. The exposure is a therapy-like protocol, unlike the extreme-pressure studies recorded elsewhere here. exposure: 2.5 ATA 100% oxygen for 120 minutes daily for 5 consecutive days evidence_span: {"source_cache": "artifacts/hbot-research/32066777.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f8915aa50d5b22722e66d20eb0542c6bb03b76a3182d37215a53bc9238ac697d", "start_char": 0, "end_char": 1357, "text_sha256": "f8915aa50d5b22722e66d20eb0542c6bb03b76a3182d37215a53bc9238ac697d"} [hbot-p32066777] VEGF and bFGF induction by nitric oxide is associated with hyperbaric oxygen-induced angiogenesis and muscle regeneration. (2020). https://pubmed.ncbi.nlm.nih.gov/32066777/ DOI: 10.1038/s41598-020-59615-x

evidence_span

{"source_cache": "artifacts/dihydrocapsaicin-research/30090648.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e688b4cd16fdd3847d8fe10113d243edf17839f32bef46fe85790a18ad6b920c", "start_char": 0, "end_char": 2110, "text_sha256": "e688b4cd16fdd3847d8fe10113d243edf17839f32bef46fe85790a18ad6b920c"}

experimental_model

Randomised seven-group study in 144 male Sprague Dawley rats after middle cerebral artery occlusion

exposure

Low-dose dihydrocapsaicin at 0.5 mg/kg or high-dose at 1.5 mg/kg, an ice pad at 31 degrees, and the combination, with an external-temperature-control arm

limitations

A large randomised design with a dose-response surprise: the high dose alone did nothing while the low dose worked. That non-monotonicity is recorded because it contradicts the simple dose-response in the other records.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Rat

plain_language

Drug plus ice pack cooled faster and protected better than either on its own.

primary_references

[dhc-p30090648] Synergistically Induced Hypothermia and Enhanced Neuroprotection by Pharmacological and Physical Approaches in Stroke. (2018). https://pubmed.ncbi.nlm.nih.gov/30090648/ DOI: 10.14336/ad.2017.0817

tissue_or_cell_type

Brain

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 335–346

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomised seven-group study in 144 male Sprague Dawley rats after middle cerebral artery occlusion · source_derived_draft · unverified_draft

### dhc-combination-beats-either Combination therapy of low-dose dihydrocapsaicin and an ice pad significantly improved every measured outcome compared with monotherapies, achieving hypothermia faster by 28.6% than the ice pad, 350% than low-dose dihydrocapsaicin and 200% than high-dose dihydrocapsaicin alone, reducing neurological deficits by 63% against 26% with low-dose alone, reducing reactive oxygen species at 6 and 24 hours, increasing ATP by 42.9% against 25%, and decreasing apoptotic cell death by 48.5% against 24.9%. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: Drug plus ice pack cooled faster and protected better than either on its own. organism: Rat tissue_or_cell_type: Brain experimental_model: Randomised seven-group study in 144 male Sprague Dawley rats after middle cerebral artery occlusion limitations: A large randomised design with a dose-response surprise: the high dose alone did nothing while the low dose worked. That non-monotonicity is recorded because it contradicts the simple dose-response in the other records. exposure: Low-dose dihydrocapsaicin at 0.5 mg/kg or high-dose at 1.5 mg/kg, an ice pad at 31 degrees, and the combination, with an external-temperature-control arm evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/30090648.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e688b4cd16fdd3847d8fe10113d243edf17839f32bef46fe85790a18ad6b920c", "start_char": 0, "end_char": 2110, "text_sha256": "e688b4cd16fdd3847d8fe10113d243edf17839f32bef46fe85790a18ad6b920c"} [dhc-p30090648] Synergistically Induced Hypothermia and Enhanced Neuroprotection by Pharmacological and Physical Approaches in Stroke. (2018). https://pubmed.ncbi.nlm.nih.gov/30090648/ DOI: 10.14336/ad.2017.0817

evidence_span

{"source_cache": "artifacts/dihydrocapsaicin-research/27748914.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ffc172fb64714099772462ba33304b69637efac75f1f218f2032e26bbc32dc90", "start_char": 0, "end_char": 1610, "text_sha256": "ffc172fb64714099772462ba33304b69637efac75f1f218f2032e26bbc32dc90"}

experimental_model

U251 human glioma cells with flow cytometry, transmission electron microscopy and a murine xenograft model

exposure

Capsaicin and dihydrocapsaicin applied across doses and times, with L929 normal fibroblasts as a selectivity control

limitations

Includes a normal-cell control and an in vivo arm. Cell-line concentrations are not stated in the abstract and are not assumed here.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Human cells and mouse

plain_language

It kills glioma cells through the mitochondria while largely sparing normal cells.

primary_references

[dhc-p27748914] Capsaicin and dihydrocapsaicin induce apoptosis in human glioma cells via ROS and Ca2+‑mediated mitochondrial pathway. (2016). https://pubmed.ncbi.nlm.nih.gov/27748914/ DOI: 10.3892/mmr.2016.5784

tissue_or_cell_type

Glioma cells

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 712–723

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · U251 human glioma cells with flow cytometry, transmission electron microscopy and a murine xenograft model · source_derived_draft · unverified_draft

### dhc-glioma-apoptosis Treatment of U251 glioma cells with capsaicin and dihydrocapsaicin resulted in a dose- and time-dependent inhibition of cell viability and induction of apoptosis, whereas few effects were observed on the viability of L929 normal murine fibroblast cells, and the apoptosis was associated with generation of reactive oxygen species, increased calcium concentrations, mitochondrial depolarization, release of cytochrome c into the cytosol and activation of caspase-9 and caspase-3, with anti-tumour effects confirmed in a murine tumour xenograft model. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: It kills glioma cells through the mitochondria while largely sparing normal cells. organism: Human cells and mouse tissue_or_cell_type: Glioma cells experimental_model: U251 human glioma cells with flow cytometry, transmission electron microscopy and a murine xenograft model limitations: Includes a normal-cell control and an in vivo arm. Cell-line concentrations are not stated in the abstract and are not assumed here. exposure: Capsaicin and dihydrocapsaicin applied across doses and times, with L929 normal fibroblasts as a selectivity control evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/27748914.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ffc172fb64714099772462ba33304b69637efac75f1f218f2032e26bbc32dc90", "start_char": 0, "end_char": 1610, "text_sha256": "ffc172fb64714099772462ba33304b69637efac75f1f218f2032e26bbc32dc90"} [dhc-p27748914] Capsaicin and dihydrocapsaicin induce apoptosis in human glioma cells via ROS and Ca2+‑mediated mitochondrial pathway. (2016). https://pubmed.ncbi.nlm.nih.gov/27748914/ DOI: 10.3892/mmr.2016.5784

evidence_span

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experimental_model

Rat multizone perforator flap ischaemia-reperfusion model with network pharmacology prediction and pathway manipulation

exposure

Dihydrocapsaicin with cGAS-STING pathway activation as a test of mediation

limitations

The pathway-activation arm is the useful control: switching the pathway back on removed the benefit. Network pharmacology prediction is hypothesis generation, not evidence.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Rat

plain_language

It protects starved tissue by switching off an inflammatory alarm; turn the alarm back on and the protection goes.

primary_references

[dhc-p38459660] Dihydrocapsaicin suppresses the STING-mediated accumulation of ROS and NLRP3 inflammasome and alleviates apoptosis after ischemia-reperfusion injury of perforator skin flap. (2024). https://pubmed.ncbi.nlm.nih.gov/38459660/ DOI: 10.1002/ptr.8167

tissue_or_cell_type

Skin flap vasculature

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 699–710

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat multizone perforator flap ischaemia-reperfusion model with network pharmacology prediction and pathway manipulation · source_derived_draft · unverified_draft

### dhc-suppresses-sting Dihydrocapsaicin enhanced the survival of multizone perforator flaps by suppressing the cGAS-STING pathway, oxidative stress and formation of the NLRP3 inflammasome, inducing oxidative stress resistance and preventing apoptosis in vascular endothelial cells, whereas activation of the cGAS-STING pathway led to accumulation of reactive oxygen species and NLRP3 inflammasome and diminished the protective role of dihydrocapsaicin. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: It protects starved tissue by switching off an inflammatory alarm; turn the alarm back on and the protection goes. organism: Rat tissue_or_cell_type: Skin flap vasculature experimental_model: Rat multizone perforator flap ischaemia-reperfusion model with network pharmacology prediction and pathway manipulation limitations: The pathway-activation arm is the useful control: switching the pathway back on removed the benefit. Network pharmacology prediction is hypothesis generation, not evidence. exposure: Dihydrocapsaicin with cGAS-STING pathway activation as a test of mediation evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/38459660.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f1a586e910230094fc4d9c5c54d57fb7ccab56a5c6565737d15a38c16f0567cf", "start_char": 0, "end_char": 1793, "text_sha256": "f1a586e910230094fc4d9c5c54d57fb7ccab56a5c6565737d15a38c16f0567cf"} [dhc-p38459660] Dihydrocapsaicin suppresses the STING-mediated accumulation of ROS and NLRP3 inflammasome and alleviates apoptosis after ischemia-reperfusion injury of perforator skin flap. (2024). https://pubmed.ncbi.nlm.nih.gov/38459660/ DOI: 10.1002/ptr.8167