Nutrient chapter

Ivermectin

Semi-synthetic macrocyclic lactone derived from avermectin B1a. Species, preparation, concentration and limitations are retained on linked claims.

30 recorded mechanisms · 0 availability situations · 7 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.

An avermectin-sensitive glutamate-gated chloride channel was cloned from Caenorhabditis elegans and shown to be a new member of the ligand-gated ion channel superfamily.
Avermectin → Caenorhabditis elegans glutamate-gated chloride channel alpha / GluCl source_derived_draftungraded
Experimental context and source evidence
duration
Acute
evidence_access
Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
experimental_model
Caenorhabditis elegans complementary DNAs expressed in Xenopus oocytes
exposure
Avermectin applied to the expressed channel
limitations
The same report notes that avermectins also interact with vertebrate and invertebrate GABA receptors, so an invertebrate-only target cannot be inferred from this channel alone.
organism
Caenorhabditis elegans complementary DNAs expressed in Xenopus oocytes
plain_language
An avermectin-sensitive glutamate-gated chloride channel was cloned from Caenorhabditis elegans and shown to be a new member of the ligand-gated ion channel superfamily.
primary_references
Cloning of an avermectin-sensitive glutamate-gated chloride channel from Caenorhabditis elegans. (1994). https://pubmed.ncbi.nlm.nih.gov/7935817/ DOI: 10.1038/371707a0
route
In vitro
tissue
Expression cloning and electrophysiology of a glutamate-gated chloride channel
Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 13–22
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-glucl-cloning An avermectin-sensitive glutamate-gated chloride channel was cloned from Caenorhabditis elegans and shown to be a new member of the ligand-gated ion channel superfamily. Model/species: Caenorhabditis elegans complementary DNAs expressed in Xenopus oocytes Tissue/system: Expression cloning and electrophysiology of a glutamate-gated chloride channel Exposure: Avermectin applied to the expressed channel Route: In vitro Duration: Acute Limits: The same report notes that avermectins also interact with vertebrate and invertebrate GABA receptors, so an invertebrate-only target cannot be inferred from this channel alone. Primary reference: Cloning of an avermectin-sensitive glutamate-gated chloride channel from Caenorhabditis elegans. (1994). https://pubmed.ncbi.nlm.nih.gov/7935817/ DOI: 10.1038/371707a0 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
Complete structured claim and evidence
Ivermectin binds in the transmembrane domain of the Caenorhabditis elegans glutamate-gated chloride channel and stabilises an open-pore conformation.
Ivermectin → Caenorhabditis elegans glutamate-gated chloride channel alpha / GluCl source_derived_draftungraded
Experimental context and source evidence
duration
Not applicable
evidence_access
Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
experimental_model
Homopentameric Caenorhabditis elegans GluCl alpha, X-ray structure at 3.3 angstrom resolution
exposure
GluCl-Fab complex determined with ivermectin as allosteric agonist, and separately with L-glutamate and picrotoxin
limitations
A structure establishes a binding site and a stabilised conformation; it does not establish the concentration at which this occurs in a living parasite.
organism
Homopentameric Caenorhabditis elegans GluCl alpha, X-ray structure at 3.3 angstrom resolution
plain_language
Ivermectin binds in the transmembrane domain of the Caenorhabditis elegans glutamate-gated chloride channel and stabilises an open-pore conformation.
primary_references
Principles of activation and permeation in an anion-selective Cys-loop receptor. (2011). https://pubmed.ncbi.nlm.nih.gov/21572436/ DOI: 10.1038/nature10139
route
Structural
tissue
Anion-selective Cys-loop receptor gating and permeation
Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 24–33
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-glucl-open-pore Ivermectin binds in the transmembrane domain of the Caenorhabditis elegans glutamate-gated chloride channel and stabilises an open-pore conformation. Model/species: Homopentameric Caenorhabditis elegans GluCl alpha, X-ray structure at 3.3 angstrom resolution Tissue/system: Anion-selective Cys-loop receptor gating and permeation Exposure: GluCl-Fab complex determined with ivermectin as allosteric agonist, and separately with L-glutamate and picrotoxin Route: Structural Duration: Not applicable Limits: A structure establishes a binding site and a stabilised conformation; it does not establish the concentration at which this occurs in a living parasite. Primary reference: Principles of activation and permeation in an anion-selective Cys-loop receptor. (2011). https://pubmed.ncbi.nlm.nih.gov/21572436/ DOI: 10.1038/nature10139 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
Complete structured claim and evidence
Ivermectin exposure decreased the amount of protein released from the excretory-secretory apparatus of Brugia malayi microfilariae.
Ivermectin → Protein release from the Brugia malayi excretory-secretory apparatus source_derived_draftungraded
Experimental context and source evidence
duration
Acute
evidence_access
Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
experimental_model
Brugia malayi microfilariae
exposure
Ivermectin in vitro
limitations
The link from reduced secretion to rapid microfilarial clearance in the host is proposed by the authors, not measured in this work.
organism
Brugia malayi microfilariae
plain_language
Ivermectin exposure decreased the amount of protein released from the excretory-secretory apparatus of Brugia malayi microfilariae.
primary_references
Ivermectin disrupts the function of the excretory-secretory apparatus in microfilariae of Brugia malayi. (2010). https://pubmed.ncbi.nlm.nih.gov/21041637/ DOI: 10.1073/pnas.1011983107
route
In vitro
tissue
Excretory-secretory vesicle and the muscle structure surrounding it, where GluCl expression was localised
Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 35–44
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-es-protein-release Ivermectin exposure decreased the amount of protein released from the excretory-secretory apparatus of Brugia malayi microfilariae. Model/species: Brugia malayi microfilariae Tissue/system: Excretory-secretory vesicle and the muscle structure surrounding it, where GluCl expression was localised Exposure: Ivermectin in vitro Route: In vitro Duration: Acute Limits: The link from reduced secretion to rapid microfilarial clearance in the host is proposed by the authors, not measured in this work. Primary reference: Ivermectin disrupts the function of the excretory-secretory apparatus in microfilariae of Brugia malayi. (2010). https://pubmed.ncbi.nlm.nih.gov/21041637/ DOI: 10.1073/pnas.1011983107 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
Complete structured claim and evidence
Ivermectin had little direct effect on Brugia malayi microfilariae in culture at pharmacologically relevant concentrations.
Ivermectin → Brugia malayi microfilarial viability in culture source_derived_draftungraded
Experimental context and source evidence
duration
Not stated here
evidence_access
Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
experimental_model
Brugia malayi microfilariae in culture
exposure
Pharmacologically relevant ivermectin concentrations
limitations
A null result in culture does not exclude killing in the host, where immune clearance is available; it is the reason the secretion mechanism was investigated.
organism
Brugia malayi microfilariae in culture
plain_language
Ivermectin had little direct effect on Brugia malayi microfilariae in culture at pharmacologically relevant concentrations.
primary_references
Ivermectin disrupts the function of the excretory-secretory apparatus in microfilariae of Brugia malayi. (2010). https://pubmed.ncbi.nlm.nih.gov/21041637/ DOI: 10.1073/pnas.1011983107
route
In vitro
tissue
Parasite viability
Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 46–55
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-microfilaria-direct-kill-null Ivermectin had little direct effect on Brugia malayi microfilariae in culture at pharmacologically relevant concentrations. Model/species: Brugia malayi microfilariae in culture Tissue/system: Parasite viability Exposure: Pharmacologically relevant ivermectin concentrations Route: In vitro Duration: Not stated here Limits: A null result in culture does not exclude killing in the host, where immune clearance is available; it is the reason the secretion mechanism was investigated. Primary reference: Ivermectin disrupts the function of the excretory-secretory apparatus in microfilariae of Brugia malayi. (2010). https://pubmed.ncbi.nlm.nih.gov/21041637/ DOI: 10.1073/pnas.1011983107 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
Complete structured claim and evidence
Mice lacking the mdr1a P-glycoprotein gene showed about one hundred fold increased sensitivity to ivermectin, and mdr1a P-glycoprotein was the major P-glycoprotein of the blood-brain barrier.
Human P-glycoprotein / ABCB1 / MDR1 → Ivermectin concentration in brain source_derived_draftungraded
Experimental context and source evidence
duration
Not stated here
evidence_access
Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
experimental_model
mdr1a homozygous knockout mice compared with wild type
exposure
Ivermectin, described in this report as a centrally neurotoxic pesticide
limitations
The comparison is a complete gene disruption, which is a stronger manipulation than partial pharmacological inhibition of P-glycoprotein.
organism
mdr1a homozygous knockout mice compared with wild type
plain_language
Mice lacking the mdr1a P-glycoprotein gene showed about one hundred fold increased sensitivity to ivermectin, and mdr1a P-glycoprotein was the major P-glycoprotein of the blood-brain barrier.
primary_references
Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. (1994). https://pubmed.ncbi.nlm.nih.gov/7910522/ DOI: 10.1016/0092-8674(94)90212-7
route
In vivo
tissue
Blood-brain barrier and tissue drug distribution
Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 57–66
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
## pgp-restricts-ivermectin-brain-entry Mice lacking the mdr1a P-glycoprotein gene showed about one hundred fold increased sensitivity to ivermectin, and mdr1a P-glycoprotein was the major P-glycoprotein of the blood-brain barrier. Model/species: mdr1a homozygous knockout mice compared with wild type Tissue/system: Blood-brain barrier and tissue drug distribution Exposure: Ivermectin, described in this report as a centrally neurotoxic pesticide Route: In vivo Duration: Not stated here Limits: The comparison is a complete gene disruption, which is a stronger manipulation than partial pharmacological inhibition of P-glycoprotein. Primary reference: Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. (1994). https://pubmed.ncbi.nlm.nih.gov/7910522/ DOI: 10.1016/0092-8674(94)90212-7 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
Complete structured claim and evidence
Ivermectin accumulated thirty-six to sixty fold in the brain of mdr1a,b knockout mice compared with wild type, while selamectin accumulated only five to ten fold.
Mouse mdr1a P-glycoprotein deficiency → Ivermectin concentration in brain source_derived_draftungraded
Experimental context and source evidence
duration
Not stated here
evidence_access
Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
experimental_model
mdr1a,b double knockout mice and bcrp knockout mice, against wild type
exposure
Ivermectin 0.2 mg/kg and selamectin 12 mg/kg, intravenous, oral and dermal spot-on
limitations
Breast cancer resistance protein knockouts showed no difference, so this margin is specific to P-glycoprotein and not to efflux transport in general.
organism
mdr1a,b double knockout mice and bcrp knockout mice, against wild type
plain_language
Ivermectin accumulated thirty-six to sixty fold in the brain of mdr1a,b knockout mice compared with wild type, while selamectin accumulated only five to ten fold.
primary_references
Brain penetration of ivermectin and selamectin in mdr1a,b P-glycoprotein- and bcrp- deficient knockout mice. (2009). https://pubmed.ncbi.nlm.nih.gov/19161460/ DOI: 10.1111/j.1365-2885.2008.01007.x
route
In vivo
tissue
Brain penetration, organ distribution and plasma kinetics
Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 68–77
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-brain-accumulation-without-pgp Ivermectin accumulated thirty-six to sixty fold in the brain of mdr1a,b knockout mice compared with wild type, while selamectin accumulated only five to ten fold. Model/species: mdr1a,b double knockout mice and bcrp knockout mice, against wild type Tissue/system: Brain penetration, organ distribution and plasma kinetics Exposure: Ivermectin 0.2 mg/kg and selamectin 12 mg/kg, intravenous, oral and dermal spot-on Route: In vivo Duration: Not stated here Limits: Breast cancer resistance protein knockouts showed no difference, so this margin is specific to P-glycoprotein and not to efflux transport in general. Primary reference: Brain penetration of ivermectin and selamectin in mdr1a,b P-glycoprotein- and bcrp- deficient knockout mice. (2009). https://pubmed.ncbi.nlm.nih.gov/19161460/ DOI: 10.1111/j.1365-2885.2008.01007.x Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
Complete structured claim and evidence
Preapplication of ivermectin in the micromolar range strongly enhanced the acetylcholine-evoked current of alpha7 nicotinic acetylcholine receptors, acting as a positive allosteric effector.
Ivermectin → Human alpha7 nicotinic acetylcholine receptor / CHRNA7 source_derived_draftungraded
Experimental context and source evidence
duration
Acute
evidence_access
Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
experimental_model
Chick and human alpha7 nicotinic acetylcholine receptors in Xenopus laevis oocytes and K-28 cells
exposure
Micromolar ivermectin preapplication
limitations
Micromolar exposure in a heterologous expression system is well above ordinary antiparasitic plasma concentrations, and the authors exclude a nonspecific chloride current rather than establishing an in vivo effect.
organism
Chick and human alpha7 nicotinic acetylcholine receptors in Xenopus laevis oocytes and K-28 cells
plain_language
Preapplication of ivermectin in the micromolar range strongly enhanced the acetylcholine-evoked current of alpha7 nicotinic acetylcholine receptors, acting as a positive allosteric effector.
primary_references
Ivermectin: a positive allosteric effector of the alpha7 neuronal nicotinic acetylcholine receptor. (1998). https://pubmed.ncbi.nlm.nih.gov/9463487/ DOI: 10.1124/mol.53.2.283
route
In vitro
tissue
Ligand-gated cation channel current
Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 79–88
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-alpha7-nicotinic-potentiation Preapplication of ivermectin in the micromolar range strongly enhanced the acetylcholine-evoked current of alpha7 nicotinic acetylcholine receptors, acting as a positive allosteric effector. Model/species: Chick and human alpha7 nicotinic acetylcholine receptors in Xenopus laevis oocytes and K-28 cells Tissue/system: Ligand-gated cation channel current Exposure: Micromolar ivermectin preapplication Route: In vitro Duration: Acute Limits: Micromolar exposure in a heterologous expression system is well above ordinary antiparasitic plasma concentrations, and the authors exclude a nonspecific chloride current rather than establishing an in vivo effect. Primary reference: Ivermectin: a positive allosteric effector of the alpha7 neuronal nicotinic acetylcholine receptor. (1998). https://pubmed.ncbi.nlm.nih.gov/9463487/ DOI: 10.1124/mol.53.2.283 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
Complete structured claim and evidence
Ivermectin was a specific positive allosteric effector of heterologously expressed P2X4 channels with an EC50 near 250 nanomolar, increasing current amplitude and slowing deactivation.
Ivermectin → P2X4 receptor channel / P2RX4 source_derived_draftungraded
Experimental context and source evidence
duration
Acute
evidence_access
Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
experimental_model
Heterologously expressed P2X4 and P2X4/P2X6 channels
exposure
Submicromolar ivermectin, rapid and reversible
limitations
The effect was specific to P2X4 and absent at P2X2, P2X3, P2X2/P2X3 and P2X7, so it cannot be generalised to ATP signalling as a whole.
organism
Heterologously expressed P2X4 and P2X4/P2X6 channels
plain_language
Ivermectin was a specific positive allosteric effector of heterologously expressed P2X4 channels with an EC50 near 250 nanomolar, increasing current amplitude and slowing deactivation.
primary_references
Allosteric control of gating and kinetics at P2X(4) receptor channels. (1999). https://pubmed.ncbi.nlm.nih.gov/10460235/ DOI: 10.1523/JNEUROSCI.19-17-07289.1999
route
In vitro
tissue
ATP-gated cation channel gating and kinetics
Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 90–99
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-p2x4-potentiation Ivermectin was a specific positive allosteric effector of heterologously expressed P2X4 channels with an EC50 near 250 nanomolar, increasing current amplitude and slowing deactivation. Model/species: Heterologously expressed P2X4 and P2X4/P2X6 channels Tissue/system: ATP-gated cation channel gating and kinetics Exposure: Submicromolar ivermectin, rapid and reversible Route: In vitro Duration: Acute Limits: The effect was specific to P2X4 and absent at P2X2, P2X3, P2X2/P2X3 and P2X7, so it cannot be generalised to ATP signalling as a whole. Primary reference: Allosteric control of gating and kinetics at P2X(4) receptor channels. (1999). https://pubmed.ncbi.nlm.nih.gov/10460235/ DOI: 10.1523/JNEUROSCI.19-17-07289.1999 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
Complete structured claim and evidence
Ivermectin produced no significant effect on fast ATP-evoked inward currents in adult trigeminal mesencephalic nucleus or hippocampal CA1 neurons.
Ivermectin → Native ATP-evoked P2X current in adult neurons source_derived_draftungraded
Experimental context and source evidence
duration
Acute
evidence_access
Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
experimental_model
Adult rat trigeminal mesencephalic nucleus and hippocampal CA1 neurons
exposure
Ivermectin at concentrations that modulated heterologously expressed P2X4
limitations
The authors read this as evidence that homomeric P2X4 is not the primary P2X subtype in these neurons, not as evidence that ivermectin fails to reach the channel.
organism
Adult rat trigeminal mesencephalic nucleus and hippocampal CA1 neurons
plain_language
Ivermectin produced no significant effect on fast ATP-evoked inward currents in adult trigeminal mesencephalic nucleus or hippocampal CA1 neurons.
primary_references
Allosteric control of gating and kinetics at P2X(4) receptor channels. (1999). https://pubmed.ncbi.nlm.nih.gov/10460235/ DOI: 10.1523/JNEUROSCI.19-17-07289.1999
route
In vitro
tissue
Endogenously expressed P2X receptor currents
Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 101–110
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-native-p2x-current-null Ivermectin produced no significant effect on fast ATP-evoked inward currents in adult trigeminal mesencephalic nucleus or hippocampal CA1 neurons. Model/species: Adult rat trigeminal mesencephalic nucleus and hippocampal CA1 neurons Tissue/system: Endogenously expressed P2X receptor currents Exposure: Ivermectin at concentrations that modulated heterologously expressed P2X4 Route: In vitro Duration: Acute Limits: The authors read this as evidence that homomeric P2X4 is not the primary P2X subtype in these neurons, not as evidence that ivermectin fails to reach the channel. Primary reference: Allosteric control of gating and kinetics at P2X(4) receptor channels. (1999). https://pubmed.ncbi.nlm.nih.gov/10460235/ DOI: 10.1523/JNEUROSCI.19-17-07289.1999 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
Complete structured claim and evidence
Ivermectin irreversibly activated human alpha1 homomeric and alpha1beta heteromeric glycine receptors at concentrations at or above 0.03 micromolar, through a site that is not the glycine site.
Ivermectin → Human alpha1 homomeric glycine receptor source_derived_draftungraded
Experimental context and source evidence
duration
Acute and irreversible within the experiment
evidence_access
Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
experimental_model
Recombinant human alpha1 homomeric and alpha1beta heteromeric glycine receptors
exposure
0.03 micromolar potentiation and higher-concentration irreversible activation
limitations
Ivermectin-gated currents showed markedly reduced sensitivity to strychnine, picrotoxin and zinc, so the pharmacology of this activation differs from ordinary glycinergic transmission.
organism
Recombinant human alpha1 homomeric and alpha1beta heteromeric glycine receptors
plain_language
Ivermectin irreversibly activated human alpha1 homomeric and alpha1beta heteromeric glycine receptors at concentrations at or above 0.03 micromolar, through a site that is not the glycine site.
primary_references
Ivermectin, an unconventional agonist of the glycine receptor chloride channel. (2001). https://pubmed.ncbi.nlm.nih.gov/11278873/ DOI: 10.1074/jbc.M011264200
route
In vitro
tissue
Inhibitory chloride channel gating
Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 112–121
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-glycine-receptor-activation Ivermectin irreversibly activated human alpha1 homomeric and alpha1beta heteromeric glycine receptors at concentrations at or above 0.03 micromolar, through a site that is not the glycine site. Model/species: Recombinant human alpha1 homomeric and alpha1beta heteromeric glycine receptors Tissue/system: Inhibitory chloride channel gating Exposure: 0.03 micromolar potentiation and higher-concentration irreversible activation Route: In vitro Duration: Acute and irreversible within the experiment Limits: Ivermectin-gated currents showed markedly reduced sensitivity to strychnine, picrotoxin and zinc, so the pharmacology of this activation differs from ordinary glycinergic transmission. Primary reference: Ivermectin, an unconventional agonist of the glycine receptor chloride channel. (2001). https://pubmed.ncbi.nlm.nih.gov/11278873/ DOI: 10.1074/jbc.M011264200 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
Complete structured claim and evidence
Ivermectin bound the farnesoid X receptor ligand-binding domain and induced its transcriptional activity, with a crystal structure showing a distinct binding mode and an expanded ligand-binding pocket.
Ivermectin → Human farnesoid X receptor / NR1H4 source_derived_draftungraded
Experimental context and source evidence
duration
Not applicable
evidence_access
Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
experimental_model
High-throughput compound library screen, FXR ligand-binding domain crystal structure
exposure
Ivermectin complexed with the FXR ligand-binding domain
limitations
The authors describe FXR as the first mammalian protein targeted by ivermectin with high selectivity, which is a claim about selectivity among mammalian targets rather than about potency.
organism
High-throughput compound library screen, FXR ligand-binding domain crystal structure
plain_language
Ivermectin bound the farnesoid X receptor ligand-binding domain and induced its transcriptional activity, with a crystal structure showing a distinct binding mode and an expanded ligand-binding pocket.
primary_references
The antiparasitic drug ivermectin is a novel FXR ligand that regulates metabolism. (2013). https://pubmed.ncbi.nlm.nih.gov/23728580/ DOI: 10.1038/ncomms2924
route
In vitro and structural
tissue
Nuclear receptor transcriptional activity and coregulator recruitment
Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 123–132
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-fxr-ligand Ivermectin bound the farnesoid X receptor ligand-binding domain and induced its transcriptional activity, with a crystal structure showing a distinct binding mode and an expanded ligand-binding pocket. Model/species: High-throughput compound library screen, FXR ligand-binding domain crystal structure Tissue/system: Nuclear receptor transcriptional activity and coregulator recruitment Exposure: Ivermectin complexed with the FXR ligand-binding domain Route: In vitro and structural Duration: Not applicable Limits: The authors describe FXR as the first mammalian protein targeted by ivermectin with high selectivity, which is a claim about selectivity among mammalian targets rather than about potency. Primary reference: The antiparasitic drug ivermectin is a novel FXR ligand that regulates metabolism. (2013). https://pubmed.ncbi.nlm.nih.gov/23728580/ DOI: 10.1038/ncomms2924 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
Complete structured claim and evidence
Ivermectin decreased serum glucose and cholesterol in wild-type mice but not in FXR-null mice.
Ivermectin → Serum glucose concentration source_derived_draftungraded
Experimental context and source evidence
duration
Not stated here
evidence_access
Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
experimental_model
Wild-type and FXR-null mice
exposure
Ivermectin treatment
limitations
The null-mouse comparison attributes the metabolic effect to FXR; it does not establish a dose relevant to human antiparasitic use.
organism
Wild-type and FXR-null mice
plain_language
Ivermectin decreased serum glucose and cholesterol in wild-type mice but not in FXR-null mice.
primary_references
The antiparasitic drug ivermectin is a novel FXR ligand that regulates metabolism. (2013). https://pubmed.ncbi.nlm.nih.gov/23728580/ DOI: 10.1038/ncomms2924
route
In vivo
tissue
Serum glucose and cholesterol
Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 134–143
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-lowers-glucose-through-fxr Ivermectin decreased serum glucose and cholesterol in wild-type mice but not in FXR-null mice. Model/species: Wild-type and FXR-null mice Tissue/system: Serum glucose and cholesterol Exposure: Ivermectin treatment Route: In vivo Duration: Not stated here Limits: The null-mouse comparison attributes the metabolic effect to FXR; it does not establish a dose relevant to human antiparasitic use. Primary reference: The antiparasitic drug ivermectin is a novel FXR ligand that regulates metabolism. (2013). https://pubmed.ncbi.nlm.nih.gov/23728580/ DOI: 10.1038/ncomms2924 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
Complete structured claim and evidence
Ivermectin inhibited importin alpha/beta-mediated nuclear import broadly, with no effect on a range of other nuclear import pathways including import mediated by importin beta1 alone.
Ivermectin → Importin alpha/beta nuclear import complex source_derived_draftungraded
Experimental context and source evidence
duration
Acute
evidence_access
Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
experimental_model
Nuclear transport assays following a high-throughput screen
exposure
Ivermectin
limitations
Specificity here is specificity among import pathways; the concentration required is not stated in the abstract.
organism
Nuclear transport assays following a high-throughput screen
plain_language
Ivermectin inhibited importin alpha/beta-mediated nuclear import broadly, with no effect on a range of other nuclear import pathways including import mediated by importin beta1 alone.
primary_references
Ivermectin is a specific inhibitor of importin alpha/beta-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus. (2012). https://pubmed.ncbi.nlm.nih.gov/22417684/ DOI: 10.1042/BJ20120150
route
In vitro
tissue
Protein movement between cytoplasm and nucleus
Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 145–154
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-importin-nuclear-import Ivermectin inhibited importin alpha/beta-mediated nuclear import broadly, with no effect on a range of other nuclear import pathways including import mediated by importin beta1 alone. Model/species: Nuclear transport assays following a high-throughput screen Tissue/system: Protein movement between cytoplasm and nucleus Exposure: Ivermectin Route: In vitro Duration: Acute Limits: Specificity here is specificity among import pathways; the concentration required is not stated in the abstract. Primary reference: Ivermectin is a specific inhibitor of importin alpha/beta-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus. (2012). https://pubmed.ncbi.nlm.nih.gov/22417684/ DOI: 10.1042/BJ20120150 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
Complete structured claim and evidence
Ivermectin inhibited replication of HIV-1 and dengue virus, both of which depend on importin alpha/beta nuclear import of HIV-1 integrase and dengue NS5 polymerase respectively.
Ivermectin → HIV-1 and dengue virus replication in culture source_derived_draftungraded
Experimental context and source evidence
duration
Not stated here
evidence_access
Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
experimental_model
HIV-1 and dengue virus replication assays
exposure
Ivermectin
limitations
Antiviral activity in culture is attributed to the import mechanism by inference from the known import dependence of these viral proteins.
organism
HIV-1 and dengue virus replication assays
plain_language
Ivermectin inhibited replication of HIV-1 and dengue virus, both of which depend on importin alpha/beta nuclear import of HIV-1 integrase and dengue NS5 polymerase respectively.
primary_references
Ivermectin is a specific inhibitor of importin alpha/beta-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus. (2012). https://pubmed.ncbi.nlm.nih.gov/22417684/ DOI: 10.1042/BJ20120150
route
In vitro
tissue
Viral protein nuclear import
Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 156–165
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-hiv-dengue-replication Ivermectin inhibited replication of HIV-1 and dengue virus, both of which depend on importin alpha/beta nuclear import of HIV-1 integrase and dengue NS5 polymerase respectively. Model/species: HIV-1 and dengue virus replication assays Tissue/system: Viral protein nuclear import Exposure: Ivermectin Route: In vitro Duration: Not stated here Limits: Antiviral activity in culture is attributed to the import mechanism by inference from the known import dependence of these viral proteins. Primary reference: Ivermectin is a specific inhibitor of importin alpha/beta-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus. (2012). https://pubmed.ncbi.nlm.nih.gov/22417684/ DOI: 10.1042/BJ20120150 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
Complete structured claim and evidence
A single addition of ivermectin to SARS-CoV-2-infected Vero-hSLAM cells two hours after infection produced approximately a five thousand fold reduction in viral RNA at forty-eight hours.
Ivermectin → SARS-CoV-2 viral RNA in Vero-hSLAM culture source_derived_draftungraded
Experimental context and source evidence
duration
48 hours
evidence_access
Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
experimental_model
Vero-hSLAM cell culture
exposure
Single ivermectin addition two hours post infection
limitations
This is a cell-culture result in a monkey kidney line, and the authors state only that it warrants further investigation for possible benefits in humans. The concentration relationship to human plasma exposure is not addressed in the report and remains unresolved here.
organism
Vero-hSLAM cell culture
plain_language
A single addition of ivermectin to SARS-CoV-2-infected Vero-hSLAM cells two hours after infection produced approximately a five thousand fold reduction in viral RNA at forty-eight hours.
primary_references
The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. (2020). https://pubmed.ncbi.nlm.nih.gov/32251768/ DOI: 10.1016/j.antiviral.2020.104787
route
In vitro
tissue
Viral RNA
Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 167–176
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-sars-cov-2-cell-culture A single addition of ivermectin to SARS-CoV-2-infected Vero-hSLAM cells two hours after infection produced approximately a five thousand fold reduction in viral RNA at forty-eight hours. Model/species: Vero-hSLAM cell culture Tissue/system: Viral RNA Exposure: Single ivermectin addition two hours post infection Route: In vitro Duration: 48 hours Limits: This is a cell-culture result in a monkey kidney line, and the authors state only that it warrants further investigation for possible benefits in humans. The concentration relationship to human plasma exposure is not addressed in the report and remains unresolved here. Primary reference: The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. (2020). https://pubmed.ncbi.nlm.nih.gov/32251768/ DOI: 10.1016/j.antiviral.2020.104787 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
Complete structured claim and evidence
Ivermectin increased intracellular chloride concentration and cell size in leukemia cells, accompanied by plasma membrane hyperpolarisation without a change in mitochondrial membrane potential.
Ivermectin → Intracellular chloride concentration in leukemia cells source_derived_draftungraded
Experimental context and source evidence
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
exposure
Low micromolar ivermectin
limitations
The mitochondrial membrane potential was explicitly unchanged, which separates this from mechanisms that act through mitochondrial depolarisation.
organism
Acute myeloid leukemia cell lines and primary patient samples
plain_language
Ivermectin increased intracellular chloride concentration and cell size in leukemia cells, accompanied by plasma membrane hyperpolarisation without a change in mitochondrial membrane potential.
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
tissue
Chloride flux and membrane potential
Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 178–187
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-chloride-influx Ivermectin increased intracellular chloride concentration and cell size in leukemia cells, accompanied by plasma membrane hyperpolarisation without a change in mitochondrial membrane potential. Model/species: Acute myeloid leukemia cell lines and primary patient samples Tissue/system: Chloride flux and membrane potential Exposure: Low micromolar ivermectin Route: In vitro Duration: Not stated here Limits: The mitochondrial membrane potential was explicitly unchanged, which separates this from mechanisms that act through mitochondrial depolarisation. 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.
Complete structured claim and evidence
Ivermectin increased reactive oxygen species generation in leukemia cells, and that increase was functionally required for ivermectin-induced cell death.
Ivermectin → Reactive oxygen species source_derived_draftungraded
Experimental context and source evidence
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.
Complete structured claim and evidence
Ivermectin inhibited the expression of WNT-TCF target genes and repressed C-terminal beta-catenin phosphoforms and CYCLIN D1 in a manner sensitive to okadaic acid, indicating that protein phosphatases are involved.
Ivermectin → WNT-TCF target gene expression source_derived_draftungraded
Experimental context and source evidence
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 cancer cell lines and xenografts
exposure
Ivermectin, with low-concentration effects rescued by direct activation with TCF-VP16
limitations
In vivo inhibition was selective for TCF-dependent xenografts and absent in TCF-independent ones, which supports pathway specificity but does not establish the molecular binding partner.
organism
Human cancer cell lines and xenografts
plain_language
Ivermectin inhibited the expression of WNT-TCF target genes and repressed C-terminal beta-catenin phosphoforms and CYCLIN D1 in a manner sensitive to okadaic acid, indicating that protein phosphatases are involved.
primary_references
The river blindness drug Ivermectin and related macrocyclic lactones inhibit WNT-TCF pathway responses in human cancer. (2014). https://pubmed.ncbi.nlm.nih.gov/25143352/ DOI: 10.15252/emmm.201404084
route
In vitro and in vivo xenograft
tissue
Canonical WNT-TCF signalling output
Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 200–209
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-wnt-tcf-blockade Ivermectin inhibited the expression of WNT-TCF target genes and repressed C-terminal beta-catenin phosphoforms and CYCLIN D1 in a manner sensitive to okadaic acid, indicating that protein phosphatases are involved. Model/species: Human cancer cell lines and xenografts Tissue/system: Canonical WNT-TCF signalling output Exposure: Ivermectin, with low-concentration effects rescued by direct activation with TCF-VP16 Route: In vitro and in vivo xenograft Duration: Not stated here Limits: In vivo inhibition was selective for TCF-dependent xenografts and absent in TCF-independent ones, which supports pathway specificity but does not establish the molecular binding partner. Primary reference: The river blindness drug Ivermectin and related macrocyclic lactones inhibit WNT-TCF pathway responses in human cancer. (2014). https://pubmed.ncbi.nlm.nih.gov/25143352/ DOI: 10.15252/emmm.201404084 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
Complete structured claim and evidence
Ivermectin decreased PAK1 through ubiquitination-mediated degradation, lowering Akt phosphorylation and blocking Akt/mTOR signalling, which produced cytostatic autophagy in breast cancer cells.
Ivermectin → P21-activated kinase 1 / PAK1 source_derived_draftungraded
Experimental context and source evidence
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 breast cancer cells and breast cancer xenografts
exposure
Ivermectin
limitations
The autophagy described is cytostatic and associated with suppressed tumour growth rather than cytotoxic killing.
organism
Human breast cancer cells and breast cancer xenografts
plain_language
Ivermectin decreased PAK1 through ubiquitination-mediated degradation, lowering Akt phosphorylation and blocking Akt/mTOR signalling, which produced cytostatic autophagy in breast cancer cells.
primary_references
Ivermectin Induces Cytostatic Autophagy by Blocking the PAK1/Akt Axis in Breast Cancer. (2016). https://pubmed.ncbi.nlm.nih.gov/27302166/ DOI: 10.1158/0008-5472.CAN-15-2887
route
In vitro and in vivo xenograft
tissue
PAK1 abundance, Akt phosphorylation and autophagy
Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 211–220
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-pak1-akt-autophagy Ivermectin decreased PAK1 through ubiquitination-mediated degradation, lowering Akt phosphorylation and blocking Akt/mTOR signalling, which produced cytostatic autophagy in breast cancer cells. Model/species: Human breast cancer cells and breast cancer xenografts Tissue/system: PAK1 abundance, Akt phosphorylation and autophagy Exposure: Ivermectin Route: In vitro and in vivo xenograft Duration: Not stated here Limits: The autophagy described is cytostatic and associated with suppressed tumour growth rather than cytotoxic killing. Primary reference: Ivermectin Induces Cytostatic Autophagy by Blocking the PAK1/Akt Axis in Breast Cancer. (2016). https://pubmed.ncbi.nlm.nih.gov/27302166/ DOI: 10.1158/0008-5472.CAN-15-2887 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
Complete structured claim and evidence
Avermectin inhibited NF-kappa-B p65 translocation into the nucleus and inhibited JNK and p38 phosphorylation in lipopolysaccharide-stimulated mouse macrophages.
Avermectin → NF-kappa-B p65 nuclear translocation in RAW 264.7 macrophages source_derived_draftungraded
Experimental context and source evidence
duration
30 minutes after lipopolysaccharide
evidence_access
Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
experimental_model
Mouse RAW 264.7 macrophages
exposure
Avermectin 0.625, 1.25 or 5 mg/L for one hour before 1 mg/L lipopolysaccharide
limitations
The compound tested was avermectin, the parent macrocyclic lactone, not ivermectin, and tumour necrosis factor alpha, interleukin-1 beta and interleukin-10 were regulated while interleukin-6 was not significantly affected.
organism
Mouse RAW 264.7 macrophages
plain_language
Avermectin inhibited NF-kappa-B p65 translocation into the nucleus and inhibited JNK and p38 phosphorylation in lipopolysaccharide-stimulated mouse macrophages.
primary_references
Avermectin exerts anti-inflammatory effect by downregulating the nuclear transcription factor kappa-B and mitogen-activated protein kinase activation pathway. (2009). https://pubmed.ncbi.nlm.nih.gov/19453757/ DOI: 10.1111/j.1472-8206.2009.00684.x
route
In vitro
tissue
NF-kappa-B and MAP kinase signalling, cytokine output
Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 222–231
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
## avermectin-nfkb-mapk-inflammation Avermectin inhibited NF-kappa-B p65 translocation into the nucleus and inhibited JNK and p38 phosphorylation in lipopolysaccharide-stimulated mouse macrophages. Model/species: Mouse RAW 264.7 macrophages Tissue/system: NF-kappa-B and MAP kinase signalling, cytokine output Exposure: Avermectin 0.625, 1.25 or 5 mg/L for one hour before 1 mg/L lipopolysaccharide Route: In vitro Duration: 30 minutes after lipopolysaccharide Limits: The compound tested was avermectin, the parent macrocyclic lactone, not ivermectin, and tumour necrosis factor alpha, interleukin-1 beta and interleukin-10 were regulated while interleukin-6 was not significantly affected. Primary reference: Avermectin exerts anti-inflammatory effect by downregulating the nuclear transcription factor kappa-B and mitogen-activated protein kinase activation pathway. (2009). https://pubmed.ncbi.nlm.nih.gov/19453757/ DOI: 10.1111/j.1472-8206.2009.00684.x Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
Complete structured claim and evidence
Topical ivermectin 1% cream was an effective treatment for moderate-to-severe papulopustular rosacea and was more effective than topical metronidazole at twelve weeks, with a number needed to treat of 10.5.
Ivermectin → Inflammatory lesions of papulopustular rosacea source_derived_draftungraded
Experimental context and source evidence
duration
12 weeks, with extension to 36 weeks for relapse
evidence_access
Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
experimental_model
Humans with moderate-to-severe papulopustular rosacea
exposure
Topical ivermectin 1% cream
limitations
Relapse after discontinuation was common in both arms, 62.7% with ivermectin and 68.4% with metronidazole by week 36, and ivermectin has only been tested in moderate-to-severe disease.
organism
Humans with moderate-to-severe papulopustular rosacea
plain_language
Topical ivermectin 1% cream was an effective treatment for moderate-to-severe papulopustular rosacea and was more effective than topical metronidazole at twelve weeks, with a number needed to treat of 10.5.
primary_references
Topical Ivermectin in the Treatment of Papulopustular Rosacea: A Systematic Review of Evidence and Clinical Guideline Recommendations. (2018). https://pubmed.ncbi.nlm.nih.gov/29943217/ DOI: 10.1007/s13555-018-0249-y
route
Topical
tissue
Inflammatory facial lesions, with acaricidal activity against Demodex mites
Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 233–242
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-rosacea-lesions Topical ivermectin 1% cream was an effective treatment for moderate-to-severe papulopustular rosacea and was more effective than topical metronidazole at twelve weeks, with a number needed to treat of 10.5. Model/species: Humans with moderate-to-severe papulopustular rosacea Tissue/system: Inflammatory facial lesions, with acaricidal activity against Demodex mites Exposure: Topical ivermectin 1% cream Route: Topical Duration: 12 weeks, with extension to 36 weeks for relapse Limits: Relapse after discontinuation was common in both arms, 62.7% with ivermectin and 68.4% with metronidazole by week 36, and ivermectin has only been tested in moderate-to-severe disease. Primary reference: Topical Ivermectin in the Treatment of Papulopustular Rosacea: A Systematic Review of Evidence and Clinical Guideline Recommendations. (2018). https://pubmed.ncbi.nlm.nih.gov/29943217/ DOI: 10.1007/s13555-018-0249-y Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
Complete structured claim and evidence
DIM increased MDR1/ABCB1 expression in a PXR-dependent manner.
Human pregnane X receptor / SXR / PXR / NR1I2 → Human P-glycoprotein / ABCB1 / MDR1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/25542144.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d", "start_char": 0, "end_char": 1440, "text_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d"}
experimental_model
Promoter reporters, expression, knockdown and transport assays
exposure
DIM exposure with PXR inhibition or knockdown controls
limitations
Cell-model induction, not a quantified human interaction. Older liver-slice assays showed little CYP3A4 response under their conditions.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human hepatocytes and intestinal cell models
plain_language
The same exposure can change a transporter as well as an enzyme.
primary_references
[dim-p25542144] Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. (2015). https://pubmed.ncbi.nlm.nih.gov/25542144/ DOI: 10.1016/j.toxlet.2014.12.015
tissue_or_cell_type
PXR-regulated CYP3A4 and ABCB1
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 519–530
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Promoter reporters, expression, knockdown and transport assays · source_derived_draft · unverified_draft
### dim-pxr-abcb1 DIM increased MDR1/ABCB1 expression in a PXR-dependent manner. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same exposure can change a transporter as well as an enzyme. organism: Human hepatocytes and intestinal cell models tissue_or_cell_type: PXR-regulated CYP3A4 and ABCB1 experimental_model: Promoter reporters, expression, knockdown and transport assays limitations: Cell-model induction, not a quantified human interaction. Older liver-slice assays showed little CYP3A4 response under their conditions. exposure: DIM exposure with PXR inhibition or knockdown controls evidence_span: {"source_cache": "artifacts/dim-research/25542144.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d", "start_char": 0, "end_char": 1440, "text_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d"} [dim-p25542144] Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. (2015). https://pubmed.ncbi.nlm.nih.gov/25542144/ DOI: 10.1016/j.toxlet.2014.12.015
Complete structured claim and evidence
PXR knockdown or inhibition attenuated DIM-induced ABCB1 expression.
Human pregnane X receptor / SXR / PXR / NR1I2 → Human P-glycoprotein / ABCB1 / MDR1 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/dim-research/25542144.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d", "start_char": 0, "end_char": 1440, "text_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d"}
experimental_model
Promoter reporters, expression, knockdown and transport assays
exposure
DIM exposure with PXR inhibition or knockdown controls
limitations
Cell-model induction, not a quantified human interaction. Older liver-slice assays showed little CYP3A4 response under their conditions.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human hepatocytes and intestinal cell models
plain_language
The response weakened when a required signaling component was blocked.
primary_references
[dim-p25542144] Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. (2015). https://pubmed.ncbi.nlm.nih.gov/25542144/ DOI: 10.1016/j.toxlet.2014.12.015
tissue_or_cell_type
PXR-regulated CYP3A4 and ABCB1
trigger_kind
machinery_impairment Imported condition classification; unverified.
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 558–569
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Promoter reporters, expression, knockdown and transport assays · source_derived_draft · unverified_draft
### dim-pxr-loss-abcb1 PXR knockdown or inhibition attenuated DIM-induced ABCB1 expression. Condition category: machinery_impairment nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The response weakened when a required signaling component was blocked. organism: Human hepatocytes and intestinal cell models tissue_or_cell_type: PXR-regulated CYP3A4 and ABCB1 experimental_model: Promoter reporters, expression, knockdown and transport assays limitations: Cell-model induction, not a quantified human interaction. Older liver-slice assays showed little CYP3A4 response under their conditions. exposure: DIM exposure with PXR inhibition or knockdown controls evidence_span: {"source_cache": "artifacts/dim-research/25542144.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d", "start_char": 0, "end_char": 1440, "text_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d"} [dim-p25542144] Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. (2015). https://pubmed.ncbi.nlm.nih.gov/25542144/ DOI: 10.1016/j.toxlet.2014.12.015
Complete structured claim and evidence
P-glycoprotein overexpression also implicated ABCB1 in export of intracellular sulforaphane/conjugate pools.
Human P-glycoprotein / ABCB1 / MDR1 → Sulforaphane/glutathione-conjugate efflux source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/sulforaphane-research/11988104.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5759bc0af52a1e906602549a3920ebba5641d09b63cc87f0dc61ea8efcb724a9", "start_char": 0, "end_char": 1567, "text_sha256": "5759bc0af52a1e906602549a3920ebba5641d09b63cc87f0dc61ea8efcb724a9"}
experimental_model
Transporter-overexpression and temperature/inhibitor experiments
exposure
Sulforaphane loading; ABCC1 or ABCB1 expression
limitations
Cancer-cell transport experiments; not a measured clinical drug interaction.
nutrient_topic
Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study
organism
Human HL60 leukemia and 8226 myeloma cells
plain_language
The measured pool can be influenced by more than one transporter.
primary_references
[sulforaphane-p11988104] High cellular accumulation of sulphoraphane, a dietary anticarcinogen, is followed by rapid transporter-mediated export as a glutathione conjugate. (2002). https://pubmed.ncbi.nlm.nih.gov/11988104/ DOI: 10.1042/bj3640301
tissue_or_cell_type
Intracellular retention and export
Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 320–331
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transporter-overexpression and temperature/inhibitor experiments · source_derived_draft · unverified_draft
### sulforaphane-abcb1-efflux P-glycoprotein overexpression also implicated ABCB1 in export of intracellular sulforaphane/conjugate pools. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: The measured pool can be influenced by more than one transporter. organism: Human HL60 leukemia and 8226 myeloma cells tissue_or_cell_type: Intracellular retention and export experimental_model: Transporter-overexpression and temperature/inhibitor experiments limitations: Cancer-cell transport experiments; not a measured clinical drug interaction. exposure: Sulforaphane loading; ABCC1 or ABCB1 expression evidence_span: {"source_cache": "artifacts/sulforaphane-research/11988104.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5759bc0af52a1e906602549a3920ebba5641d09b63cc87f0dc61ea8efcb724a9", "start_char": 0, "end_char": 1567, "text_sha256": "5759bc0af52a1e906602549a3920ebba5641d09b63cc87f0dc61ea8efcb724a9"} [sulforaphane-p11988104] High cellular accumulation of sulphoraphane, a dietary anticarcinogen, is followed by rapid transporter-mediated export as a glutathione conjugate. (2002). https://pubmed.ncbi.nlm.nih.gov/11988104/ DOI: 10.1042/bj3640301
Complete structured claim and evidence
The three product extracts inhibited P-glycoprotein transport activity more potently than pure lovastatin in the study assay.
LipoCol Forte, Xuezhikang and Cholestin extract panel studied in 2012 → Human P-glycoprotein / ABCB1 / MDR1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text PMC3513969
experimental_model
Canine MDCK cells engineered with human MDR1; radiolabeled digoxin probe.
limitations
Human transporter in a canine host cell; not a clinical digoxin-interaction magnitude.
nutrient_topic
Red yeast rice collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Red yeast rice
plain_language
An efflux transporter provides another exposure-related route.
primary_references
[23227093] Interaction between Red Yeast Rice and CYP450 Enzymes/P-Glycoprotein and Its Implication for the Clinical Pharmacokinetics of Lovastatin. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23227093/ · DOI 10.1155/2012/127043
Red yeast rice: constituents, mevalonate, CoQ and product-specific interactions (2026-09-20) · lines 132–138
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Canine MDCK cells engineered with human MDR1; radiolabeled digoxin probe. · source_derived_draft · unverified_draft
## red-yeast-rice-extract-pgp An efflux transporter provides another exposure-related route. The three product extracts inhibited P-glycoprotein transport activity more potently than pure lovastatin in the study assay. Model: Canine MDCK cells engineered with human MDR1; radiolabeled digoxin probe. Limitations: Human transporter in a canine host cell; not a clinical digoxin-interaction magnitude. Evidence access: Primary full text PMC3513969 [23227093] Interaction between Red Yeast Rice and CYP450 Enzymes/P-Glycoprotein and Its Implication for the Clinical Pharmacokinetics of Lovastatin. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23227093/ · DOI 10.1155/2012/127043
Complete structured claim and evidence
OCT1/ABCB1 double-transfected cells transported berberine basolaterally to apically faster than single transfectants; zosuquidar inhibited apical efflux.
Human P-glycoprotein / ABCB1 / MDR1 → Berberine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/18157518.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "34651ed2e9ce3c38b6042e616b5c36d932fe6f1099c627d1b5403b338eae7b2b", "start_char": 0, "end_char": 1918, "text_sha256": "34651ed2e9ce3c38b6042e616b5c36d932fe6f1099c627d1b5403b338eae7b2b"}
experimental_model
Polarized transporter-transfected MDCKII cells
exposure
Berberine transport kinetics and transporter inhibition
limitations
Engineered system, not direct evidence for human oral bioavailability or a universal transport bottleneck.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Human OCT1, OCT2 and ABCB1 in engineered canine cells
plain_language
An entry transporter and an exit pump can work in sequence.
primary_references
[berberine-p18157518] Vectorial transport of the plant alkaloid berberine by double-transfected cells expressing the human organic cation transporter 1 (OCT1, SLC22A1) and the efflux pump MDR1 P-glycoprotein (ABCB1). (2008). https://pubmed.ncbi.nlm.nih.gov/18157518/ DOI: 10.1007/s00210-007-0219-x
tissue_or_cell_type
Basolateral uptake and apical export
transport_effect
lowers Basolateral-to-apical flux exceeded absorptive flux and zosuquidar inhibited the apical efflux, so the step removes berberine from the cell.
transport_pool
the enterocyte interior Basolateral-to-apical flux exceeded absorptive flux and zosuquidar inhibited the apical efflux, so the step removes berberine from the cell.
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 233–244
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Polarized transporter-transfected MDCKII cells · source_derived_draft · unverified_draft
### berberine-abcb1-efflux OCT1/ABCB1 double-transfected cells transported berberine basolaterally to apically faster than single transfectants; zosuquidar inhibited apical efflux. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: An entry transporter and an exit pump can work in sequence. organism: Human OCT1, OCT2 and ABCB1 in engineered canine cells tissue_or_cell_type: Basolateral uptake and apical export experimental_model: Polarized transporter-transfected MDCKII cells limitations: Engineered system, not direct evidence for human oral bioavailability or a universal transport bottleneck. exposure: Berberine transport kinetics and transporter inhibition evidence_span: {"source_cache": "artifacts/berberine-research/18157518.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "34651ed2e9ce3c38b6042e616b5c36d932fe6f1099c627d1b5403b338eae7b2b", "start_char": 0, "end_char": 1918, "text_sha256": "34651ed2e9ce3c38b6042e616b5c36d932fe6f1099c627d1b5403b338eae7b2b"} [berberine-p18157518] Vectorial transport of the plant alkaloid berberine by double-transfected cells expressing the human organic cation transporter 1 (OCT1, SLC22A1) and the efflux pump MDR1 P-glycoprotein (ABCB1). (2008). https://pubmed.ncbi.nlm.nih.gov/18157518/ DOI: 10.1007/s00210-007-0219-x
Complete structured claim and evidence
Berberine increased MDR1/ABCB1 expression; Nrf2 silencing abolished the gene response in Caco-2 cells.
Berberine → Human P-glycoprotein / ABCB1 / MDR1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/29891588.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e59ba2b3b6e505cf3b220d32040e37f53553ea73427dd522cf7ea237d7d0f405", "start_char": 0, "end_char": 1752, "text_sha256": "e59ba2b3b6e505cf3b220d32040e37f53553ea73427dd522cf7ea237d7d0f405"}
experimental_model
Nrf2 reporter, gene silencing and expression assays
exposure
Berberine concentration and time response
limitations
Transporter expression after prolonged exposure is not the same endpoint as acute competitive inhibition. Rat colitis improvement does not establish human IBD efficacy.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Human Caco-2 cells; rat colitis in a separate arm
plain_language
Repeated exposure can increase the pump that exports drugs.
primary_references
[berberine-p29891588] Berberine Upregulates P-Glycoprotein in Human Caco-2 Cells and in an Experimental Model of Colitis in the Rat via Activation of Nrf2-Dependent Mechanisms. (2018). https://pubmed.ncbi.nlm.nih.gov/29891588/ DOI: 10.1124/jpet.118.249615
tissue_or_cell_type
Nrf2-dependent ABCB1 expression
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 545–556
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Nrf2 reporter, gene silencing and expression assays · source_derived_draft · unverified_draft
### berberine-abcb1-expression Berberine increased MDR1/ABCB1 expression; Nrf2 silencing abolished the gene response in Caco-2 cells. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Repeated exposure can increase the pump that exports drugs. organism: Human Caco-2 cells; rat colitis in a separate arm tissue_or_cell_type: Nrf2-dependent ABCB1 expression experimental_model: Nrf2 reporter, gene silencing and expression assays limitations: Transporter expression after prolonged exposure is not the same endpoint as acute competitive inhibition. Rat colitis improvement does not establish human IBD efficacy. exposure: Berberine concentration and time response evidence_span: {"source_cache": "artifacts/berberine-research/29891588.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e59ba2b3b6e505cf3b220d32040e37f53553ea73427dd522cf7ea237d7d0f405", "start_char": 0, "end_char": 1752, "text_sha256": "e59ba2b3b6e505cf3b220d32040e37f53553ea73427dd522cf7ea237d7d0f405"} [berberine-p29891588] Berberine Upregulates P-Glycoprotein in Human Caco-2 Cells and in an Experimental Model of Colitis in the Rat via Activation of Nrf2-Dependent Mechanisms. (2018). https://pubmed.ncbi.nlm.nih.gov/29891588/ DOI: 10.1124/jpet.118.249615
Complete structured claim and evidence
Berberine basolateral-to-apical flux exceeded absorptive flux by approximately 30-fold; P-glycoprotein substrates inhibited the secretory flux.
Human P-glycoprotein / ABCB1 / MDR1 → Berberine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/12434406.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "489bc53e580f5a13cf3320ba724b6e83572a9f71f9eee9c2f1b255d7ebd26be2", "start_char": 0, "end_char": 1594, "text_sha256": "489bc53e580f5a13cf3320ba724b6e83572a9f71f9eee9c2f1b255d7ebd26be2"}
experimental_model
Bidirectional transport assays
exposure
Berberine transport and pretreatment
limitations
Caco-2 secretion is not a quantitative human drug-interaction study. Competing substrates implicate P-glycoprotein but do not make every substrate a clinical interaction.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Human Caco-2 cells
plain_language
An intestinal efflux route can limit net absorption in the model.
primary_references
[berberine-p12434406] P-glycoprotein-mediated transport of berberine across Caco-2 cell monolayers. (2002). https://pubmed.ncbi.nlm.nih.gov/12434406/ DOI: 10.1002/jps.10268
tissue_or_cell_type
Intestinal epithelial model
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 246–257
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bidirectional transport assays · source_derived_draft · unverified_draft
### berberine-intestinal-efflux Berberine basolateral-to-apical flux exceeded absorptive flux by approximately 30-fold; P-glycoprotein substrates inhibited the secretory flux. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: An intestinal efflux route can limit net absorption in the model. organism: Human Caco-2 cells tissue_or_cell_type: Intestinal epithelial model experimental_model: Bidirectional transport assays limitations: Caco-2 secretion is not a quantitative human drug-interaction study. Competing substrates implicate P-glycoprotein but do not make every substrate a clinical interaction. exposure: Berberine transport and pretreatment evidence_span: {"source_cache": "artifacts/berberine-research/12434406.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "489bc53e580f5a13cf3320ba724b6e83572a9f71f9eee9c2f1b255d7ebd26be2", "start_char": 0, "end_char": 1594, "text_sha256": "489bc53e580f5a13cf3320ba724b6e83572a9f71f9eee9c2f1b255d7ebd26be2"} [berberine-p12434406] P-glycoprotein-mediated transport of berberine across Caco-2 cell monolayers. (2002). https://pubmed.ncbi.nlm.nih.gov/12434406/ DOI: 10.1002/jps.10268
Complete structured claim and evidence
Tartrazine did not inhibit human P-glycoprotein-mediated rhodamine-123 efflux in the cell assay.
Tartrazine → Human P-glycoprotein / ABCB1 / MDR1 source_derived_draftungraded
Experimental context and source evidence
dose
Tartrazine 0.1-1000 micromolar, rhodamine-123 5 micromolar; GF120918 positive control
duration
1 h at 37 C
evidence_access
Primary full-text methods/results and metadata.
evidence_scope
literature_reviewed; source-specific experimental curation
experimental_model
LLC-MDR1-WT cells expressing recombinant human ABCB1
limitations
Human transporter in a heterologous cell system. Negative P-gp inhibition is not inconsistent with a BCRP effect in a different assay.
nutrient_topic
Tartrazine food-colorant chapter; nutrient, drug and peptide interactions retain their models and limits. · Tartrazine
organism
LLC-MDR1-WT cells expressing recombinant human ABCB1
plain_language
Tartrazine did not inhibit human P-glycoprotein-mediated rhodamine-123 efflux in the cell assay.
primary_references
Food dyes as P-glycoprotein modulators. (2020). https://pubmed.ncbi.nlm.nih.gov/33011351/ DOI: 10.1016/j.fct.2020.111785
route
In vitro co-incubation
tissue
Rhodamine-123 efflux assay
Tartrazine: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 237–246
Original AI-assisted curation of eighteen primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · LLC-MDR1-WT cells expressing recombinant human ABCB1 · source_derived_draft · unverified_draft
## tartrazine-pgp-efflux-null Tartrazine did not inhibit human P-glycoprotein-mediated rhodamine-123 efflux in the cell assay. Model/species: LLC-MDR1-WT cells expressing recombinant human ABCB1 Tissue: Rhodamine-123 efflux assay Exposure: Tartrazine 0.1-1000 micromolar, rhodamine-123 5 micromolar; GF120918 positive control Route: In vitro co-incubation Duration: 1 h at 37 C Limits: Human transporter in a heterologous cell system. Negative P-gp inhibition is not inconsistent with a BCRP effect in a different assay. Primary reference: Food dyes as P-glycoprotein modulators. (2020). https://pubmed.ncbi.nlm.nih.gov/33011351/ DOI: 10.1016/j.fct.2020.111785 Access: Primary full-text methods/results and metadata.
Complete structured claim and evidence
Myricetin increased rhodamine-123 accumulation in P-glycoprotein-overexpressing human MCF-7/ADR cells.
Myricetin → Human P-glycoprotein / ABCB1 / MDR1 supersededungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Drug-resistant human breast-cell model.
limitations
Functional probe result, not proof of selective direct binding or human intestinal inhibition.
nutrient_topic
Myricetin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Myricetin
plain_language
Less export can increase intracellular probe retention.
primary_references
Effects of myricetin on the bioavailability of carvedilol in rats. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22132944/ · DOI 10.3109/13880209.2011.611141
Myricetin: metabolism, immune signaling, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 236–242
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Drug-resistant human breast-cell model. · source_derived_draft · unverified_draft
## myricetin-pgp-efflux Less export can increase intracellular probe retention. Myricetin increased rhodamine-123 accumulation in P-glycoprotein-overexpressing human MCF-7/ADR cells. Model: Drug-resistant human breast-cell model. Limitations: Functional probe result, not proof of selective direct binding or human intestinal inhibition. Evidence access: Primary abstract Effects of myricetin on the bioavailability of carvedilol in rats. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22132944/ · DOI 10.3109/13880209.2011.611141
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.

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.

Berberine: metabolism, nutrient connections and drug 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
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug 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
Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22)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. · unverified_draftRead preserved source
Myricetin: metabolism, immune signaling, redox chemistry and cross-nutrient mechanisms (2026-09-19)AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · unverified_draftRead preserved source
Red yeast rice: constituents, mevalonate, CoQ and product-specific interactions (2026-09-20)AI-assisted research curation; primary references, access levels and experimental limitations individually identified. 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
Tartrazine: mechanisms, molecular forms and cross-actor connections (2026-09-20)Original AI-assisted curation of eighteen primary studies. Study-specific citations, negative findings and limitations retained. 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.

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.

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

Ivermectin

The mechanisms

An avermectin-sensitive glutamate-gated chloride channel was cloned from Caenorhabditis elegans and shown to be a new member of the ligand-gated ion channel superfamily.

Ivermectin binds in the transmembrane domain of the Caenorhabditis elegans glutamate-gated chloride channel and stabilises an open-pore conformation.

Ivermectin exposure decreased the amount of protein released from the excretory-secretory apparatus of Brugia malayi microfilariae.

Ivermectin had little direct effect on Brugia malayi microfilariae in culture at pharmacologically relevant concentrations.

Mice lacking the mdr1a P-glycoprotein gene showed about one hundred fold increased sensitivity to ivermectin, and mdr1a P-glycoprotein was the major P-glycoprotein of the blood-brain barrier.

Ivermectin accumulated thirty-six to sixty fold in the brain of mdr1a,b knockout mice compared with wild type, while selamectin accumulated only five to ten fold.

Preapplication of ivermectin in the micromolar range strongly enhanced the acetylcholine-evoked current of alpha7 nicotinic acetylcholine receptors, acting as a positive allosteric effector.

Ivermectin was a specific positive allosteric effector of heterologously expressed P2X4 channels with an EC50 near 250 nanomolar, increasing current amplitude and slowing deactivation.

Ivermectin produced no significant effect on fast ATP-evoked inward currents in adult trigeminal mesencephalic nucleus or hippocampal CA1 neurons.

Ivermectin irreversibly activated human alpha1 homomeric and alpha1beta heteromeric glycine receptors at concentrations at or above 0.03 micromolar, through a site that is not the glycine site.

Ivermectin bound the farnesoid X receptor ligand-binding domain and induced its transcriptional activity, with a crystal structure showing a distinct binding mode and an expanded ligand-binding pocket.

Ivermectin decreased serum glucose and cholesterol in wild-type mice but not in FXR-null mice.

Ivermectin inhibited importin alpha/beta-mediated nuclear import broadly, with no effect on a range of other nuclear import pathways including import mediated by importin beta1 alone.

Ivermectin inhibited replication of HIV-1 and dengue virus, both of which depend on importin alpha/beta nuclear import of HIV-1 integrase and dengue NS5 polymerase respectively.

A single addition of ivermectin to SARS-CoV-2-infected Vero-hSLAM cells two hours after infection produced approximately a five thousand fold reduction in viral RNA at forty-eight hours.

Ivermectin increased intracellular chloride concentration and cell size in leukemia cells, accompanied by plasma membrane hyperpolarisation without a change in mitochondrial membrane potential.

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

Ivermectin inhibited the expression of WNT-TCF target genes and repressed C-terminal beta-catenin phosphoforms and CYCLIN D1 in a manner sensitive to okadaic acid, indicating that protein phosphatases are involved.

Ivermectin decreased PAK1 through ubiquitination-mediated degradation, lowering Akt phosphorylation and blocking Akt/mTOR signalling, which produced cytostatic autophagy in breast cancer cells.

Avermectin inhibited NF-kappa-B p65 translocation into the nucleus and inhibited JNK and p38 phosphorylation in lipopolysaccharide-stimulated mouse macrophages.

Topical ivermectin 1% cream was an effective treatment for moderate-to-severe papulopustular rosacea and was more effective than topical metronidazole at twelve weeks, with a number needed to treat of 10.5.

DIM increased MDR1/ABCB1 expression in a PXR-dependent manner.

PXR knockdown or inhibition attenuated DIM-induced ABCB1 expression.

P-glycoprotein overexpression also implicated ABCB1 in export of intracellular sulforaphane/conjugate pools.

The three product extracts inhibited P-glycoprotein transport activity more potently than pure lovastatin in the study assay.

OCT1/ABCB1 double-transfected cells transported berberine basolaterally to apically faster than single transfectants; zosuquidar inhibited apical efflux.

Berberine increased MDR1/ABCB1 expression; Nrf2 silencing abolished the gene response in Caco-2 cells.

Berberine basolateral-to-apical flux exceeded absorptive flux by approximately 30-fold; P-glycoprotein substrates inhibited the secretory flux.

Tartrazine did not inhibit human P-glycoprotein-mediated rhodamine-123 efflux in the cell assay.

Myricetin increased rhodamine-123 accumulation in P-glycoprotein-overexpressing human MCF-7/ADR cells.

Availability and dependencies

The sources

Recorded disagreements

Open questions in this collection