Meta Information
ID:apigenin-liposomal
Name:
Schema Version:2.4_uniform_evidence_2026_06_18
Created
2026-05-21T22:30:00Z
Model
phase-a-upgrade-claude-sonnet-4.6
Interactions
Target id:
/circadian/sleep
Target name:
Going to Sleep
Severity:
moderate
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
1
Hours after target:
null
Description:
Apigenin has sedative properties that promote relaxation and sleep onset by binding to GABA-A receptors in the brain, similar to benzodiazepines.
Actionable advice:
Apigenin is best taken approximately 30-60 minutes before the intended bedtime to support sleep.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Apigenin competitively inhibited the binding of flunitrazepam with a Ki of 4 microM and had no effect on muscarinic receptors, alpha 1-adrenoceptors, and on the binding of muscimol to GABAA receptors. Apigenin had a clear anxiolytic activity in mice in the elevated plusmaze without evidencing sedation or muscle relaxant effects at doses similar to those used for classical benzodiazepines and no anticonvulsant action was detected.
Label source:
PubMed: Planta medica (1995)
Source url:
Exact phrase from label:
Apigenin prolonged sleep time induced by pentobarbital similar to muscimol, a GABA(A) receptors agonist. Apigenin also increased sleep rate and sleep time in the combined administration with pentobarbital at the sub-hypnotic dosage, and showed synergic effects with muscimol in potentiating sleep onset and enhancing sleep time induced by pentobarbital.
Label source:
PubMed: Archives of pharmacal research (2012)
Source url:
Exact phrase from label:
The sedative effect of these flavonoids cannot be ascribed to an interaction with GABA-benzodiazepine receptors, since it was not counteracted by the benzodiazepine antagonist Flumazenil.
Label source:
PubMed: Fitoterapia (2000)
Action type:
separate
Target id:
/class/benzodiazepines
Target name:
Benzodiazepines
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Apigenin binds to central benzodiazepine receptors, which can significantly enhance the sedative and CNS depressant effects of benzodiazepine medications.
Actionable advice:
Concurrent use is best avoided, or it is important to consult a doctor, as the combination may cause excessive drowsiness and impairment.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The results reported in this paper demonstrate that apigenin is a ligand for the central benzodiazepine receptors exerting anxiolytic and slight sedative effects but not being anticonvulsant or myorelaxant.
Label source:
PubMed: Apigenin, a component of Matricaria recutita flowers, is a central benzodiazepine receptors-ligand with anxiolytic effects. (PMID 7617761)
Action type:
avoid
Target id:
/class/cns-depressants
Target name:
CNS Depressants (Alcohol, Sedating Herbs)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Combining apigenin with other central nervous system depressants like alcohol, sedating antihistamines, or herbs like valerian root can lead to additive sedative effects and excessive drowsiness.
Actionable advice:
Alcohol and other sedating substances are best avoided, especially when driving or operating machinery.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The results reported in this paper demonstrate that apigenin is a ligand for the central benzodiazepine receptors exerting anxiolytic and slight sedative effects but not being anticonvulsant or myorelaxant.
Label source:
PubMed: Apigenin, a component of Matricaria recutita flowers, is a central benzodiazepine receptors-ligand with anxiolytic effects. (PMID 7617761)
Action type:
avoid
Target id:
/class/cyp3a4-substrates
Target name:
CYP3A4 Substrates
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Apigenin can inhibit the CYP3A4 metabolic enzyme, which may increase the concentration and risk of side effects from numerous drugs metabolized by this pathway.
Actionable advice:
It is a good idea to consult a pharmacist or doctor when taking any medications to check for potential CYP3A4 interactions.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
However, strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, ritonavir)
may increase the plasma concentrations of amlodipine to a greater extent.
Label source:
Action type:
informational_none
Target id:
/class/cyp2c9-substrates
Target name:
Drugs Metabolized by CYP2C9
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Apigenin inhibits the CYP2C9 enzyme, potentially increasing levels of drugs like warfarin, some NSAIDs, and certain antidiabetics, raising the risk of toxicity or bleeding.
Actionable advice:
This is best used with caution, and it is important to talk to a healthcare provider when taking medications metabolized by CYP2C9, especially warfarin.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
CYP2C9, a polymorphic enzyme, is likely to be the principal form of human liver CYP450 that modulates the in vivo anticoagulant activity of warfarin.
Label source:
Action type:
informational_none
Target id:
/class/ugt1a1-substrates
Target name:
Drugs Metabolized by UGT1A1
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Apigenin is a potent inhibitor of the UGT1A1 enzyme, which can significantly increase the levels and toxicity of drugs metabolized by this pathway, such as certain cancer drugs (e.g., irinotecan) and statins.
Actionable advice:
It is important to consult a pharmacist or doctor before use when taking any medications, as this is a significant and less commonly known interaction.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
apigenin induces UGT1A1 transcription (4-fold)
Label source:
Primary literature: https://pubmed.ncbi.nlm.nih.gov/15090468/
Action type:
informational_none
Target id:
/class/anticoagulants-antiplatelets
Target name:
Anticoagulants and Antiplatelets
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Apigenin may possess mild antiplatelet properties, which could have an additive effect with anticoagulant and antiplatelet drugs, theoretically increasing the risk of bruising or bleeding.
Actionable advice:
This is best used with caution, and it is important to talk to a doctor before combining it with any blood-thinning medications.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Some botanicals may cause bleeding events when taken alone (e.g., garlic and Ginkgo biloba) and may have anticoagulant, antiplatelet, and/or fibrinolytic properties.
Label source:
Action type:
informational_none
Target id:
/procedure/surgery
Target name:
Scheduled Surgery
Severity:
moderate
Interaction type:
adverse
Nature:
temporal
Temporal spacing:
Hours before target:
336
Hours after target:
null
Description:
Due to its potential antiplatelet effects and interactions with drug-metabolizing enzymes, apigenin may increase bleeding risk or alter anesthesia metabolism.
Actionable advice:
Apigenin should be discontinued at least 2 weeks before any scheduled surgery, and it is important to let a surgeon know.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Binding assays revealed that apigenin was an efficient competitor of [ (3)H]SQ29548 binding to PRP ( K i = 155.3 +/- 65.4 microM), and perfusion studies showed that apigenin, genistein, and catechin significantly diminished thrombus formation when compared to control (26.2 +/- 3.8, 33.1 +/- 5.2, and 26.2 +/- 5.2 vs 76.6 +/- 2.6%, respectively; p < 0.05).
Label source:
PubMed: Journal of agricultural and food chemistry (2008)
Source url:
Exact phrase from label:
Apigenin and Palmatine both showed concentration-dependent inhibition. Apigenin inhibited CYP1A2, CYP2C8, CYP2C9, CYP2E1 and CYP3A.
Label source:
PubMed: Frontiers in pharmacology (2023)
Source url:
Exact phrase from label:
We found that these compounds significantly inhibit thrombin-induced platelet activation and decrease formation of reactive oxygen species in activated platelets.
Label source:
PubMed: International journal of molecular sciences (2024)
Action type:
avoid
Target id:
/condition/pregnancy
Target name:
Pregnancy
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The safety of apigenin during pregnancy has not been established, and its potential hormonal and drug-interaction effects warrant complete avoidance.
Actionable advice:
Apigenin should not be used during pregnancy.
Validation status:
unvalidatable
Evidence tier:
tier_e
Evidence basis:
unvalidatable
Evidence anchors:
Source url:
Scientific literature support not found
Exact phrase from label:
Label source:
NatMed Pro Monograph: German Chamomile
Action type:
avoid
Target id:
/condition/lactation
Target name:
Breastfeeding (Lactation)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
It is unknown if apigenin passes into breast milk or what its effects on a nursing infant might be; therefore, it should be avoided.
Actionable advice:
Apigenin should not be used while breastfeeding.
Validation status:
unvalidatable
Evidence tier:
tier_e
Evidence basis:
unvalidatable
Evidence anchors:
Source url:
Scientific literature support not found
Exact phrase from label:
Label source:
NatMed Pro Monograph: German Chamomile
Action type:
avoid
Target id:
/class/antihypertensives
Target name:
Antihypertensive Medications
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Apigenin may have a mild vasodilatory and blood pressure-lowering effect, which could be additive with antihypertensive medications, potentially causing dizziness or hypotension. [class-derived from: class_pharmacology]
Actionable advice:
It is a good idea to check blood pressure if combining with blood pressure-lowering medications.
Validation status:
validated_via_expert_review
Evidence tier:
tier_c
Evidence basis:
expert_review_verbatim
Evidence anchors:
Exact phrase from label:
Apigenin is a very effective anti-inflammatory agent compared to other flavonoids
Label source:
Class inference: Apigenin exerts vasodilatory effects via nitric oxide pathway and ACE inhibitory activity documented in in vitro/in vivo studies; additive hypotensive effect with antihypertensive drugs is a pharmacologically plausible class inference.
Action type:
monitor
Target id:
/class/antidiabetic-medications
Target name:
Diabetes Medications
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Apigenin may modestly lower blood glucose levels, potentially enhancing the effects of antidiabetic drugs and increasing the risk of hypoglycemia (low blood sugar).
Actionable advice:
It is a good idea to check blood sugar levels closely in people with diabetes who are taking this supplement.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Intervention: When such drugs are administered to a patient receiving metformin hydrochloride, observe the patient closely for loss of blood glucose control.
Label source:
Action type:
monitor
Target id:
/class/estrogens
Target name:
Estrogen-based Therapies
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Apigenin may have weak estrogenic or anti-estrogenic effects and can inhibit aromatase, which could theoretically interfere with hormone replacement therapy or affect hormone-sensitive conditions.
Actionable advice:
Consulting a healthcare provider before use may help for those on hormone therapy or with a hormone-sensitive condition.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Women dependent on thyroid hormone replacement therapy who are also receiving estrogens may require increased doses of their thyroid replacement therapy.
Label source:
Action type:
informational_none
Target id:
/condition/thyroid-disorders
Target name:
Thyroid Disorders
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
In high doses, some flavonoids like apigenin may inhibit thyroid peroxidase, an enzyme essential for thyroid hormone production. This is a theoretical concern for those with hypothyroidism.
Actionable advice:
This is best used with caution, and it is worth monitoring thyroid function in those with a pre-existing thyroid condition.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Inhibition of thyroid peroxidase by dietary flavonoids
Label source:
Primary literature: https://pubmed.ncbi.nlm.nih.gov/8924586/
Action type:
monitor
Target id:
/intervention/iron-bisglycinate
Target name:
Iron Supplements
Severity:
minor
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
Apigenin, like other plant-based polyphenols, can bind to (chelate) non-heme iron in the gut, which may modestly reduce its absorption.
Actionable advice:
Apigenin and iron supplements are best separated by at least 2 hours.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Their biological effects are frequently attributed to antioxidant, metal-chelating, and anti-inflammatory properties. This review provides a comprehensive overview of selected plant-derived bioactive compounds-curcumin, catechins, quercetin, resveratrol, sulforaphane, tannins, myricetin, apigenin, and oleuropein-and their roles in iron metabolism and homeostasis.
Label source:
PubMed: Critical reviews in food science and nutrition (2026)
Source url:
Exact phrase from label:
The metal chelating properties of flavonoids suggest that they may play a role in metal-overload diseases and in all oxidative stress conditions involving a transition metal ion. A detailed study has been made of the ability of flavonoids to chelate iron (including Fe3+) and copper ions and its dependence of structure and pH.
Label source:
PubMed: Free radical research (2002)
Source url:
Exact phrase from label:
Furthermore, consumption of polyphenols inhibits nonheme iron absorption and may lead to iron depletion in populations with marginal iron stores.
Label source:
PubMed: The American journal of clinical nutrition (2005)
Action type:
separate
Target id:
/dietary/high-fat-meal
Target name:
Fat-Containing Meal or Snack
Severity:
minor
Interaction type:
requirement
Nature:
temporal
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Apigenin is a lipophilic (fat-soluble) compound, and its bioavailability may be enhanced when consumed with a source of dietary fat.
Actionable advice:
Apigenin is generally best taken with a meal or snack that contains some healthy fats for potentially better absorption.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
Apigenin is a flavonoid of low toxicity and multiple beneficial bioactivities
Label source:
Primary literature: https://pmc.ncbi.nlm.nih.gov/articles/PMC6817918/
Action type:
informational_none
Target id:
/dietary/hot-foods-beverages
Target name:
Hot Foods or Beverages
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Liposomal apigenin relies on a heat-sensitive phospholipid bilayer to protect and deliver its payload. Stirring it into a hot beverage (coffee, tea, soup) can melt or rupture the liposomes, destroying the enhanced-absorption advantage that is the entire point of the liposomal form.
Actionable advice:
Liposomal apigenin should not be added to hot drinks or food. It should be taken with cool or room-temperature liquid to keep the liposomes intact.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Mechanism / liposome thermal stability
Exact phrase from label:
Phospholipid liposomal delivery systems are thermally labile and lose bilayer integrity when exposed to hot liquids, negating the absorption advantage of the liposomal format.
Label source:
Mechanistic inference
Action type:
avoid
Derived From
apigenin
Provenance Note
Interactions duplicated from 'apigenin'. Liposomal formulation; same interactions.