Nutrient chapter

Graviola / Annona muricata

Annona muricata (soursop/graviola), a botanical whose fruit, juice, leaves, seeds, teas and extracts have different compositions. Whole-plant effects are not interchangeable with purified annonacin.

10 recorded mechanisms · 1 availability situations · 1 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.

  1. The commercial Annona muricata juice used in the chronic mouse study contained 16.2 mg/L annonacin plus other acetogenins and 41 measured isoquinoline alkaloids.

    Commercial soursop juice used in the 2016 chronic mouse study → Annonacin source_derived_draftungraded
    Experimental context and source evidence
    dose
    Study juice provided as drinking fluid
    duration
    Juice lot used for 12-month exposure
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    evidence_scope
    literature_reviewed; model-specific source-derived curation
    experimental_model
    Analyzed commercial soursop juice
    limitations
    One product lot does not define every fruit, juice, leaf tea or supplement; the mixture contained many candidate actors.
    nutrient_topic
    Graviola (Annona muricata) chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Graviola / Annona muricata
    organism
    Analyzed commercial soursop juice
    plain_language
    The commercial Annona muricata juice used in the chronic mouse study contained 16.2 mg/L annonacin plus other acetogenins and 41 measured isoquinoline alkaloids.
    primary_references
    Chronic consumption of Annona muricata juice triggers and aggravates cerebral tau phosphorylation in wild-type and MAPT transgenic mice. (2016). https://pubmed.ncbi.nlm.nih.gov/27569447/ DOI: 10.1111/jnc.13835
    route
    Food-composition analysis
    tissue
    HPLC-MS constituent analysis

    Graviola (Annona muricata): mechanism of action and interactions (2026-09-20) · lines 11–20

    Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Analyzed commercial soursop juice · source_derived_draft · unverified_draft

    ## graviola-juice-composition The commercial Annona muricata juice used in the chronic mouse study contained 16.2 mg/L annonacin plus other acetogenins and 41 measured isoquinoline alkaloids. Model/species: Analyzed commercial soursop juice Tissue/system: HPLC-MS constituent analysis Exposure: Study juice provided as drinking fluid Route: Food-composition analysis Duration: Juice lot used for 12-month exposure Limits: One product lot does not define every fruit, juice, leaf tea or supplement; the mixture contained many candidate actors. Primary reference: Chronic consumption of Annona muricata juice triggers and aggravates cerebral tau phosphorylation in wild-type and MAPT transgenic mice. (2016). https://pubmed.ncbi.nlm.nih.gov/27569447/ DOI: 10.1111/jnc.13835 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    Complete structured claim and evidence

  2. Twelve months of the analyzed soursop juice increased somatodendritic phosphorylated-tau-positive neurons, most strongly in R406W-MAPT mice and less in wild-type-tau or non-transgenic mice.

    Commercial soursop juice used in the 2016 chronic mouse study → Somatodendritic phosphorylated tau in mouse brain source_derived_draftungraded
    Experimental context and source evidence
    dose
    Commercial soursop juice as drinking fluid
    duration
    12 months
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    evidence_scope
    literature_reviewed; model-specific source-derived curation
    experimental_model
    Non-transgenic, human-wild-type-MAPT and R406W-MAPT mice
    limitations
    The multi-constituent juice and transgenic susceptibility prevent assignment to annonacin alone or direct prediction of human risk magnitude.
    nutrient_topic
    Graviola (Annona muricata) chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Graviola / Annona muricata
    organism
    Non-transgenic, human-wild-type-MAPT and R406W-MAPT mice
    plain_language
    Twelve months of the analyzed soursop juice increased somatodendritic phosphorylated-tau-positive neurons, most strongly in R406W-MAPT mice and less in wild-type-tau or non-transgenic mice.
    primary_references
    Chronic consumption of Annona muricata juice triggers and aggravates cerebral tau phosphorylation in wild-type and MAPT transgenic mice. (2016). https://pubmed.ncbi.nlm.nih.gov/27569447/ DOI: 10.1111/jnc.13835
    route
    Oral
    tissue
    Regional brain phospho-tau histology

    Graviola (Annona muricata): mechanism of action and interactions (2026-09-20) · lines 22–31

    Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Non-transgenic, human-wild-type-MAPT and R406W-MAPT mice · source_derived_draft · unverified_draft

    ## graviola-juice-tau Twelve months of the analyzed soursop juice increased somatodendritic phosphorylated-tau-positive neurons, most strongly in R406W-MAPT mice and less in wild-type-tau or non-transgenic mice. Model/species: Non-transgenic, human-wild-type-MAPT and R406W-MAPT mice Tissue/system: Regional brain phospho-tau histology Exposure: Commercial soursop juice as drinking fluid Route: Oral Duration: 12 months Limits: The multi-constituent juice and transgenic susceptibility prevent assignment to annonacin alone or direct prediction of human risk magnitude. Primary reference: Chronic consumption of Annona muricata juice triggers and aggravates cerebral tau phosphorylation in wild-type and MAPT transgenic mice. (2016). https://pubmed.ncbi.nlm.nih.gov/27569447/ DOI: 10.1111/jnc.13835 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    Complete structured claim and evidence

  3. Chronic soursop juice reduced synaptophysin immunoreactivity and increased 3-nitrotyrosine reactivity across the tested mouse genotypes.

    Commercial soursop juice used in the 2016 chronic mouse study → Mouse brain synaptophysin and nitrotyrosine profile source_derived_draftungraded
    Experimental context and source evidence
    dose
    Commercial soursop juice
    duration
    12 months
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    evidence_scope
    literature_reviewed; model-specific source-derived curation
    experimental_model
    Three mouse tau genotypes
    limitations
    Marker changes are not a direct measure of human neurodegeneration and cannot identify which juice constituent caused them.
    nutrient_topic
    Graviola (Annona muricata) chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Graviola / Annona muricata
    organism
    Three mouse tau genotypes
    plain_language
    Chronic soursop juice reduced synaptophysin immunoreactivity and increased 3-nitrotyrosine reactivity across the tested mouse genotypes.
    primary_references
    Chronic consumption of Annona muricata juice triggers and aggravates cerebral tau phosphorylation in wild-type and MAPT transgenic mice. (2016). https://pubmed.ncbi.nlm.nih.gov/27569447/ DOI: 10.1111/jnc.13835
    route
    Oral
    tissue
    Brain synaptic and nitrative-stress markers

    Graviola (Annona muricata): mechanism of action and interactions (2026-09-20) · lines 33–42

    Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Three mouse tau genotypes · source_derived_draft · unverified_draft

    ## graviola-juice-synapse-nitrotyrosine Chronic soursop juice reduced synaptophysin immunoreactivity and increased 3-nitrotyrosine reactivity across the tested mouse genotypes. Model/species: Three mouse tau genotypes Tissue/system: Brain synaptic and nitrative-stress markers Exposure: Commercial soursop juice Route: Oral Duration: 12 months Limits: Marker changes are not a direct measure of human neurodegeneration and cannot identify which juice constituent caused them. Primary reference: Chronic consumption of Annona muricata juice triggers and aggravates cerebral tau phosphorylation in wild-type and MAPT transgenic mice. (2016). https://pubmed.ncbi.nlm.nih.gov/27569447/ DOI: 10.1111/jnc.13835 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    Complete structured claim and evidence

  4. Annonacin inhibited mitochondrial complex-I-linked energy production, producing a concentration-dependent ATP fall, tau redistribution and death in cultured rat striatal neurons.

    Annonacin → Mitochondrial complex-I function and ATP in rat striatal neurons source_derived_draftungraded
    Experimental context and source evidence
    dose
    Annonacin concentration series
    duration
    48 hours
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    evidence_scope
    literature_reviewed; model-specific source-derived curation
    experimental_model
    Primary rat striatal neurons
    limitations
    Purified-cell exposure establishes a hazard mechanism, not the dose delivered to human neurons by a particular graviola food.
    nutrient_topic
    Graviola (Annona muricata) chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Graviola / Annona muricata
    organism
    Primary rat striatal neurons
    plain_language
    Annonacin inhibited mitochondrial complex-I-linked energy production, producing a concentration-dependent ATP fall, tau redistribution and death in cultured rat striatal neurons.
    primary_references
    Annonacin, a natural mitochondrial complex I inhibitor, causes tau pathology in cultured neurons. (2007). https://pubmed.ncbi.nlm.nih.gov/17634376/ DOI: 10.1523/JNEUROSCI.1644-07.2007
    route
    In vitro
    tissue
    ATP, mitochondrial transport, tau localization and cell death

    Graviola (Annona muricata): mechanism of action and interactions (2026-09-20) · lines 44–53

    Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Primary rat striatal neurons · source_derived_draft · unverified_draft

    ## graviola-complex1-atp Annonacin inhibited mitochondrial complex-I-linked energy production, producing a concentration-dependent ATP fall, tau redistribution and death in cultured rat striatal neurons. Model/species: Primary rat striatal neurons Tissue/system: ATP, mitochondrial transport, tau localization and cell death Exposure: Annonacin concentration series Route: In vitro Duration: 48 hours Limits: Purified-cell exposure establishes a hazard mechanism, not the dose delivered to human neurons by a particular graviola food. Primary reference: Annonacin, a natural mitochondrial complex I inhibitor, causes tau pathology in cultured neurons. (2007). https://pubmed.ncbi.nlm.nih.gov/17634376/ DOI: 10.1523/JNEUROSCI.1644-07.2007 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    Complete structured claim and evidence

  5. Forced yeast NDI1 expression or stimulation of anaerobic glycolysis prevented annonacin-associated tau redistribution and neuronal death, whereas antioxidants did not.

    Forced expression of yeast NDI1 NADH dehydrogenase → Annonacin-associated neuronal tau redistribution and death source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    dose
    Annonacin with NDI1 expression, glycolysis stimulation or antioxidants
    duration
    48 hours
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    evidence_scope
    literature_reviewed; model-specific source-derived curation
    experimental_model
    Primary rat striatal neurons
    limitations
    NDI1 is an experimental bypass, and lack of antioxidant rescue does not exclude every redox contribution in vivo.
    nutrient_topic
    Graviola (Annona muricata) chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Graviola / Annona muricata
    organism
    Primary rat striatal neurons
    plain_language
    Forced yeast NDI1 expression or stimulation of anaerobic glycolysis prevented annonacin-associated tau redistribution and neuronal death, whereas antioxidants did not.
    primary_references
    Annonacin, a natural mitochondrial complex I inhibitor, causes tau pathology in cultured neurons. (2007). https://pubmed.ncbi.nlm.nih.gov/17634376/ DOI: 10.1523/JNEUROSCI.1644-07.2007
    route
    In vitro perturbation
    tissue
    Energy-pathway rescue and antioxidant controls
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Graviola (Annona muricata): mechanism of action and interactions (2026-09-20) · lines 55–64

    Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Primary rat striatal neurons · source_derived_draft · unverified_draft

    ## graviola-ndi1-rescue Forced yeast NDI1 expression or stimulation of anaerobic glycolysis prevented annonacin-associated tau redistribution and neuronal death, whereas antioxidants did not. Model/species: Primary rat striatal neurons Tissue/system: Energy-pathway rescue and antioxidant controls Exposure: Annonacin with NDI1 expression, glycolysis stimulation or antioxidants Route: In vitro perturbation Duration: 48 hours Limits: NDI1 is an experimental bypass, and lack of antioxidant rescue does not exclude every redox contribution in vivo. Primary reference: Annonacin, a natural mitochondrial complex I inhibitor, causes tau pathology in cultured neurons. (2007). https://pubmed.ncbi.nlm.nih.gov/17634376/ DOI: 10.1523/JNEUROSCI.1644-07.2007 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    Complete structured claim and evidence

  6. Annonacin exposure produced greater tau accumulation, phosphorylation and redistribution in R406W-MAPT transgenic mice than in mice with endogenous mouse tau.

    Annonacin → Human MAPT R406W tau variant source_derived_draftungraded
    Experimental context and source evidence
    dose
    Experimental annonacin exposure
    duration
    Study interval specified in the primary article
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    evidence_scope
    literature_reviewed; model-specific source-derived curation
    experimental_model
    R406W-MAPT transgenic and non-transgenic mice
    limitations
    Gene-environment interaction in a transgenic model does not establish penetrance or dose-response in humans.
    nutrient_topic
    Graviola (Annona muricata) chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Graviola / Annona muricata
    organism
    R406W-MAPT transgenic and non-transgenic mice
    plain_language
    Annonacin exposure produced greater tau accumulation, phosphorylation and redistribution in R406W-MAPT transgenic mice than in mice with endogenous mouse tau.
    primary_references
    Annonacin, a natural lipophilic mitochondrial complex I inhibitor, increases phosphorylation of tau in the brain of FTDP-17 transgenic mice. (2014). https://pubmed.ncbi.nlm.nih.gov/24389273/ DOI: 10.1016/j.expneurol.2013.12.017
    route
    In vivo mouse exposure
    tissue
    Tau abundance, phosphorylation, localization and proteasomal activity

    Graviola (Annona muricata): mechanism of action and interactions (2026-09-20) · lines 66–75

    Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · R406W-MAPT transgenic and non-transgenic mice · source_derived_draft · unverified_draft

    ## graviola-r406w-synergy Annonacin exposure produced greater tau accumulation, phosphorylation and redistribution in R406W-MAPT transgenic mice than in mice with endogenous mouse tau. Model/species: R406W-MAPT transgenic and non-transgenic mice Tissue/system: Tau abundance, phosphorylation, localization and proteasomal activity Exposure: Experimental annonacin exposure Route: In vivo mouse exposure Duration: Study interval specified in the primary article Limits: Gene-environment interaction in a transgenic model does not establish penetrance or dose-response in humans. Primary reference: Annonacin, a natural lipophilic mitochondrial complex I inhibitor, increases phosphorylation of tau in the brain of FTDP-17 transgenic mice. (2014). https://pubmed.ncbi.nlm.nih.gov/24389273/ DOI: 10.1016/j.expneurol.2013.12.017 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    Complete structured claim and evidence

  7. In a Guadeloupe case-control study, regular Annonaceae fruit and herbal-tea use was reported much more often by PSP or atypical-parkinsonism cases than by Parkinson-disease cases or controls.

    Annonaceae fruit and herbal-tea exposure → Atypical parkinsonism and progressive supranuclear palsy in Guadeloupe source_derived_draftungraded
    Experimental context and source evidence
    dose
    Chronic self-reported Annona muricata/Annona squamosa fruit or tea
    duration
    Retrospective exposure history
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    evidence_scope
    literature_reviewed; model-specific source-derived curation
    experimental_model
    Eighty-seven consecutive Guadeloupe patients with parkinsonism plus frequency-matched controls
    limitations
    Association, recall, combined plant species and unmeasured co-exposures prevent causal attribution to graviola or annonacin.
    nutrient_topic
    Graviola (Annona muricata) chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Graviola / Annona muricata
    organism
    Eighty-seven consecutive Guadeloupe patients with parkinsonism plus frequency-matched controls
    plain_language
    In a Guadeloupe case-control study, regular Annonaceae fruit and herbal-tea use was reported much more often by PSP or atypical-parkinsonism cases than by Parkinson-disease cases or controls.
    primary_references
    Possible relation of atypical parkinsonism in the French West Indies with consumption of tropical plants: a case-control study. Caribbean Parkinsonism Study Group. (1999). https://pubmed.ncbi.nlm.nih.gov/10440304/ DOI: 10.1016/s0140-6736(98)10166-6
    route
    Observational dietary exposure
    tissue
    Clinical classification and recalled plant consumption

    Graviola (Annona muricata): mechanism of action and interactions (2026-09-20) · lines 77–86

    Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Eighty-seven consecutive Guadeloupe patients with parkinsonism plus frequency-matched controls · source_derived_draft · unverified_draft

    ## graviola-human-case-control In a Guadeloupe case-control study, regular Annonaceae fruit and herbal-tea use was reported much more often by PSP or atypical-parkinsonism cases than by Parkinson-disease cases or controls. Model/species: Eighty-seven consecutive Guadeloupe patients with parkinsonism plus frequency-matched controls Tissue/system: Clinical classification and recalled plant consumption Exposure: Chronic self-reported Annona muricata/Annona squamosa fruit or tea Route: Observational dietary exposure Duration: Retrospective exposure history Limits: Association, recall, combined plant species and unmeasured co-exposures prevent causal attribution to graviola or annonacin. Primary reference: Possible relation of atypical parkinsonism in the French West Indies with consumption of tropical plants: a case-control study. Caribbean Parkinsonism Study Group. (1999). https://pubmed.ncbi.nlm.nih.gov/10440304/ DOI: 10.1016/s0140-6736(98)10166-6 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    Complete structured claim and evidence

  8. A 2026 adjusted comparison found worse motor and cognitive scores in Caribbean Parkinson-disease patients, 96% of whom reported Annonaceae exposure, than in mainland-France patients.

    Annonaceae fruit and herbal-tea exposure → Motor and cognitive severity in Caribbean Parkinson disease source_derived_draftungraded
    Experimental context and source evidence
    dose
    Historical Annonaceae-fruit exposure
    duration
    Cross-sectional severity comparison
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    evidence_scope
    literature_reviewed; model-specific source-derived curation
    experimental_model
    Caribbean PD group (74) and mainland-France PD group (104)
    limitations
    Exposure was nearly inseparable from population and geography; the study cannot isolate dose, plant species, or causality.
    nutrient_topic
    Graviola (Annona muricata) chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Graviola / Annona muricata
    organism
    Caribbean PD group (74) and mainland-France PD group (104)
    plain_language
    A 2026 adjusted comparison found worse motor and cognitive scores in Caribbean Parkinson-disease patients, 96% of whom reported Annonaceae exposure, than in mainland-France patients.
    primary_references
    The Clinical Effect of Annonaceae Fruit Consumption on Caribbean Parkinson's Disease Severity. (2026). https://pubmed.ncbi.nlm.nih.gov/42192274/ DOI: 10.1155/bn/8897550
    route
    Observational
    tissue
    UPDRS-III and Mattis Dementia Rating Scale

    Graviola (Annona muricata): mechanism of action and interactions (2026-09-20) · lines 88–97

    Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Caribbean PD group (74) and mainland-France PD group (104) · source_derived_draft · unverified_draft

    ## graviola-human-severity A 2026 adjusted comparison found worse motor and cognitive scores in Caribbean Parkinson-disease patients, 96% of whom reported Annonaceae exposure, than in mainland-France patients. Model/species: Caribbean PD group (74) and mainland-France PD group (104) Tissue/system: UPDRS-III and Mattis Dementia Rating Scale Exposure: Historical Annonaceae-fruit exposure Route: Observational Duration: Cross-sectional severity comparison Limits: Exposure was nearly inseparable from population and geography; the study cannot isolate dose, plant species, or causality. Primary reference: The Clinical Effect of Annonaceae Fruit Consumption on Caribbean Parkinson's Disease Severity. (2026). https://pubmed.ncbi.nlm.nih.gov/42192274/ DOI: 10.1155/bn/8897550 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    Complete structured claim and evidence

  9. Purified annonacin activated p21, increased Bax and caspase-3, and produced G1 arrest and cell death in cultured T24 bladder-cancer cells.

    Annonacin → G1 arrest and apoptosis in T24 bladder-cancer cells source_derived_draftungraded
    Experimental context and source evidence
    dose
    Purified annonacin concentration-response
    duration
    Up to 48 hours
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    evidence_scope
    literature_reviewed; model-specific source-derived curation
    experimental_model
    Human T24 bladder-cancer cells and other cancer lines
    limitations
    Cancer-cell cytotoxicity does not establish tumor selectivity, human efficacy, or a safe graviola product.
    nutrient_topic
    Graviola (Annona muricata) chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Graviola / Annona muricata
    organism
    Human T24 bladder-cancer cells and other cancer lines
    plain_language
    Purified annonacin activated p21, increased Bax and caspase-3, and produced G1 arrest and cell death in cultured T24 bladder-cancer cells.
    primary_references
    Annonacin, a mono-tetrahydrofuran acetogenin, arrests cancer cells at the G1 phase and causes cytotoxicity in a Bax- and caspase-3-related pathway. (2003). https://pubmed.ncbi.nlm.nih.gov/12697268/ DOI: 10.1016/s0024-3205(03)00190-5
    route
    In vitro
    tissue
    Cell cycle and apoptosis markers

    Graviola (Annona muricata): mechanism of action and interactions (2026-09-20) · lines 99–108

    Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Human T24 bladder-cancer cells and other cancer lines · source_derived_draft · unverified_draft

    ## graviola-annonacin-cell-cycle Purified annonacin activated p21, increased Bax and caspase-3, and produced G1 arrest and cell death in cultured T24 bladder-cancer cells. Model/species: Human T24 bladder-cancer cells and other cancer lines Tissue/system: Cell cycle and apoptosis markers Exposure: Purified annonacin concentration-response Route: In vitro Duration: Up to 48 hours Limits: Cancer-cell cytotoxicity does not establish tumor selectivity, human efficacy, or a safe graviola product. Primary reference: Annonacin, a mono-tetrahydrofuran acetogenin, arrests cancer cells at the G1 phase and causes cytotoxicity in a Bax- and caspase-3-related pathway. (2003). https://pubmed.ncbi.nlm.nih.gov/12697268/ DOI: 10.1016/s0024-3205(03)00190-5 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    Complete structured claim and evidence

  10. Annonacin and 4-hydroxytamoxifen additively reduced MCF-7 survival and estrogen-receptor transcriptional activity; annonacin also reduced MCF-7 xenograft growth in nude mice.

    Annonacin → 4-Hydroxytamoxifen inhibition of MCF-7 cell survival source_derived_draftungraded
    Experimental context and source evidence
    dose
    Annonacin 0.1-1 micromolar with 4-hydroxytamoxifen 1 micromolar; mouse dosing in primary article
    duration
    48 hours in cells; 7-22 days in mice
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    evidence_scope
    literature_reviewed; model-specific source-derived curation
    experimental_model
    Human MCF-7 cells and nude-mouse xenografts
    limitations
    Additivity in preclinical models is not evidence to combine graviola with tamoxifen; annonacin toxicity and pharmacokinetics remain limiting.
    nutrient_topic
    Graviola (Annona muricata) chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Graviola / Annona muricata
    organism
    Human MCF-7 cells and nude-mouse xenografts
    plain_language
    Annonacin and 4-hydroxytamoxifen additively reduced MCF-7 survival and estrogen-receptor transcriptional activity; annonacin also reduced MCF-7 xenograft growth in nude mice.
    primary_references
    Annonacin induces cell cycle-dependent growth arrest and apoptosis in estrogen receptor-α-related pathways in MCF-7 cells. (2011). https://pubmed.ncbi.nlm.nih.gov/21840388/ DOI: 10.1016/j.jep.2011.07.056
    route
    In vitro and in vivo
    tissue
    Cell survival, ER-alpha signaling and xenograft size

    Graviola (Annona muricata): mechanism of action and interactions (2026-09-20) · lines 110–119

    Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Human MCF-7 cells and nude-mouse xenografts · source_derived_draft · unverified_draft

    ## graviola-tamoxifen-additivity Annonacin and 4-hydroxytamoxifen additively reduced MCF-7 survival and estrogen-receptor transcriptional activity; annonacin also reduced MCF-7 xenograft growth in nude mice. Model/species: Human MCF-7 cells and nude-mouse xenografts Tissue/system: Cell survival, ER-alpha signaling and xenograft size Exposure: Annonacin 0.1-1 micromolar with 4-hydroxytamoxifen 1 micromolar; mouse dosing in primary article Route: In vitro and in vivo Duration: 48 hours in cells; 7-22 days in mice Limits: Additivity in preclinical models is not evidence to combine graviola with tamoxifen; annonacin toxicity and pharmacokinetics remain limiting. Primary reference: Annonacin induces cell cycle-dependent growth arrest and apoptosis in estrogen receptor-α-related pathways in MCF-7 cells. (2011). https://pubmed.ncbi.nlm.nih.gov/21840388/ DOI: 10.1016/j.jep.2011.07.056 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    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.

Bypassing complex I rescues the cultured-neuron response to annonacin

Condition: machinery_impairment · Yeast NDI1 is expressed or anaerobic glycolysis is stimulated.

Normal role: Annonacin-driven complex-I energy failure lowers ATP and redistributes tau.

Recorded consequence: Tau redistribution and neuronal death are prevented.

Scope: In-vitro mechanistic rescue.

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.

  • Graviola (Annona muricata): mechanism of action and interactions (2026-09-20)Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. 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.

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