Component

Annonacin

Annonaceous acetogenin and mitochondrial complex-I inhibitor; purified-compound findings do not automatically apply to every Annona muricata preparation.

6 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What it acts on

  1. 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

  2. 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

  3. 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

  4. 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

What acts on it

  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

Where it participates (unsigned role)

  1. 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

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

    Evidence, AI assistance and curation standards