Black Walnut / Juglone
Naphthoquinone juglone from black walnut induces ROS/apoptosis, inhibits topoisomerase-II/Pin1 to block proliferation/metastasis; preclinical anticancer potential with hepatotoxicity concerns.
Forms: Black walnut hull powder or capsules (500–1000 mg)
Simple Summary
Juglone overwhelms tumor cells with ROS, poisons DNA copying/repair, and downshifts invasion programs (EMT/MMPs). It’s potent in dishes and animals, but human trials are lacking and liver toxicity is a concern—so it’s exploratory, not clinic-ready.
Evidence at a glance
Low — Strong lab/animal data; no human studies, toxicity barriers.
How it may work
Juglone, a naphthoquinone from black walnut (Juglans nigra), generates reactive oxygen species (ROS) via redox cycling, inducing oxidative stress and apoptosis in cancer cells. It inhibits topoisomerase-II, disrupting DNA replication and repair, and targets Pin1, a prolyl isomerase, to block cancer cell proliferation and metastasis. It also modulates p53 and STAT3 pathways, enhancing cell cycle arrest and reducing tumor invasion.
Targets & pathways
Curated mechanistic targets reported for this agent — how it may act on cells, not proof of a clinical effect.
- ROS Production↑Via redox cycling inducing oxidative stress
- Apoptosis↑
- Topoisomerase-II↓Disrupts DNA replication and repair
- Pin1↓Blocks proliferation and metastasis
- Cell Cycle Arrest↑Modulates p53 and STAT3 pathways
- Tumor Invasion / EMT / MMP↓
Often studied / combined with
Combinations reported in the literature, not a protocol or a recommendation.
- Curcumin: NF-κB/ROS co-targeting.
- Berberine: ROS/STAT3 enhancement.
- Resveratrol: DNA damage synergy.
- Doxorubicin: Enhanced cytotoxicity.
- Cisplatin: Overcomes resistance.
- Etoposide: Topoisomerase co-inhibition.
Overlapping mechanisms
- ROS ↑: Avoid with other strong oxidants to prevent excessive toxicity.
Safety & interactions
Severity and how well-established each signal is are shown separately. Verify everything with your oncologist or pharmacist — absence here does not mean safe.
- Hepatotoxic drugs (e.g., acetaminophen)AvoidMajorTheoreticalAdditive liver risk.
- AnticoagulantsMonitorModerateTheoreticalPotential bleeding risk.
- Doxorubicin / Cisplatin / EtoposideConsiderBeneficialTheoreticalPreclinical synergies for enhanced cytotoxicity.
Timing
- With meals: To reduce GI upset.
- Divided doses: For better tolerance.
References
- PMID 19555768 (melanoma, ROS-mediated cytotoxicity)
- PMID 27155528 (anti-metastatic/anti-angiogenic in pancreatic cancer)
- Mol Med Rep 2020 (ROS, p38–p53; BRAF inhibitor synergy)
- PMID 31184118 (cell-cycle arrest & apoptosis in endometrial cancer)
- TCRT 2012 (in vivo melanoma growth inhibition / radiosensitization)
Research
No published studies for Black Walnut / Juglone yet
New studies appear here once they’ve been reviewed. Browse all studies.
Dose: as studied, not a recommendation
Ranges seen in adjunct / practice use: 500–2000 mg (po) Once or divided daily. No established human anticancer dose; traditional use for hull powder 500–2000 mg/day. Scaled from preclinical juglone data (mouse 1–5 mg/kg → HED 0.08–0.4 mg/kg juglone, ~5–24 mg for 60 kg human); hull juglone content ~1.5 mg/g, equating to ~3–16 g hull, but typical doses lower due to toxicity—use under supervision., No Rx required, but oncology experimental. Juglone content varies; start low, monitor liver function. Consult clinician for adjunct use..
Trials studying Black Walnut / Juglone
No actively-recruiting trials matched right now. Recruiting is not the same as proven. Search ClinicalTrials.gov →