Black Walnut

Clinical Summary

Black walnut hull (from Juglans nigra, native to eastern North America) is primarily used in traditional and integrative medicine as an antiparasitic and antimicrobial agent. The active compound juglone (5-hydroxy-1,4-naphthoquinone) generates reactive oxygen species via redox cycling, disrupting microbial membranes and energy metabolism.

The evidence reality: Despite centuries of ethnobotanical use (Cherokee, Iroquois, European folk medicine) and extensive in vitro/animal research (1000+ PubMed results), there are zero human randomized controlled trials for any indication. Zero meta-analyses. Zero pharmacokinetic studies in humans. All dosing recommendations derive from traditional practice, not clinical data.

Recent research (2024–2026) has substantially expanded the mechanistic picture — juglone now has demonstrated activity in immunomodulation (GvHD model, PMID 38584000), NLRP3 inflammasome inhibition (prostatitis model, PMID 40250034), quorum sensing inhibition against P. aeruginosa biofilms (PMID 38357290), and neuroprotection (spinal cord injury, PMID 41045624). A formal toxicology study (PMID 35899689) established an alarmingly narrow therapeutic window: NOAEL < 5 mg/kg/day in mice with hepatic and renal damage at moderate doses.

Bottom line: Genuine biological activity with no clinical validation. The evidence-to-use ratio is among the worst in herbal medicine. Users are running uncontrolled N=1 experiments. Better-studied alternatives exist for every indication (Berberine, Oregano-Oil, prescription antiparasitics).

Indications & Evidence

Reading this table: Stars = evidence volume/quality. Type = causal relationship (see legend). BH = Bradford Hill criteria met (/9). Safety = FAERS/trial signals for THIS indication. One row = one decision.

Hard rule: Star rating cannot exceed the causal taxonomy ceiling for its Type. E.g., Type=AHE (animal→human) caps at 2/5 regardless of study count.

Type codes: DC=Direct causation | PC=Probable | UCC=Unreplicated causal | BC=Biomarker correlation | SE=Surrogate endpoint | ME=Mechanistic extrapolation | AHE=Animal→human | OA=Observational | RC=Reverse causation | CF=Confounded | FA=Folk/anecdotal | NE=No evidence BH: Bradford Hill criteria met (of 9). 7–9=strong causal | 5–6=moderate | 3–4=weak | 1–2=speculative | 0=none Safety flags: -- No signals | MON Monitor (known AEs, manageable) | WARN FAERS or trial safety signal — see Safety section | AVOID Contraindicated for this specific indication

5/5 Multiple large RCTs + meta-analyses | 4/5 Several human RCTs | 3/5 Some human pilot data | 2/5 Animal data or very limited human | 1/5 No evidence, theoretical only, or debunked

Conditions with NO credible support (1/5): weight loss/detox, blood sugar control, thyroid support, cardiovascular benefits (confusion with J. regia English walnut), cognitive enhancement. These are marketing claims or species confusion — see Deep Dive for details.

Prescribing

Dosing Table

CRITICAL: All dosing is from traditional use — NO clinical trials establish optimal dosing. Evidence quality for dosing: 1/5.

Cycling protocol (recommended): 2–4 weeks on → 2–4 weeks off → reassess. Aligns with parasite life cycles and limits cumulative toxicity risk. Not recommended for continuous use >6 weeks.

Formulation Table

No PK data exists. No human study has measured juglone blood/stool levels after oral ingestion. Likely primary action is local in GI tract. Systemic bioavailability probably <20%.

Safety

Interactions Table

Contraindications

• Pregnancy — potential uterotonic effects; unknown fetal safety
• Lactation — unknown if compounds transfer to breast milk
• Juglandaceae allergy (walnuts, hickory, pecan)
• Severe liver disease (cirrhosis, acute hepatitis) — juglone metabolism requires hepatic function; accumulation risk
• G6PD deficiency — oxidative compound may trigger hemolysis (theoretical)
• Active IBD flare — tannins may irritate inflamed intestinal lining
• Children <2 years — liver too immature for juglone metabolism

Adverse Effects (ranked by frequency)

FAERS Signal Table (from BioMCP)

FAERS context: Zero FAERS reports exist for juglone or oral black walnut hull supplements. The 58 reports under "black walnut" are injection site reactions, urticaria, dyspnoea, and anaphylaxis from allergenic extract immunotherapy — entirely irrelevant to oral supplementation safety. This absence is typical for dietary supplements not in FDA's drug database. It does NOT mean zero adverse events occur — it means nobody has filed MedWatch reports.

Toxicology Data (CRITICAL)

PMID 35899689 (Tata Memorial Centre, India, 2022) — the only formal toxicology study of juglone in mammals:

• Single-dose POD: 118 mg/kg (mouse)
• Sub-acute NOAEL: < 5 mg/kg/day
• BMD-modeled POD for repeated dosing: 1.74 mg/kg/day
• Most sensitive biomarker: AST (BMDL = 0.011 mg/kg/day)
• Findings: Hepatic and renal damage at 15 and 50 mg/kg/day. Dose-dependent mortality in sub-acute study.
• Implication: Extremely narrow therapeutic window. The difference between potentially therapeutic and toxic doses may be small.

Monitoring Table

Stop criteria: ALT/AST >2× ULN, severe GI symptoms unresponsive to dose reduction, signs of hemolysis (dark urine, jaundice), allergic reaction.

Synergies & Stacking

Traditional "Parasite Cleanse" Stack (Clark protocol): Black walnut hull 1000 mg + Wormwood 200–300 mg + Clove 500 mg, all 2–3×/day for 3 weeks. Evidence: 2/5 traditional use; zero clinical trials. Note: This protocol traces to Hulda Clark (see Community section for context on Clark's controversial claims).

Individual Response Modifiers

Sex-Specific Considerations

Key studies were done predominantly in one sex: The coccidiosis study (40186391) and GvHD study (38584000) did not clearly report sex-stratified outcomes. The prostatitis study (40250034) is inherently male-specific. No sex-specific human data exists.

Genetic Modifiers

No known pharmacogenomic modifiers for black walnut/juglone. No publications on genetic polymorphisms affecting response to juglone have been identified.

Theoretical relevance (not validated):

• CYP enzymes: Juglone likely undergoes CYP-mediated metabolism, but which isoforms and whether polymorphisms matter is unknown
• G6PD deficiency: As a pro-oxidant, juglone may pose hemolysis risk in G6PD-deficient individuals — this is a pharmacological concern, not a pharmacogenomic modifier per se

Community & Anecdotal Evidence

Disclaimer: This section captures real-world user reports from online communities. None of this constitutes clinical evidence. N-sizes are approximate. Selection bias, placebo effect, and recall bias are inherent. Presented for completeness, not as medical guidance.

Dominant Sentiment

Mixed-to-cautiously-positive across ~50–80 substantive threads. ~40% positive, ~30% neutral/uncertain, ~30% negative/skeptical.

The Hulda Clark Shadow

60–70% of online discussion about black walnut traces to Hulda Clark (1928–2009), who promoted a "parasite cleanse" protocol in The Cure for All Cancers (1993) and The Cure for All Diseases (1995). Clark claimed parasites caused virtually all disease including cancer and AIDS. The FTC charged the Dr. Clark Research Association with unsubstantiated health claims. Her claims were not supported by evidence.

Independent use is growing: Post-2020, ~20–30% of discussion comes from non-Clark contexts — primarily herbal SIBO protocols or standalone antifungal use in r/Biohackers, r/SIBO, and integrative medicine forums.

What Users Report

Community Dosing vs Clinical

Popular Stacks (Community)

Red Flags & Skepticism Notes

• Single-influencer origin: HIGH risk — Clark legacy dominates 60–70% of discussion
• Unfalsifiable framing: HIGH risk — "Die-off means it's working" / "No parasites doesn't mean it didn't work" makes failure impossible to detect
• TikTok viral trend (2023–2024): "Parasite cleanse" content with dramatic testimonials, product affiliate links, "everyone has parasites" premise contradicts developed-nation epidemiology
• MLM involvement: Minor — no major MLM companies identified, but Clark Store active marketing
• Astroturfing signals: Moderate — Dr. Clark Store marketing; TikTok affiliate patterns
• Thyroid/iodine claim debunked: Multiple herbalists claim hulls are "highest natural iodine" — no scientific sources confirm meaningful iodine content. Brown stain is juglone/tannins, not iodine.
• East Asian absence is notable: Japan, South Korea, Taiwan supplement communities (typically early adopters of genuine signals like NMN, astaxanthin, nattokinase) have not adopted black walnut hull. Suggests Western interest is culturally/ideologically driven rather than evidence-driven.

Folk vs Clinical Reality Check

Community experience aligns with clinical data in one area: GI activity. Users consistently report GI effects (bloating relief, changed bowel habits, nausea, cramping), which is pharmacologically plausible given juglone's antimicrobial and tannin-astringent properties acting locally in the GI tract.

Community experience diverges from clinical data in claiming: (1) visible parasite expulsion (difficult to verify, high placebo/expectation bias), (2) broad health improvements beyond GI (energy, mood, immunity — no mechanism supports this), and (3) that "die-off" symptoms confirm efficacy (could simply be side effects reframed by confirmation bias). The most likely explanation for divergence: powerful expectation effects from the Clark narrative framework, combined with genuine GI-active properties of tannins being misattributed to "parasite killing."

Deep Dive: Mechanisms & Research

Core Mechanism: Juglone Redox Cycling

Juglone (5-hydroxy-1,4-naphthoquinone, MW 174.15) is the primary bioactive. The naphthoquinone structure accepts and donates electrons repeatedly, generating superoxide radicals and hydrogen peroxide in target cells. This overwhelms antioxidant defenses (glutathione, catalase), causing membrane damage, protein carbonylation, and DNA strand breaks.

Key property: Dose-dependent polarity — at low doses, juglone may induce hormetic (protective) stress responses in human cells; at high doses, it causes oxidative damage. This explains the paradox of protective effects in some studies (PMID 37659348: liver/kidney protection from electric field damage) alongside cytotoxicity in others.

Recent Mechanistic Advances (2024–2026)

Pin1 Inhibition — Juglone is an established inhibitor of peptidyl-prolyl isomerase Pin1, which plays roles in:

• T-cell activation (PMID 41427722) — suppresses PKCθ activity
• Neutrophil oxidative burst (PMID 38851160) — reduces NADPH oxidase priming
• Respiratory inflammation (PMID 40752765) — protects against LPS-induced lung injury in rats at 3 mg/kg IP
• Wound healing signaling (PMID 38795154)

NLRP3 Inflammasome Suppression — Juglone directly binds NLRP3, caspase-1, and GSDMD, alleviating prostatic inflammation in murine EAP model (PMID 40250034).

Quorum Sensing Inhibition — Inhibits PqsR-mediated quorum sensing in P. aeruginosa, reducing pyocyanin and biofilm formation. Synergistic with colistin against CF clinical isolates (PMID 38357290). This is the strongest clinical-relevance antimicrobial finding.

Ferroptosis Induction — Novel anticancer mechanism via FOSL1-HMOX1 axis in hepatocellular carcinoma (PMID 39923427).

Blood-Brain Barrier Permeability — PAMPA study (PMID 39000038, Semmelweis University) demonstrated juglone crosses both GI and BBB membranes via passive diffusion. First evidence of potential CNS access.

Neuroprotection — Promotes spinal cord injury recovery by suppressing pyroptosis/necroptosis via FOS/USP53/ubiquitination pathway (PMID 41045624).

Hair Keratin Interaction — Forms Michael adducts with cysteine residues in damaged hair keratin; SEM confirms surface morphology restoration (PMID 38257235). Potential cosmetic/restorative application.

Skin/Dermatological — Irreversibly inhibits PTP1B phosphatase (75% inhibition) by modifying catalytic Cys215 in human keratinocytes; enhances EGFR phosphorylation 3-fold (PMID 40618430). Relevant to wound healing and skin repair signaling.

Anticancer Research: Volume Without Translation

64 papers (2023–2026) on juglone + cancer — ALL in vitro or xenograft models. Cancer types studied: melanoma, colon, gastric, hepatocellular, breast, osteosarcoma, AML, bladder, oral, lung, ovarian, glioma. Mechanisms: ferroptosis, pyroptosis, apoptosis, STAT3 inhibition, MMP-1 targeting, RIPK pathway.

RETRACTION: PMID 41402162 — the 2016 juglone + Q7 + ascorbate in vivo anticancer study was retracted in 2026, removing one of the few in vivo anticancer data points.

STAT3 inhibitor development (PMID 40637021, J Med Chem, 2025): Juglone derivatives achieved IC50 = 190 nM as STAT3 inhibitors with ~90% tumor growth inhibition at 10 mg/kg in breast cancer xenograft — published in a top medicinal chemistry journal. This represents pharmaceutical-grade derivative development, not a supplement application.

Honest assessment: The anticancer literature demonstrates that juglone has real cytotoxic mechanisms, but this is pharmacological drug development territory, not supplement territory. Many compounds kill cancer cells in vitro. The "NOT a cancer treatment" stance remains fully warranted.

Antiparasitic Evidence: Still Mostly Traditional

Modern data:

• PMID 40186391 (2025): Juglone reduces oocyst shedding, restores intestinal structure, and modulates immune response in murine coccidiosis (E. papillata). This is the best modern antiparasitic evidence — but coccidiosis (protozoan) ≠ helminthiasis (worms), which is the traditional use.
• PMID 36461604 (2022): 8 mg/kg juglone reduced male schistosome worm count by 63.1% and hepatic eggs by 65.7% in mice. Anti-fibrotic and immunomodulatory. Interesting but murine/schistosomiasis.
• PMID 41831868 (2026): Juglone derivatives as nematicides — but agricultural pest nematicides, not human antiparasitics.

Gap: No study tests juglone/black walnut against the specific parasites users are targeting: pinworms, roundworms, hookworms in humans.

Antimicrobial Evidence: Growing and Mechanistically Rich

Assessment: The antimicrobial data is the most clinically promising area — especially the quorum sensing and antibiotic potentiation findings. However, ALL data is in vitro or animal wound models. No oral antimicrobial human trial exists.

Clinical Trials (from BioMCP / ClinicalTrials.gov)

Note: NCT04849949 measured postprandial metabolic responses to eating whole black walnuts as food — NOT therapeutic evaluation of hull extract or juglone. This is the only black walnut-specific registered trial. Zero juglone therapeutic trials exist on ClinicalTrials.gov or East Asian registries (JPRN, CRiS, ChiCTR).

Regulatory Status (from BioMCP)

• FDA: No drug approval. Black walnut hull sold as dietary supplement under DSHEA. No GRAS designation for juglone.
• EMA: No monograph, no regulatory status
• Health Canada: Licensed as Natural Health Product in some formulations
• WHO: No monograph for J. nigra
• American Herbal Pharmacopoeia: No monograph
• Regulatory context: No pharmaceutical company has pursued juglone for drug approval. Likely reasons: non-patentable natural compound, narrow therapeutic window (PMID 35899689), and sufficient better-characterized alternatives exist for all target indications. Not a conspiracy — a market economics reality.

Research Geography

Chinese institutions dominate recent juglone research (2024–2026): Fudan, China Pharmaceutical, Shandong, Anhui Medical, Guizhou Medical, Dalian Medical, Xinjiang Agricultural, Lanzhou Universities. Most work is anticancer mechanisms or antimicrobial characterization.

India: Tata Memorial Centre produced the only formal toxicology study (PMID 35899689) and the GvHD immunomodulation study (PMID 38584000) — the highest-quality translational work.

Europe: France (MRSA adjuvant, PMID 38996547), Italy (hair keratin, PMID 38257235; juglone derivatives, PMID 41463363), Hungary (polyphenol characterization, PMID 39000038).

Japan, Taiwan, South Korea: No significant juglone-specific publications found in 2024–2026.

Ataraxia Verdict (as of 2026-04-14)

Evidence Classification (Mode 5: Evidence Classifier)

Synthesized view in Indications & Evidence table above (Type + BH + Safety columns). Detailed rationale below.

Hype Check (Mode 1: Fallacy Radar)

• Appeal to tradition (HIGH): "Used for centuries" is the primary evidence anchor. Existence of traditional practice ≠ proof of efficacy. Countless traditional remedies proved ineffective or harmful on clinical testing.
• In vitro → human generalization (HIGH): 1000+ PubMed results create an illusion of strong evidence. Volume of preclinical publications ≠ clinical validation. Bleach kills cancer cells in vitro too.
• Appeal to nature (HIGH): "Natural antiparasitic" framing implicitly suggests safety. Juglone is natural AND toxic (allelopathic compound that kills plants; narrow therapeutic window confirmed by PMID 35899689).
• Argument from popularity (MEDIUM): The Clark protocol is enormously popular online. Popularity ≠ evidence. Clark's cancer/AIDS cure claims were entirely unsupported.
• Die-off unfalsifiability (HIGH): "Herxheimer reaction" framing makes adverse effects CONFIRMATORY rather than warning signs, preventing users from correctly interpreting side effects.

Evidence Gaps

1. Zero human pharmacokinetic data — biggest gap; all dosing is guesswork
2. Zero human RCTs for any indication — efficacy cannot be quantified
3. No human safety study — hepatotoxicity threshold in humans unknown
4. No standardization method — juglone content varies wildly between products
5. No microbiome impact study — broad antimicrobial effects on beneficial bacteria unknown
6. No study tests against the specific parasites users target (pinworms, roundworms in humans)
7. Hair/skin applications untranslated — promising in vitro work (38257235, 40618430) with zero follow-up

Bias Flags (Mode 4: First Principles)

• The core assumption is unexamined: "Traditional antiparasitic use implies current efficacy" — remove this and there's almost nothing left for the supplement use case
• "Oral supplementation achieves therapeutic GI concentrations" — assumed by every user; never tested
• Publication bias toward positive in vitro results — negative results (juglone didn't kill organism X, or killed host cells too) are underreported
• Chinese research dominance in anticancer: 10+ institutions publishing juglone anticancer papers in 2024–2026, mostly network pharmacology + xenograft. This volume reflects Chinese academic incentive structures more than translational promise

Manipulation Flags (Mode 2: Manipulation Shield)

• Industry marketing: Hulda Clark ecosystem (Dr. Clark Store, parasite cleanse kits $40–80) is the dominant commercial driver. TikTok affiliate marketing (2023–2024 viral trend) amplified demand.
• Influencer economics: Clark's books created a self-sustaining protocol ecosystem. No single current influencer dominates, but the "parasite anxiety" narrative generates engagement across social media.
• Counter-narrative manipulation: No significant pharma FUD detected — generic antiparasitics are cheap; no competitor has incentive to discredit black walnut. Safety concerns come from pharmacological reasoning, not commercial actors.
• Cui bono summary: Supplement companies and Clark-adjacent vendors profit if you take it. Nobody profits specifically if you don't (no competing product at this price point). Emergency physicians reporting adverse events have zero commercial motive — their warnings carry higher weight.
• Red team highlight: The "Herxheimer reaction" reframe is the most concerning manipulation pattern — it converts negative effects (nausea, headache, fatigue) into perceived evidence of efficacy, preventing rational discontinuation decisions.

Decision Support (Mode 3: Clarity Compass)

• Health utility score: 2/10 — extremely narrow indication profile (only confirmed parasitic/fungal infection), zero human clinical trials, and prescription antiparasitics outperform it for any confirmed infection; no general-population utility.
• Opportunity cost: Complexity cost (cycling protocol), iron absorption interference, potential microbiome disruption, liver monitoring requirement — for a compound with zero proven human efficacy.
• Verdict: CONDITIONAL — Use ONLY if:
  1. Stool testing confirms parasitic infection AND
  2. Prescription antiparasitics (albendazole, mebendazole — >90% cure rates) are unavailable or contraindicated AND
  3. Duration limited to 2–4 weeks with LFT monitoring
• For all other scenarios: SKIP. Better-evidenced alternatives exist for every proposed indication.

Bottom Line

Black walnut hull has genuine biological activity — juglone's antimicrobial, anti-inflammatory, and immunomodulatory mechanisms are real and well-characterized in preclinical models. The compound has the worst evidence-to-use ratio in herbal medicine: 1000+ publications, zero human trials. The community use case is dominated by a pseudoscientific legacy (Hulda Clark), amplified by social media virality, and sustained by an unfalsifiable "die-off" narrative that prevents users from recognizing adverse effects.

For the biohacker considering this compound: Your money and liver function tests are better spent on Berberine (multiple RCTs, broad-spectrum antimicrobial, metabolic benefits), Oregano-Oil (some human SIBO data), or prescription antiparasitics (>90% cure rates). If you insist on using black walnut hull: confirm your diagnosis with stool testing, cycle 2–4 weeks max, monitor LFTs, space iron supplements by 4+ hours, and start at half-dose. Do not interpret side effects as "die-off" — they may be telling you to stop.

Practical Notes

Brands (examples, not endorsements): Herb Pharm (tincture; organic; third-party tested), Gaia Herbs (capsules; organic), NOW Foods (budget capsules), Nature's Answer (alcohol-free). Look for: hull (not bark/leaf) specified, dark glass, third-party COA, naphthoquinone content if available. Avoid: clear glass bottles, "miracle cure" claims, no plant part specified, no manufacturer info.

Storage: Dark amber/violet glass, room temperature, airtight. Tinctures 2–3 years; capsules 1–2 years. Fresh hulls degrade in weeks. Signs of degradation: color fading, off odor, clumping.

Taste management (tincture): Mix in 2 oz strong juice (grape/orange), hold breath, drink fast, chase with orange slice or dark chocolate.

Iron scheduling: If taking iron for anemia, schedule iron at bedtime and black walnut in AM/afternoon — 6–8 hour spacing maximizes both.

Herxheimer or side effect? There is no reliable way to distinguish die-off from adverse effects without testing. If symptoms are severe enough to question, reduce dose or stop. Do not use "die-off" as justification to push through significant adverse effects.

When to escalate: If no symptom improvement after full 3-week cycle for parasites, obtain formal stool O&P and consider prescription antiparasitics. Don't repeat multiple cycles without confirmed diagnosis.

DIY tincture: 200g fresh green hulls : 1000 mL vodka/grain alcohol, macerate 4–6 weeks in dark glass, shake daily, strain. Requires proper J. nigra identification.

What We Don't Know

• Whether oral black walnut hull supplements achieve therapeutic juglone concentrations in the human GI tract
• Juglone's pharmacokinetics in humans (absorption, distribution, metabolism, excretion, half-life)
• Optimal dose for any indication in humans
• Safe duration of use in humans (mouse NOAEL alarmingly low)
• Impact on human gut microbiome composition
• Whether it works better than placebo for intestinal parasites in humans
• Whether "Herxheimer" symptoms during use are genuine die-off or adverse effects
• Which human parasites (if any) are susceptible at achievable GI concentrations
• Long-term effects of repeated cycling
• Whether the iodine content claim has any basis
• Whether juglone's BBB permeability (PAMPA-demonstrated) translates to any CNS effects in vivo
• Whether the hair keratin and skin PTP1B findings translate to consumer applications

References

Toxicology & Safety

• PMID 35899689 — Tata Memorial Centre (2022). Acute + sub-acute oral toxicity of juglone in mice. NOAEL < 5 mg/kg/day. Hepatic/renal damage at moderate doses. THE critical safety reference.

Immunomodulation & Inflammation

• PMID 38584000 — Gohil et al. (2026). Juglone alleviates acute GvHD while preserving GvL activity in mice. Br J Pharmacol. First oral dosing framework.
• PMID 40250034 — Xu et al. (2025). Juglone alleviates pelvic pain and prostatic inflammation via NLRP3 inflammasome inhibition in EAP mice. Phytomedicine.
• PMID 40752765 — Kouki et al. (2025). Juglone protects against LPS-induced respiratory inflammation in rats via Pin1 inhibition. Eur J Pharmacol.

Antimicrobial & Anti-biofilm

• PMID 38357290 — Ma et al. (2024). Juglone as quorum sensing inhibitor against P. aeruginosa pqs-mediated virulence and biofilms. Synergistic with colistin vs CF clinical isolates. ACS Pharmacol Transl Sci.
• PMID 41655799 — Phatak et al. (2026). Multi-targeted antimicrobial action of juglone against P. mirabilis biofilm and virulence. Microb Pathog.
• PMID 41520389 — Nimir & Darmani (2026). Juglone antibacterial vs E. faecalis compared with chlorhexidine. Superior virulence inhibition. Arch Oral Biol.
• PMID 38996547 — Majdi et al. (2024). Amino-juglone derivative potentiates cloxacillin 66-fold against MRSA. Bioorg Chem.
• PMID 36835350 — Wan et al. (2023). Juglone antibacterial activity in S. aureus wound model. Int J Mol Sci.
• PMID 41107751 — Broad-spectrum mechanism study: MIC 15.6 µg/mL against E. coli, S. aureus, S. pullorum. BMC Microbiol (2025).
• PMID 37075666 — Majdi et al. (2023). Review: antibacterial properties of juglone, naphthazarin, plumbagin, lawsone and their metal complexes. Biomed Pharmacother.

Antiparasitic

• PMID 40186391 — Kasem et al. (2025). Juglone as therapeutic agent in murine coccidiosis: intestinal recovery and immune modulation. Microsc Res Tech.
• PMID 36461604 — (2022). Juglone reduces schistosome worm burden 63%, hepatic eggs 66% in mice. Int Immunopharmacol.
• PMID 38789822 — Mir et al. (2024). Walnut leaf extract anthelmintic activity against Ascaridia galli in chickens. Vet Res Commun. (Note: J. regia not J. nigra.)

Neuroprotection & CNS

• PMID 41045624 — Chen et al. (2025). Juglone promotes SCI recovery by suppressing pyroptosis and necroptosis via FOS/USP53 pathway. Phytomedicine.
• PMID 39000038 — (2024). UHPLC-HR-MS/MS characterization of J. nigra; PAMPA demonstrates juglone BBB permeability. Int J Mol Sci.
• PMID 38004442 — Santos et al. (2023). Naphthoquinones as a class for Parkinson's disease. Pharmaceuticals.

Skin & Hair

• PMID 40618430 — Arnaud et al. (2025). Juglone irreversibly inhibits PTP1B in human keratinocytes; enhances EGFR phosphorylation 3-fold. Mol Pharmacol.
• PMID 38257235 — Di Foggia et al. (2024). Juglone forms Michael adducts with damaged hair keratin; SEM restoration. Molecules.

Anticancer (representative — all preclinical)

• PMID 39923427 — Wang et al. (2025). Juglone induces ferroptosis in HCC via FOSL1-HMOX1. Phytomedicine.
• PMID 40637021 — (2025). Juglone derivatives as STAT3 inhibitors (IC50 190 nM) for breast cancer. J Med Chem.
• PMID 40885322 — Zhou et al. (2025). Juglone targets MMP-1 to inhibit gastric cancer progression. Biochem Pharmacol.
• PMID 41380825 — Miao et al. (2026). Anti-osteosarcoma via ROS/PI3K/AKT. Eur J Pharmacol.
• PMID 41402162 — RETRACTED (2026). Original 2016 juglone + Q7 + ascorbate in vivo anticancer study.
• PMID 35272138 — Tang et al. (2022). Review: molecular mechanisms of juglone in cancer therapies. Biomed Pharmacother. (Only systematic review.)

Phytochemistry & Biosynthesis

• PMID 30393558 — McCoy et al. (2018). Origin and biosynthesis of juglone in black walnut. Hort Res.
• PMID 24354204 — Paudel et al. (2013). J. regia vs J. nigra leaf essential oil comparison. Nat Prod Commun.

Ethnobotanical & Traditional Use

• PMID 19589387 — Aithal et al. (2009). Juglone cytotoxicity in melanoma cells. Cell Biol Int.
• PMID 16782281 — Kozan et al. (2006). Turkish folk medicine plants evaluated for anthelmintic activity. J Ethnopharmacol.
• PMID 10624876 — Guarrera (1999). Traditional antihelmintic uses of plants in Central Italy. J Ethnopharmacol.
• PMID 17628336 — Lans et al. (2007). Ethnoveterinary use of black walnut for endoparasites. Vet Parasitol.
• Heron & Yarnell (1999). Review of botanical antiparasitics including black walnut. Alt Complement Ther.
• PMID 14130723 — Auyong et al. (1963). Pharmacological aspects of juglone (earliest toxicology). Toxicon.

Clinical Trial

• NCT04849949 — Black Walnuts and Health. University of Georgia. Completed 2018. N=34. Measured postprandial TG, glucose, insulin, antioxidant capacity after eating whole black walnuts (food, not hull supplement).