Macelignan

Macelignan at a Glance

Macelignan is a dibenzylbutane lignan that also appears in databases and in recent pharmacokinetic work under the name anwuligan (and (+)-anwulignan). All three denote the same molecule (CAS 107534-93-0, PubChem CID 10404245), and the great bulk of the published research uses “macelignan.” It is chiefly a constituent of nutmeg — the mace and seed of Myristica fragrans — and is also reported, in much smaller amounts, in Schisandra chinensis ^{7,8Reference 7Paul S et al. · 2013Multiple biological properties of macelignan and its pharmacological implicationsView study →Reference 8Cheng X et al. · 2026Mechanism-based inactivation of CYP2C19 by anwuligan resulting in changes in pharmacokinetic properties of amitriptylineView study →}.

Because “macelignan” dominates the literature, that is where its pharmacology has been documented: a broad preclinical profile spanning anti-cariogenic / antibacterial, antioxidant, anti-inflammatory, hepatoprotective, neuroprotective and PPAR-mediated antidiabetic activity ^{7Reference 7Paul S et al. · 2013Multiple biological properties of macelignan and its pharmacological implicationsView study →}. Almost all of this is cell-culture and rodent work; there are no human clinical trials of the isolated molecule.

The single most practically relevant finding is not a benefit but an interaction: macelignan is a mechanism-based (irreversible) inactivator of the drug-metabolising enzyme CYP2C19, and in animals it measurably raised exposure to the CYP2C19 substrate amitriptyline ^{8Reference 8Cheng X et al. · 2026Mechanism-based inactivation of CYP2C19 by anwuligan resulting in changes in pharmacokinetic properties of amitriptylineView study →}. That makes its enzyme behaviour, rather than any proven therapeutic use, the headline for anyone thinking about nutmeg-derived lignan intake alongside medication.

Macelignan, Anwuligan and (+)-Anwulignan Are One Molecule

The naming is the first thing to get straight, because it changes what evidence applies. “Anwuligan,” ”(+)-anwulignan” and “macelignan” all denote the same dibenzylbutane lignan — identical CAS number (107534-93-0), identical PubChem entry (CID 10404245), molecular formula C20H24O4 ^{7Reference 7Paul S et al. · 2013Multiple biological properties of macelignan and its pharmacological implicationsView study →}. “Macelignan” is the name under which the compound was first characterised as the anti-cariogenic principle of nutmeg mace, and it remains the dominant literature name ^{1,7Reference 1Chung JY et al. · 2006Anticariogenic activity of macelignan isolated from Myristica fragrans (nutmeg) against Streptococcus mutansView study →Reference 7Paul S et al. · 2013Multiple biological properties of macelignan and its pharmacological implicationsView study →}; “anwuligan” appears mostly in more recent pharmacokinetic and interaction work ^{8Reference 8Cheng X et al. · 2026Mechanism-based inactivation of CYP2C19 by anwuligan resulting in changes in pharmacokinetic properties of amitriptylineView study →}.

The practical consequence, and the reason it is filed under macelignan: that is where the evidence is. Searching “anwuligan” returns a handful of recent papers and misses the anti-cariogenic, metabolic and neuroprotective literature entirely. Every application below is drawn from the macelignan literature and cross-checked to the same compound. Anwuligan is the same compound under an older name.

What It's Used For

Macelignan has a wide but shallow evidence base — many reported activities, essentially all preclinical (isolated compound in cells, or in rodents), with no human trials. The evidence is strongest where the isolate was tested directly and quantitatively, weakest where it rests on a single study or a narrative review.

Evidence by IndicationStrength of support · Beta

Support is an experimental score — weighted by study type (human > animal > in vitro) and volume. A beta, not a validated metric. Every row here is preclinical, so scores stay low; read the per-row basis for what kind of study each rests on.

01Anti-cariogenic / antibacterialShaky44%Quantitative in-vitro MIC vs. oral bacteria (isolate) ^{1Reference 1Chung JY et al. · 2006Anticariogenic activity of macelignan isolated from Myristica fragrans (nutmeg) against Streptococcus mutansView study →}

02Antidiabetic / metabolic (PPARα/γ)Shaky40%Oral dosing in diabetic db/db mice (isolate) ^{2Reference 2Han KL et al. · 2008Therapeutic potential of peroxisome proliferators-activated receptor-alpha/gamma dual agonist with alleviation of endoplasmic reticulum stress for the treatment of diabetesView study →}

03Neuroprotective / anti-inflammatoryShaky32%Multiple glial/neuronal cell models incl. Alzheimer’s ^{3,4,5Reference 3Jin DQ et al. · 2005AnimalAnti-oxidant and anti-inflammatory activities of macelignan in murine hippocampal cell line and primary culture of rat microglial cellsView study →Reference 4Zong K et al. · 2020Macelignan inhibits the inflammatory response of microglia and regulates neuronal survivalView study →Reference 5Gu L et al. · 2022Inhibitory effects of macelignan on tau phosphorylation and Aβ aggregation in the cell model of Alzheimer’s diseaseView study →}

04HepatoprotectiveShaky26%Single chemical-injury study + narrative review ^{6,7Reference 6Sohn JH et al. · 2008Protective effects of macelignan on cisplatin-induced hepatotoxicity is associated with JNK activationView study →Reference 7Paul S et al. · 2013Multiple biological properties of macelignan and its pharmacological implicationsView study →}

Mechanisms

The mechanisms cluster around two hubs — PPAR/ER-stress in metabolism and NF-κB-adjacent inflammatory suppression in glia — but the CYP2C19 line is the one with a directly demonstrated in-vivo pharmacokinetic consequence ^{8Reference 8Cheng X et al. · 2026Mechanism-based inactivation of CYP2C19 by anwuligan resulting in changes in pharmacokinetic properties of amitriptylineView study →}.

Pharmacokinetics

Macelignan is a small, lipophilic lignan (C20H24O4, MW 328.4), and its metabolic-tissue and CNS-model effects imply it is absorbed and distributed enough to act in oral rodent studies ^{2Reference 2Han KL et al. · 2008Therapeutic potential of peroxisome proliferators-activated receptor-alpha/gamma dual agonist with alleviation of endoplasmic reticulum stress for the treatment of diabetesView study →}. Its best-characterised pharmacokinetic property is at the enzyme end: anwuligan is a mechanism-based inactivator of CYP2C19 — it is metabolised to a reactive intermediate that irreversibly disables the enzyme — and in animals, pretreatment raised the peak concentration of the CYP2C19 substrate amitriptyline ~1.4-fold and its overall exposure by ~30%, while lowering the active metabolite nortriptyline ^{8Reference 8Cheng X et al. · 2026Mechanism-based inactivation of CYP2C19 by anwuligan resulting in changes in pharmacokinetic properties of amitriptylineView study →}. Beyond this, quantitative human pharmacokinetics — oral bioavailability, half-life, protein binding, its own clearance route — are not established.

Clinical Trials

There are no human clinical trials of isolated macelignan for any indication. The entire evidence base is preclinical (isolated-compound in-vitro and rodent studies) plus one narrative review ^{7Reference 7Paul S et al. · 2013Multiple biological properties of macelignan and its pharmacological implicationsView study →}.

Last checked: July 2026.

Isolate vs. Plant Studies

This molecule’s evidence is unusually isolate-heavy, which cuts both ways. On the plus side, the marquee findings — the anti-cariogenic MIC ^{1Reference 1Chung JY et al. · 2006Anticariogenic activity of macelignan isolated from Myristica fragrans (nutmeg) against Streptococcus mutansView study →}, the db/db metabolic study ^{2Reference 2Han KL et al. · 2008Therapeutic potential of peroxisome proliferators-activated receptor-alpha/gamma dual agonist with alleviation of endoplasmic reticulum stress for the treatment of diabetesView study →}, the glial/neuronal and Alzheimer’s models ^{3,4,5Reference 3Jin DQ et al. · 2005AnimalAnti-oxidant and anti-inflammatory activities of macelignan in murine hippocampal cell line and primary culture of rat microglial cellsView study →Reference 4Zong K et al. · 2020Macelignan inhibits the inflammatory response of microglia and regulates neuronal survivalView study →Reference 5Gu L et al. · 2022Inhibitory effects of macelignan on tau phosphorylation and Aβ aggregation in the cell model of Alzheimer’s diseaseView study →}, the cisplatin-liver study ^{6Reference 6Sohn JH et al. · 2008Protective effects of macelignan on cisplatin-induced hepatotoxicity is associated with JNK activationView study →} and the CYP2C19 work ^{8Reference 8Cheng X et al. · 2026Mechanism-based inactivation of CYP2C19 by anwuligan resulting in changes in pharmacokinetic properties of amitriptylineView study →} — all tested purified macelignan/anwuligan, so the activity is genuinely the molecule’s, not an extract’s. On the minus side, none of it is human, and the isolate was rarely compared against whole nutmeg or Schisandra extract, so how much the compound contributes to either plant’s overall effect is unquantified. Nutmeg’s own dominant pharmacology — and its notorious toxicity — is driven by different constituents (the phenylpropene myristicin and related volatiles), not by this lignan.

Prevalence in Nature

Macelignan is primarily a nutmeg compound. It was isolated and structurally identified from the methanol extract of Myristica fragrans mace (and seed), where it occurs alongside related dibenzyl/neolignans (including nectandrin B, and built on the same C6–C3 units as eugenol); it is the lignan behind nutmeg’s reported anti-cariogenic activity ^{1,7Reference 1Chung JY et al. · 2006Anticariogenic activity of macelignan isolated from Myristica fragrans (nutmeg) against Streptococcus mutansView study →Reference 7Paul S et al. · 2013Multiple biological properties of macelignan and its pharmacological implicationsView study →}. It is also reported as a minor lignan of Schisandra chinensis — the attribution in the CYP2C19 study, which describes the compound as “derived from nutmeg and Schisandra chinensis” ^{8Reference 8Cheng X et al. · 2026Mechanism-based inactivation of CYP2C19 by anwuligan resulting in changes in pharmacokinetic properties of amitriptylineView study →} — but the Schisandra occurrence is far less documented than the nutmeg one, and Schisandra’s characteristic lignans (schisandrin, schisandrol B, schisantherin A) are structurally distinct dibenzocyclooctadiene types rather than this open-chain dibenzylbutane.

No quantified concentration figures (percent dry weight, mace vs. seed vs. Schisandra fruit) are established for macelignan in either source — a gap logged for a later pass. Reported occurrence should be read as “present in nutmeg, minor in Schisandra,” not as a measured abundance.

Discovery & Synthesis

Macelignan entered the literature under that name, as the constituent isolated from nutmeg (Myristica fragrans) mace by repeated silica-gel chromatography and characterised by 1D/2D-NMR and EI-MS as the anti-cariogenic principle of the spice, with the landmark Phytomedicine report in 2006 ^{1Reference 1Chung JY et al. · 2006Anticariogenic activity of macelignan isolated from Myristica fragrans (nutmeg) against Streptococcus mutansView study →}. The names “anwuligan” and ”(+)-anwulignan” denote the same dibenzylbutane lignan (CAS 107534-93-0) and are used interchangeably with “macelignan” in the chemical and pharmacological literature ^{7Reference 7Paul S et al. · 2013Multiple biological properties of macelignan and its pharmacological implicationsView study →}. The bulk of the pharmacology (anti-diabetic PPAR work, neuroprotection, hepatoprotection) accumulated over 2005–2013 under the macelignan name ^{2,3,6,7Reference 2Han KL et al. · 2008Therapeutic potential of peroxisome proliferators-activated receptor-alpha/gamma dual agonist with alleviation of endoplasmic reticulum stress for the treatment of diabetesView study →Reference 3Jin DQ et al. · 2005AnimalAnti-oxidant and anti-inflammatory activities of macelignan in murine hippocampal cell line and primary culture of rat microglial cellsView study →Reference 6Sohn JH et al. · 2008Protective effects of macelignan on cisplatin-induced hepatotoxicity is associated with JNK activationView study →Reference 7Paul S et al. · 2013Multiple biological properties of macelignan and its pharmacological implicationsView study →}, with the CYP2C19 interaction work appearing more recently under “anwuligan” ^{8Reference 8Cheng X et al. · 2026Mechanism-based inactivation of CYP2C19 by anwuligan resulting in changes in pharmacokinetic properties of amitriptylineView study →}. Manufacture today is by extraction/isolation from nutmeg for research-reagent supply; no dominant total-synthesis route is established as the commercial source, and the compound is not manufactured as a marketed supplement.

Patents: not yet researched.

Toxicity & Safety

Macelignan carries a low intrinsic-toxicity flag. Across the preclinical record it was tolerated in the doses used — oral dosing in diabetic mice actually improved metabolic and liver markers ^{2Reference 2Han KL et al. · 2008Therapeutic potential of peroxisome proliferators-activated receptor-alpha/gamma dual agonist with alleviation of endoplasmic reticulum stress for the treatment of diabetesView study →}, and it was protective against chemical liver injury ^{6Reference 6Sohn JH et al. · 2008Protective effects of macelignan on cisplatin-induced hepatotoxicity is associated with JNK activationView study →} — and no isolate-specific acute toxicity, genotoxicity or organ-toxicity signal is reported. Importantly, nutmeg’s well-known toxic and deliriant effects at high doses are attributed to myristicin and related volatile constituents, not to this lignan, so anwuligan should not inherit nutmeg’s toxicity badge.

The real safety consideration is a drug-interaction one rather than direct harm:

Safety at a Glance

✅ Low / no toxicity

• No isolate-specific toxicity reported. Tolerated in the cell and rodent studies conducted to date; several endpoints were protective (liver, metabolic) ^{2,6,7Reference 2Han KL et al. · 2008Therapeutic potential of peroxisome proliferators-activated receptor-alpha/gamma dual agonist with alleviation of endoplasmic reticulum stress for the treatment of diabetesView study →Reference 6Sohn JH et al. · 2008Protective effects of macelignan on cisplatin-induced hepatotoxicity is associated with JNK activationView study →Reference 7Paul S et al. · 2013Multiple biological properties of macelignan and its pharmacological implicationsView study →}.
• CYP2C19 mechanism-based inactivation. Macelignan irreversibly disables CYP2C19 and raised amitriptyline exposure ~30% in animals — a plausible route to interactions with CYP2C19-metabolised drugs (some antidepressants, PPIs, clopidogrel activation, diazepam) ^{8Reference 8Cheng X et al. · 2026Mechanism-based inactivation of CYP2C19 by anwuligan resulting in changes in pharmacokinetic properties of amitriptylineView study →}.
• No human safety data. All evidence is preclinical; oral bioavailability, chronic-dosing safety and reproductive/developmental data for the isolate are uncharacterised.
• Don’t read across from whole nutmeg. Nutmeg’s toxicity is driven by other constituents (myristicin); conversely, the lignan’s clean preclinical profile does not license high-dose nutmeg use.

A reproductive/developmental-toxicity dataset for isolated macelignan does not exist; any pregnancy or lactation decision belongs to the herb or product page where intake is actually decided, not to this molecule page.

Dosage

There is no established human dose for macelignan — it is a research compound, not a marketed supplement. The figures that exist are experimental: the in-vitro anti-cariogenic MIC of 3.9 µg/mL against S. mutans ^{1Reference 1Chung JY et al. · 2006Anticariogenic activity of macelignan isolated from Myristica fragrans (nutmeg) against Streptococcus mutansView study →}, and oral doses used in rodent metabolic and hepatoprotective studies ^{2,6Reference 2Han KL et al. · 2008Therapeutic potential of peroxisome proliferators-activated receptor-alpha/gamma dual agonist with alleviation of endoplasmic reticulum stress for the treatment of diabetesView study →Reference 6Sohn JH et al. · 2008Protective effects of macelignan on cisplatin-induced hepatotoxicity is associated with JNK activationView study →}. These are doses studied in research and are not a personal recommendation.

References

1. Chung JY, Choo JH, Lee MH, Hwang JK (2006). Anticariogenic activity of macelignan isolated from Myristica fragrans (nutmeg) against Streptococcus mutans. Phytomedicine. https://pubmed.ncbi.nlm.nih.gov/16492529/
2. Han KL, Choi JS, Lee JY, Song J, Joe MK, Jung MH, Hwang JK (2008). Therapeutic potential of peroxisome proliferators-activated receptor-alpha/gamma dual agonist with alleviation of endoplasmic reticulum stress for the treatment of diabetes. Diabetes. https://pubmed.ncbi.nlm.nih.gov/18065517/
3. Jin DQ, Lim CS, Hwang JK, Ha I, Han JS (2005). Anti-oxidant and anti-inflammatory activities of macelignan in murine hippocampal cell line and primary culture of rat microglial cells. Biochemical and Biophysical Research Communications. https://pubmed.ncbi.nlm.nih.gov/15883012/
4. Zong K, Liu X, Sun Z, et al. (2020). Macelignan inhibits the inflammatory response of microglia and regulates neuronal survival. Journal of Neuroimmunology. https://pubmed.ncbi.nlm.nih.gov/31838278/
5. Gu L, Cai N, Li M, et al. (2022). Inhibitory effects of macelignan on tau phosphorylation and Aβ aggregation in the cell model of Alzheimer’s disease. Frontiers in Nutrition. https://pubmed.ncbi.nlm.nih.gov/35662922/
6. Sohn JH, Han KL, Kim JH, Rukayadi Y, Hwang JK (2008). Protective effects of macelignan on cisplatin-induced hepatotoxicity is associated with JNK activation. Biological & Pharmaceutical Bulletin. https://pubmed.ncbi.nlm.nih.gov/18239286/
7. Paul S, Hwang JK, Kim HY, Jeon WK, Chung C, Han JS (2013). Multiple biological properties of macelignan and its pharmacological implications. Archives of Pharmacal Research. https://pubmed.ncbi.nlm.nih.gov/23435944/
8. Cheng X, Cheng Z, Dai J, Yang D, Zhang Q, Tang H, Peng Y, Li W, Zheng J (2026). Mechanism-based inactivation of CYP2C19 by anwuligan resulting in changes in pharmacokinetic properties of amitriptyline. Chemical Research in Toxicology. https://pubmed.ncbi.nlm.nih.gov/41968488/

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