Compound Monograph
Grandisin
Grandisin is a symmetrical tetrahydrofuran (diaryl-furanoid) lignan from Virola surinamensis, Piper solmsianum and other tropical plants. Its notable signal is antiparasitic — trypanocidal and antileishmanial activity in vitro — alongside larvicidal, antinociceptive/anti-inflammatory and antiangiogenic/cytotoxic effects. All evidence is preclinical, with no human trials of the isolate. It is non-psychoactive and chemically separate from the epeña snuff alkaloids.
Sources · 4
Where Does It Come From?
Grandisin is a naturally occurring tetrahydrofuran lignan, found in Virola and 3 other sources. It is well tolerated orally (low toxicity).
Principal source Epeña Virola spp. Herb monograph → 
Source Nutmeg Myristica fragrans Herb monograph → Concentration
Content by Source
Concentrations not reported. No percent-dry-weight or mg/g figures have been published for this compound in its source plants.
Grandisin at a Glance
Grandisin is a symmetrical tetrahydrofuran lignan from Virola surinamensis, Piper solmsianum and other tropical plants.
Its notable signal is antiparasitic — trypanocidal activity against the Trypanosoma cruzi parasite of Chagas disease, and antileishmanial activity, both in vitro.
That is a neglected-disease research line rather than a supplement one, and it is why the compound appears in the literature at all.
What It's Used For
Grandisin is a symmetrical tetrahydrofuran (diaryl-furanoid) lignan — a relative of sesamin and episesamin — from Virola surinamensis, Piper solmsianum and other tropical plants. One provenance point is load-bearing: grandisin is non-psychoactive and must not inherit the epeña (Virola theiodora) snuff’s psychoactivity or legal status — its pharmacology comes from V. surinamensis/Piper, not the snuff. Its genuine hook is antiparasitic (trypanocidal/antileishmanial), with larvicidal, antinociceptive and antiangiogenic signals alongside; all evidence is preclinical, and several of the strongest antiparasitic results are actually synthetic analogues of grandisin.
Support is an experimental score — weighted by study type (human > animal > in vitro) and volume. A beta, not a validated metric. No human isolate data, so scores stay low by design.
Grandisin’s genuine hook. It is one of the trypanocidal tetrahydrofuran lignans of Piper solmsianum 2Reference 2Trypanocidal tetrahydrofuran lignans from the inflorescences of Piper solmsianumView study → and part of the Virola surinamensis twig fraction active against Trypanosoma cruzi in vitro 3Reference 3Flavonoids and lignans from Virola surinamensis twigs and their in-vitro activity against Trypanosoma cruziView study →.
The Virola neolignan series is antileishmanial 4Reference 4Antileishmanial activity of neolignans from Virola species and synthetic analoguesView study →, and grandisin-derived triazolic and isoxazole analogues extend the antileishmanial/antitrypanosomatid activity 7,
Gap: all in-vitro, with no animal efficacy or human data for isolated grandisin — and several of the strongest results are analogues, not grandisin itself 2,
Grandisin is larvicidal against Aedes aegypti larvae 5Reference 5Larvicidal activity of grandisin against Aedes aegyptiView study → and disrupts the development/growth of the blowfly Chrysomya megacephala 6Reference 6Disruption of Chrysomya megacephala growth caused by the lignan grandisinView study →.
Gap: purely entomological (vector/forensic-fly models), with no relevance to human systemic use and no mechanism established 5,
In mice, grandisin dose-dependently reduced acetic-acid writhing, cut inflammatory-phase (formalin) pain and reduced ear edema, without sedation 10Reference 10Antinociceptive and anti-inflammatory activities of grandisin extracted from Virola surinamensisView study →.
Gap: a single study from one lab, with no mechanism defined and no dose-translation or human data 10Reference 10Antinociceptive and anti-inflammatory activities of grandisin extracted from Virola surinamensisView study →.
Grandisin showed cytotoxicity and antiangiogenic activity in vitro, and has been described as a candidate anticancer lignan 1Reference 1Cytotoxicity and antiangiogenic activity of grandisinView study →.
Gap: cytotoxicity is modest and in-vitro only — “anticancer candidate” is an aspiration, not demonstrated efficacy 1Reference 1Cytotoxicity and antiangiogenic activity of grandisinView study →.
Mechanisms
| Target / pathway | Effect | Relevant to |
|---|---|---|
| Trypanosoma cruzi / Leishmania (in vitro) | direct growth inhibition | antiparasitic |
| Trypanothione reductase (diaryl-THF analogues) | inhibition (proposed mechanism) | antiparasitic |
| Insect larval/pupal development | larvicidal / growth disruption | insecticidal |
| Inflammatory & nociceptive response | reduced, no sedation (mechanism undefined) | anti-inflammatory / analgesic |
| Endothelial angiogenesis + tumor-cell viability | antiangiogenic + cytotoxic in vitro | anticancer (preclinical) |
| Human CYP1A2, 2C9, 3A4/5, 2D6, 2E1 | in-vitro inhibition | herb–drug-interaction flag |
Pharmacokinetics
Grandisin is a lipophilic diaryl-tetrahydrofuran lignan with poor aqueous solubility and, by class, low expected oral bioavailability (no measured F). No in-vivo pharmacokinetics have been published; what exists is in-vitro metabolism only — human liver microsomes extensively metabolize (−)-grandisin via phase-I oxidative routes (O-demethylation/hydroxylation of the trimethoxyphenyl rings), consistent with rapid hepatic first-pass turnover 11Reference 11In-vitro metabolism study of the promising anticancer agent, the lignan (−)-grandisinView study →. Because grandisin both inhibits major CYPs 12Reference 12In-vitro inhibition of human CYP450s 1A2, 2C9, 3A4/5, 2D6 and 2E1 by grandisinView study → and is a CYP substrate, it carries a herb–drug-interaction flag, and its pharmacokinetics are inferred/in-vitro rather than characterized in humans or animals.
Clinical trials
There are no clinical trials of isolated grandisin — no registered or published human studies — and all evidence is in-vitro or rodent/insect preclinical.
| Completed | Planned | Terminated | Preclinical |
|---|---|---|---|
| —(none, isolate) | — | — | Modest(antiparasitic-led) |
Last checked: July 2026.
Toxicity & Safety
No adverse signals have appeared, but the isolate has never been formally tested — and the same activities that make it interesting (insecticidal, antiangiogenic, pan-CYP inhibition) are the reasons for caution.
- No adverse signals reported. The rodent antinociception study found activity without sedation.
- Avoid in pregnancy and lactation. No reproductive data, plus antiangiogenic and insecticidal activity.
- No toxicology of the isolate. No acute-toxicity, genotoxicity or repeat-dose studies exist, so the low rating is analogy, not proven safety.
- Pan-CYP inhibitor in vitro. Carries a herb-drug-interaction flag with co-administered CYP substrates.
- Deliberately insecticidal and cytotoxic. Larvicidal and antiangiogenic activity in vitro are theoretical cautions worth naming.
Full Safety & Interactions Detail
Grandisin has a low intrinsic-toxicity signal that is formally uncharacterized — the rodent antinociception study reported activity without sedation 10Reference 10Antinociceptive and anti-inflammatory activities of grandisin extracted from Virola surinamensisView study →, but no acute-toxicity, genotoxicity or repeat-dose studies of the isolate exist, so low reflects analogy to other dietary lignans and the absence of adverse signals rather than proven safety. Two theoretical cautions belong on the page: grandisin is deliberately larvicidal/insecticidal 5,
Dosage
There is no established human or therapeutic dose — all figures in the literature are in-vitro concentrations or rodent/insect experimental doses, and there is no basis for a human dose.
References
- Valadares MC, de Carvalho IC, de Oliveira Junior L, et al. (2009). Cytotoxicity and antiangiogenic activity of grandisin. Journal of Pharmacy and Pharmacology. https://pubmed.ncbi.nlm.nih.gov/19958595/
- Martins RC, Lago JH, Albuquerque S, et al. (2003). Trypanocidal tetrahydrofuran lignans from the inflorescences of Piper solmsianum. Phytochemistry. https://pubmed.ncbi.nlm.nih.gov/12943793/
- Lopes NP, Chicaro P, Kato MJ, et al. (1998). Flavonoids and lignans from Virola surinamensis twigs and their in-vitro activity against Trypanosoma cruzi. Planta Medica. https://pubmed.ncbi.nlm.nih.gov/9810278/
- Barata LE, Santos LS, Ferri PH, et al. (2000). Antileishmanial activity of neolignans from Virola species and synthetic analogues. Phytochemistry. https://pubmed.ncbi.nlm.nih.gov/11130669/
- Cabral MM, Alencar JA, Guimarães AE, et al. (2009). Larvicidal activity of grandisin against Aedes aegypti. Journal of the American Mosquito Control Association. https://pubmed.ncbi.nlm.nih.gov/19432075/
- Nogueira CD, de Mello RP, Kato MJ, et al. (2009). Disruption of Chrysomya megacephala growth caused by the lignan grandisin. Journal of Medical Entomology. https://pubmed.ncbi.nlm.nih.gov/19351078/
- Costa EC, Cassamale TB, Carvalho DB, et al. (2016). Antileishmanial activity and SAR of triazolic compounds derived from the neolignans grandisin, veraguensin and machilin G. Molecules. https://pubmed.ncbi.nlm.nih.gov/27331807/
- Trefzger OS, das Neves AR, Barbosa NV, et al. (2019). Design, synthesis and antitrypanosomatid activities of 3,5-diaryl-isoxazole analogues based on veraguensin, grandisin and machilin G. Chemical Biology & Drug Design. https://pubmed.ncbi.nlm.nih.gov/30354012/
- Hartmann AP, de Carvalho MR, Bernardes LSC, et al. (2017). Synthesis and 2D-QSAR of neolignan-based diaryl-tetrahydrofuran analogues active against T. cruzi; trypanothione-reductase assessment. European Journal of Medicinal Chemistry. https://pubmed.ncbi.nlm.nih.gov/28926763/
- Carvalho AA, Galdino PM, Nascimento MV, et al. (2010). Antinociceptive and anti-inflammatory activities of grandisin extracted from Virola surinamensis. Phytotherapy Research. https://pubmed.ncbi.nlm.nih.gov/19468987/
- Messiano GB, Santos RA, Ferreira Lde S, et al. (2013). In-vitro metabolism study of the promising anticancer agent, the lignan (−)-grandisin. Journal of Pharmaceutical and Biomedical Analysis. https://pubmed.ncbi.nlm.nih.gov/22995290/
- Habenschus MD, Moreira FL, Lopes NP, et al. (2017). In-vitro inhibition of human CYP450s 1A2, 2C9, 3A4/5, 2D6 and 2E1 by grandisin. Planta Medica. https://pubmed.ncbi.nlm.nih.gov/28073119/
