Compound Monograph
Arctigenin
Arctigenin is a dibenzylbutyrolactone lignan and the aglycone of arctiin — the most-studied bioactive of burdock seed. Best known preclinically as the first "antiausterity" agent (selectively killing tumor cells under glucose deprivation), with anti-inflammatory, antiviral and metabolic activity; the only human data are early-phase trials of an arctigenin-rich burdock-seed extract, not the pure compound.
Sources · 4
Where Does It Come From?
Arctigenin is a naturally occurring lignan (dibenzylbutyrolactone), found in Burdock — seed/fruit and 3 other sources. It is well tolerated orally (low toxicity).
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.
Arctigenin at a Glance
Arctigenin is a dibenzylbutyrolactone lignan and the most-studied bioactive of burdock seed — the aglycone released from arctiin by gut bacteria.
Its distinction is being the first described “antiausterity” agent: a compound that selectively kills tumour cells under glucose deprivation, exploiting the fact that cancer cells in poorly vascularised tumour cores cannot tolerate starvation the way normal cells can. That is a genuinely different anticancer strategy from cytotoxicity.
It also carries antiviral and anti-inflammatory preclinical work.
What It's Used For
Arctigenin is a dibenzylbutyrolactone lignan — the aglycone of arctiin (its glucoside prodrug) — and the most-studied bioactive of burdock (Arctium lappa) seed, where it concentrates far more than in the root. Its signature is a mechanism: arctigenin was identified as the first “antiausterity” agent, preferentially killing tumor cells under glucose starvation while sparing glucose-fed cells 1Reference 1Identification of arctigenin as an antitumour agent that has the ability to eliminate the tolerance of cancer cells to nutrient starvationView study →.
Two caveats frame everything. First, the only human data come from an arctigenin-rich burdock-seed extract (GBS-01), a multi-component preparation — never from the isolated compound 4Reference 4Phase-I trial of GBS-01 for advanced pancreatic cancer refractory to gemcitabineView study →.
Second, its poor oral bioavailability (extensive first-pass glucuronidation) is the central translational limiter 16Reference 16AnimalExtensive intestinal first-pass elimination of arctigenin in ratsView study →.
Support is an experimental score — weighted by study type (human > animal > in vitro) and volume. A beta, not a validated metric. Human data are limited to an extract program, so isolate scores stay low. Each application links to its write-up.
Arctigenin was the compound that defined antiausterity — selectively killing PANC-1 pancreatic cells under glucose deprivation while sparing glucose-fed cells 1Reference 1Identification of arctigenin as an antitumour agent that has the ability to eliminate the tolerance of cancer cells to nutrient starvationView study → — later extended to STAT3/β-catenin suppression in breast cancer 2Reference 2Arctigenin attenuates breast cancer progression through the GM-CSF/TSLP/STAT3/β-catenin axisView study → and HER2 inhibition with autophagy-linked apoptosis 3Reference 3Arctigenin-mediated cell death of SK-BR-3 cells via HER2 inhibition and autophagy-linked apoptosisView study →. The only human signal is an early-phase trial of GBS-01, an arctigenin-rich burdock-seed extract, in gemcitabine-refractory pancreatic cancer 4Reference 4Phase-I trial of GBS-01 for advanced pancreatic cancer refractory to gemcitabineView study →, with a companion study using plasma lactate as a pharmacodynamic marker 5Reference 5Clinical trialChange in plasma lactate concentration during arctigenin administration in a phase-I clinical trialView study →.
Gap: there is no trial of the isolated compound — GBS-01 is a multi-component extract, single-arm and tiny, so efficacy cannot be attributed to arctigenin alone 4Reference 4Phase-I trial of GBS-01 for advanced pancreatic cancer refractory to gemcitabineView study →.
Arctigenin suppresses iNOS, COX-2 and NF-κB signaling in macrophages 6Reference 6In vitroAnti-inflammatory effects of arctigenin, a lignan from Arctium lappa, in vitroView study → and is the effective anti-colitis constituent over its prodrug arctiin in mice 7Reference 7Arctigenin but not arctiin acts as the major effective constituent of Arctium lappa against colitisView study →, as consolidated in a dedicated PK/efficacy review 8Reference 8Arctigenin: pharmacology, total synthesis, and progress in structure modificationView study →.
Gap: all preclinical, with no human inflammatory-disease endpoint 6,
Arctigenin showed anti-influenza activity in vivo (including in immunocompromized mice) 9,
Gap: no human antiviral data, and the influenza work is older 9,
Arctigenin protected against cerebral ischemia-reperfusion by suppressing neuroinflammation 12Reference 12AnimalArctigenin protects focal cerebral ischemia-reperfusion rats through inhibiting neuroinflammationView study → and produced antidepressant/anxiolytic-like effects on repeated dosing in mice 13Reference 13AnimalRepeated arctigenin treatment produces antidepressant- and anxiolytic-like effects in miceView study →.
Gap: heterogeneous rodent models with no convergent mechanism, and CNS exposure is limited by poor bioavailability 12,
Arctigenin mitigated insulin resistance via IRS2/GLUT4 signaling 14Reference 14Arctigenin mitigates insulin resistance via modulating the IRS2/GLUT4 pathwayView study → and inhibited adipogenesis through AMPK activation, reducing high-fat-diet weight gain 15Reference 15AnimalArctigenin inhibits adipogenesis by inducing AMPK activation and reduces weight gain in high-fat-diet miceView study →.
Gap: rodent-only, with modest effect sizes and no human metabolic trial 14,
Mechanisms
| Target / pathway | Effect | Relevant to |
|---|---|---|
| Cellular “austerity” (glucose deprivation) + AMPK/mTOR | selective cytotoxicity to nutrient-starved tumor cells | anticancer |
| STAT3 / β-catenin; HER2 → autophagy | ↓ proliferation, pro-apoptotic | anticancer (breast) |
| NF-κB (+ iNOS, COX-2) | ↓ pro-inflammatory mediators | anti-inflammatorycolitisneuroinflammation |
| IRS2 / GLUT4; AMPK (anti-adipogenesis) | restored insulin signaling; ↓ lipogenesis | metabolic |
| Viral entry/replication | interferes with influenza and chikungunya | antiviral |
Pharmacokinetics
Poor oral bioavailability is the dominant story. Arctigenin undergoes extensive intestinal first-pass glucuronidation (UGT-mediated), so the parent is largely conjugated before systemic exposure and plasma parent levels are low and short-lived 16,
Clinical trials
The only human data are the GBS-01 extract program — a phase-I dose-finding trial in advanced pancreatic cancer refractory to gemcitabine (tolerability, occasional responses) 4Reference 4Phase-I trial of GBS-01 for advanced pancreatic cancer refractory to gemcitabineView study → and a companion pharmacodynamic study 5Reference 5Clinical trialChange in plasma lactate concentration during arctigenin administration in a phase-I clinical trialView study →. There are no trials of isolated or pure arctigenin for any indication; every human data point traces to the arctigenin-rich extract.
| Completed | Planned | Terminated | Preclinical |
|---|---|---|---|
| Phase-I(GBS-01 extract, pancreatic cancer) | — | — | Extensive(isolate) |
Last checked: July 2026.
Toxicity & Safety
Arctigenin looks clean preclinically, but the entire human safety record is one phase-I oncology trial of an extract — its interaction cautions are mechanism-based rather than observed.
- Low toxicity across rodent efficacy studies. No signal of overt organ toxicity at effective doses.
- Avoid in pregnancy and breastfeeding. No reproductive data, plus phytoestrogen-class and immunomodulatory activity.
- Human safety data come from a cancer population only. “Generally low preclinically” is not proven safe.
- Theoretical UGT interactions. Heavily glucuronidated, so it may interact with UGT substrates or inhibitors.
- Immunosuppressant and antidiabetic overlap. NF-κB suppression and rodent insulin-sensitizing effects imply additive risk.
Full Safety & Interactions Detail
Arctigenin shows low toxicity across the rodent efficacy studies, with no signal of overt organ toxicity at effective doses 6Reference 6In vitroAnti-inflammatory effects of arctigenin, a lignan from Arctium lappa, in vitroView study →, and the GBS-01 phase-I trial established a tolerable dose in cancer patients 4Reference 4Phase-I trial of GBS-01 for advanced pancreatic cancer refractory to gemcitabineView study → — though a measurable rise in plasma lactate during dosing 5Reference 5Clinical trialChange in plasma lactate concentration during arctigenin administration in a phase-I clinical trialView study → is a metabolic effect worth noting rather than an established adverse event. Its interaction profile is theoretical and mechanism-based: as a heavily UGT-glucuronidated molecule it may interact with UGT substrates or inhibitors 16Reference 16AnimalExtensive intestinal first-pass elimination of arctigenin in ratsView study →, its NF-κB-suppressing/immunomodulatory action warrants caution alongside immunosuppressants 6Reference 6In vitroAnti-inflammatory effects of arctigenin, a lignan from Arctium lappa, in vitroView study →, and its rodent insulin-sensitizing effect implies additive risk with antidiabetic drugs 14Reference 14Arctigenin mitigates insulin resistance via modulating the IRS2/GLUT4 pathwayView study →.
Human safety data are confined to a cancer population — “generally low preclinically” is not the same as proven safe.
Dosage
There is no established human dose for isolated arctigenin, and nothing here is a recommendation. The only human dosing reference is the GBS-01 extract, titrated under oncology supervision in the phase-I pancreatic-cancer study — an extract standardized to arctigenin content, not a pure-compound dose 4Reference 4Phase-I trial of GBS-01 for advanced pancreatic cancer refractory to gemcitabineView study →. Preclinical doses are rodent mg/kg figures that do not convert to safe human intake, and any real-world intake comes indirectly from burdock-seed preparations.
References
- Awale S, et al. (2006). Identification of arctigenin as an antitumour agent that has the ability to eliminate the tolerance of cancer cells to nutrient starvation. Cancer Research. https://pubmed.ncbi.nlm.nih.gov/16452235/
- Shi H, et al. (2020). Arctigenin attenuates breast cancer progression through the GM-CSF/TSLP/STAT3/β-catenin axis. International Journal of Molecular Sciences. https://pubmed.ncbi.nlm.nih.gov/32887217/
- Lee MG, et al. (2021). Arctigenin-mediated cell death of SK-BR-3 cells via HER2 inhibition and autophagy-linked apoptosis. Pharmacological Reports. https://pubmed.ncbi.nlm.nih.gov/33677703/
- Ikeda M, et al. (2016). Phase-I trial of GBS-01 for advanced pancreatic cancer refractory to gemcitabine. Cancer Science. https://pubmed.ncbi.nlm.nih.gov/27685612/
- Fujioka R, et al. (2018). Change in plasma lactate concentration during arctigenin administration in a phase-I clinical trial. PLoS One. https://pubmed.ncbi.nlm.nih.gov/29856804/
- Zhao F, et al. (2009). Anti-inflammatory effects of arctigenin, a lignan from Arctium lappa, in vitro. Journal of Ethnopharmacology. https://pubmed.ncbi.nlm.nih.gov/19429312/
- Wu X, et al. (2014). Arctigenin but not arctiin acts as the major effective constituent of Arctium lappa against colitis. International Immunopharmacology. https://pubmed.ncbi.nlm.nih.gov/25284342/
- Wu D, Jin L, Huang X, et al. (2022). Arctigenin: pharmacology, total synthesis, and progress in structure modification. J Enzyme Inhib Med Chem. https://pubmed.ncbi.nlm.nih.gov/36093586/
- Yang Z, et al. (2005). Anti-influenza-virus effect of arctigenin in vivo. Zhong Yao Cai. https://pubmed.ncbi.nlm.nih.gov/16514891/
- Hayashi K, et al. (2010). Therapeutic effect of arctiin and arctigenin in immunocompetent and immunocompromised mice infected with influenza A virus. Biological & Pharmaceutical Bulletin. https://pubmed.ncbi.nlm.nih.gov/20606313/
- Shukla S, et al. (2024). Arctigenin inhibits chikungunya virus entry and replication. Phytomedicine. https://pubmed.ncbi.nlm.nih.gov/38489894/
- Fan T, et al. (2012). Arctigenin protects focal cerebral ischemia-reperfusion rats through inhibiting neuroinflammation. Biological & Pharmaceutical Bulletin. https://pubmed.ncbi.nlm.nih.gov/22972486/
- Du Y, et al. (2019). Repeated arctigenin treatment produces antidepressant- and anxiolytic-like effects in mice. Brain Research Bulletin. https://pubmed.ncbi.nlm.nih.gov/30597190/
- Zhou Y, et al. (2023). Arctigenin mitigates insulin resistance via modulating the IRS2/GLUT4 pathway. International Immunopharmacology. https://pubmed.ncbi.nlm.nih.gov/36481528/
- Han YH, et al. (2016). Arctigenin inhibits adipogenesis by inducing AMPK activation and reduces weight gain in high-fat-diet mice. Journal of Cellular Biochemistry. https://pubmed.ncbi.nlm.nih.gov/26852013/
- Gao Q, et al. (2014). Extensive intestinal first-pass elimination of arctigenin in rats. Journal of Pharmaceutical and Biomedical Analysis. https://pubmed.ncbi.nlm.nih.gov/24434279/
- Wang G, et al. (2023). The therapeutic potential of arctigenin against multiple diseases: a mechanistic review. Phytomedicine. https://pubmed.ncbi.nlm.nih.gov/36628833/
