Arctigenin

Pharmacology & Research

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 tumour cells under glucose starvation while sparing glucose-fed cells ^{1Reference 1Awale S et al. · 2006Identification 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 4Ikeda M et al. · 2016Phase-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 16Gao Q et al. · 2014AnimalExtensive intestinal first-pass elimination of arctigenin in ratsView study →}.

1. Anticancer (antiausterity)

Arctigenin was the compound that defined antiausterity — selectively killing PANC-1 pancreatic cells under glucose deprivation while sparing glucose-fed cells ^{1Reference 1Awale S et al. · 2006Identification 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 2Shi H et al. · 2020Arctigenin attenuates breast cancer progression through the GM-CSF/TSLP/STAT3/β-catenin axisView study →} and HER2 inhibition with autophagy-linked apoptosis ^{3Reference 3Lee MG et al. · 2021Arctigenin-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 4Ikeda M et al. · 2016Phase-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 5Fujioka R et al. · 2018Clinical 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 4Ikeda M et al. · 2016Phase-I trial of GBS-01 for advanced pancreatic cancer refractory to gemcitabineView study →}.

2. Anti-inflammatory

Arctigenin suppresses iNOS, COX-2 and NF-κB signalling in macrophages ^{6Reference 6Zhao F et al. · 2009In 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 7Wu X et al. · 2014Arctigenin but not arctiin acts as the major effective constituent of Arctium lappa against colitisView study →}, as consolidated in a dedicated PK/efficacy review ^{8Reference 8Gao Q et al. · 2018Arctigenin: pharmacology, total synthesis and progress in structure modificationView study →}.

Gap: all preclinical, with no human inflammatory-disease endpoint ^{6,8Reference 6Zhao F et al. · 2009In vitroAnti-inflammatory effects of arctigenin, a lignan from Arctium lappa, in vitroView study →Reference 8Gao Q et al. · 2018Arctigenin: pharmacology, total synthesis and progress in structure modificationView study →}.

3. Antiviral

Arctigenin showed anti-influenza activity in vivo (including in immunocompromised mice) ^{9,10Reference 9Yang Z et al. · 2005AnimalAnti-influenza-virus effect of arctigenin in vivoView study →Reference 10Hayashi K et al. · 2010AnimalTherapeutic effect of arctiin and arctigenin in immunocompetent and immunocompromised mice infected with influenza A virusView study →} and inhibited chikungunya virus entry and replication in vitro ^{11Reference 11Shukla S et al. · 2024Arctigenin inhibits chikungunya virus entry and replicationView study →}.

Gap: no human antiviral data, and the influenza work is older ^{9,11Reference 9Yang Z et al. · 2005AnimalAnti-influenza-virus effect of arctigenin in vivoView study →Reference 11Shukla S et al. · 2024Arctigenin inhibits chikungunya virus entry and replicationView study →}.

4. Neuroprotective

Arctigenin protected against cerebral ischemia-reperfusion by suppressing neuroinflammation ^{12Reference 12Fan T et al. · 2012AnimalArctigenin protects focal cerebral ischemia-reperfusion rats through inhibiting neuroinflammationView study →} and produced antidepressant/anxiolytic-like effects on repeated dosing in mice ^{13Reference 13Du Y et al. · 2019AnimalRepeated 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 ^{12,13Reference 12Fan T et al. · 2012AnimalArctigenin protects focal cerebral ischemia-reperfusion rats through inhibiting neuroinflammationView study →Reference 13Du Y et al. · 2019AnimalRepeated arctigenin treatment produces antidepressant- and anxiolytic-like effects in miceView study →}.

5. Metabolic

Arctigenin mitigated insulin resistance via IRS2/GLUT4 signalling ^{14Reference 14Zhou Y et al. · 2023Arctigenin mitigates insulin resistance via modulating the IRS2/GLUT4 pathwayView study →} and inhibited adipogenesis through AMPK activation, reducing high-fat-diet weight gain ^{15Reference 15Han YH et al. · 2016AnimalArctigenin 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 ^{14,15Reference 14Zhou Y et al. · 2023Arctigenin mitigates insulin resistance via modulating the IRS2/GLUT4 pathwayView study →Reference 15Han YH et al. · 2016AnimalArctigenin inhibits adipogenesis by inducing AMPK activation and reduces weight gain in high-fat-diet miceView study →}.

Mechanisms

Target / pathway	Effect	Relevant to
Cellular “austerity” (glucose deprivation) + AMPK/mTOR	selective cytotoxicity to nutrient-starved tumour cells	anticancer
STAT3 / β-catenin; HER2 → autophagy	↓ proliferation, pro-apoptotic	anticancer (breast)
NF-κB (+ iNOS, COX-2)	↓ pro-inflammatory mediators	anti-inflammatory, colitis, neuroinflammation
IRS2 / GLUT4; AMPK (anti-adipogenesis)	restored insulin signalling; ↓ 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 ^{16,8Reference 16Gao Q et al. · 2014AnimalExtensive intestinal first-pass elimination of arctigenin in ratsView study →Reference 8Gao Q et al. · 2018Arctigenin: pharmacology, total synthesis and progress in structure modificationView study →}. The implication runs through every application above: efficacy likely needs enriched extracts (the GBS-01 rationale), high oral doses, or delivery strategies, and the impressive rodent potencies are not demonstrably reachable from ordinary intake — which comes indirectly from burdock seed (Niu Bang Zi), where arctigenin is concentrated far above the root ^{17Reference 17Wang G et al. · 2023ReviewThe therapeutic potential of arctigenin against multiple diseases: a mechanistic reviewView study →}.

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 4Ikeda M et al. · 2016Phase-I trial of GBS-01 for advanced pancreatic cancer refractory to gemcitabineView study →} and a companion pharmacodynamic study ^{5Reference 5Fujioka R et al. · 2018Clinical 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.

Last checked: July 2026.

Toxicity & Safety

Arctigenin shows low toxicity across the rodent efficacy studies, with no signal of overt organ toxicity at effective doses ^{6Reference 6Zhao F et al. · 2009In 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 4Ikeda M et al. · 2016Phase-I trial of GBS-01 for advanced pancreatic cancer refractory to gemcitabineView study →} — though a measurable rise in plasma lactate during dosing ^{5Reference 5Fujioka R et al. · 2018Clinical 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 16Gao Q et al. · 2014AnimalExtensive intestinal first-pass elimination of arctigenin in ratsView study →}, its NF-κB-suppressing/immunomodulatory action warrants caution alongside immunosuppressants ^{6Reference 6Zhao F et al. · 2009In vitroAnti-inflammatory effects of arctigenin, a lignan from Arctium lappa, in vitroView study →}, and its rodent insulin-sensitising effect implies additive risk with antidiabetic drugs ^{14Reference 14Zhou Y et al. · 2023Arctigenin 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.

Pregnancy & lactation

Avoid. There is no pregnancy or lactation safety data for arctigenin, and as a dibenzylbutyrolactone lignan (a class with mammalian-lignan/phytoestrogen character) with immunomodulatory activity, it should not be used in either.

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 standardised to arctigenin content, not a pure-compound dose ^{4Reference 4Ikeda M et al. · 2016Phase-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