The Sunlight Experiment

Compound Monograph

Irigenin

Irigenin is an isoflavone of Iris rhizome (orris) and Belamcanda — the aglycone of iridin — studied preclinically for anti-inflammatory and antioxidant (Nrf2) activity, with no human trials of the isolate. Unlike soy genistein, its estrogen-receptor activity is not well characterised, so it should not be framed as a notable phytoestrogen.

Work in progress

Where Does It Come From? (2)

Irigenin is a naturally occurring isoflavone, found in Iris rhizome and Belamcanda chinensis. It is well tolerated orally (low toxicity).

Belamcanda chinensisIris rhizome

Pharmacology & Research

Irigenin is an Iris-rhizome isoflavone — the aglycone of iridin (iridin = irigenin 7-O-glucoside; the plant glycoside’s synonym “irisin” is unrelated to the human exercise myokine of the same name). Its research is a consistent but entirely preclinical picture of NF-κB/MAPK anti-inflammatory action and Nrf2-mediated cytoprotection across several tissue models. Two disciplines matter: unlike soy genistein, irigenin’s estrogen-receptor activity is not well characterised, so it should not be framed as a notable phytoestrogen; and it should not be silently attributed to blue flag (Iris versicolor), where its occurrence is species-unconfirmed.

What the evidence supports
  • A consistent preclinical anti-inflammatory/antioxidant profile: NF-κB/MAPK suppression and Nrf2/HO-1 activation across lung, joint, retinal, vascular and neuronal models 1,2,5Reference 12023Irigenin attenuates LPS-induced acute lung injury by inactivating MAPK signallingView study →Reference 22024Anti-inflammatory and antioxidant effects of irigenin alleviate osteoarthritis via Nrf2/HO-1View study →Reference 52025In vitroIrigenin alleviates blue-light-induced retinal damage via Nrf2 in vivo and in vitroView study →.
  • The honest headline: no human trials of the isolate; the phytoestrogen angle is weak/uncharacterised (do not equate with soy isoflavones); and human exposure is only incidental, via Iris/Belamcanda preparations.
Evidence by indicationStrength of support
Anti-InflammatoryShaky
32%
Antioxidant / Nrf2Shaky
30%
AnticancerShaky
20%
AntimicrobialUnsupported
16%
1. Anti-inflammatory

Irigenin attenuated LPS-induced acute lung injury by inactivating MAPK signalling 1Reference 12023Irigenin attenuates LPS-induced acute lung injury by inactivating MAPK signallingView study →, modulated blue-light-induced pyroptosis in retinal cells through p38 MAPK and NF-κB 3Reference 32026Irigenin modulates blue-light-induced pyroptosis in retinal pigment epithelial cells through p38 MAPK and NF-κBView study →, and suppressed caspase-3, MMPs and ECM degradation in TNF-α-stimulated nucleus pulposus (disc) cells 4Reference 42021Irigenin reduces caspase-3 and MMPs, suppressing apoptosis and ECM degradation in TNF-α-stimulated nucleus pulposus cellsView study →.

Gap: all in-vitro/rodent, with no human data and effect sizes/achievable concentrations unestablished 1,4Reference 12023Irigenin attenuates LPS-induced acute lung injury by inactivating MAPK signallingView study →Reference 42021Irigenin reduces caspase-3 and MMPs, suppressing apoptosis and ECM degradation in TNF-α-stimulated nucleus pulposus cellsView study →.

2. Antioxidant / Nrf2

Irigenin protects tissues by activating the Nrf2/Keap1 antioxidant pathway: reduced osteoarthritis progression via Nrf2/HO-1 2Reference 22024Anti-inflammatory and antioxidant effects of irigenin alleviate osteoarthritis via Nrf2/HO-1View study →, protection of retina from blue-light 5Reference 52025In vitroIrigenin alleviates blue-light-induced retinal damage via Nrf2 in vivo and in vitroView study → and UVB 6Reference 62024AnimalIrigenin modulates oxidative stress and apoptosis in UVB ocular protection in vivoView study → damage, reduced angiotensin-II oxidative stress in endothelial cells 7Reference 72021Irigenin alleviates angiotensin-II-induced oxidative stress and apoptosis in HUVECs via Nrf2View study → and neuroprotection against MPP+ via Keap1/Nrf2.

Gap: mechanistically consistent but entirely preclinical, and largely a shared isoflavone class effect rather than irigenin-unique 2,5Reference 22024Anti-inflammatory and antioxidant effects of irigenin alleviate osteoarthritis via Nrf2/HO-1View study →Reference 52025In vitroIrigenin alleviates blue-light-induced retinal damage via Nrf2 in vivo and in vitroView study →.

3. Anticancer

Irigenin inhibited glioblastoma progression by suppressing YAP/β-catenin signalling 8Reference 82022Irigenin inhibits glioblastoma progression by suppressing YAP/β-cateninView study →, and a 2025 review compared iridin/irigenin effects in breast, prostate and gastric cancer cell models against known isoflavones 9Reference 92025Effects of iridin and irigenin on cancer (breast/prostate/gastric) versus known isoflavonesView study →.

Gap: thin — few cell-line studies, no in-vivo tumour efficacy for the isolate and no clinical signal 8,9Reference 82022Irigenin inhibits glioblastoma progression by suppressing YAP/β-cateninView study →Reference 92025Effects of iridin and irigenin on cancer (breast/prostate/gastric) versus known isoflavonesView study →.

4. Antimicrobial

Irigenin from Iris confusa acted as a lead against Helicobacter pylori with selective COX-2 and HpIMPDH inhibition 10Reference 102022Irigenin, a novel lead from Iris confusa against Helicobacter pylori with selective COX-2 and HpIMPDH inhibitionView study →, and Iris tectorum small molecules including irigenin inhibited a bacterial histidine kinase to resensitise β-lactam-resistant E. coli 11Reference 112025Iris tectorum small molecules as histidine-kinase inhibitors resensitising β-lactam-resistant E. coliView study →.

Gap: mostly in-vitro enzyme/target assays, with irigenin often one of several actives and no efficacy in animals or humans 10,11Reference 102022Irigenin, a novel lead from Iris confusa against Helicobacter pylori with selective COX-2 and HpIMPDH inhibitionView study →Reference 112025Iris tectorum small molecules as histidine-kinase inhibitors resensitising β-lactam-resistant E. coliView study →.

Mechanisms

Target / pathwayEffectRelevant to
NF-κBinhibitedanti-inflammatory
MAPK (p38 / ERK / JNK)inactivatedanti-inflammatory, acute lung injury
Nrf2 / Keap1 → HO-1activatedcytoprotection (retina/neuro/vascular)
Caspase-3, MMPsdownregulateddisc/joint cell models
YAP / β-cateninsuppressedglioblastoma
COX-2; H. pylori IMPDH; bacterial histidine kinaseinhibitedantimicrobial
UGT1A1 / UGT1A9substrate (glucuronidation)pharmacokinetics

Pharmacokinetics

Irigenin is an isoflavone aglycone and behaves like the class — poor oral bioavailability with extensive phase-II conjugation. It is a confirmed substrate of UGT1A1 and UGT1A9 for glucuronidation in vitro 12Reference 122022In vitroUGT1A1 and UGT1A9 are responsible for the phase-II metabolism of tectorigenin and irigenin in vitroView study →, and it is itself the principal active metabolite of iridin: oral iridin (the glycoside) is hydrolysed to irigenin, whose pharmacokinetics were characterised in rats 13Reference 132021AnimalMetabolite identification of iridin in rats and the pharmacokinetics of its metabolite irigeninView study →. The net picture is low systemic exposure of the free aglycone, heavy glucuronidation, and gut-microbiota-dependent deglycosylation when delivered as iridin — with no human pharmacokinetic data.

Clinical trials

There are no human clinical trials of isolated irigenin (or iridin); all evidence is in-vitro or rodent. Human exposure occurs only incidentally via Iris/Belamcanda (She-gan) herbal preparations, not as a characterised isolate.

CompletedPlannedTerminatedPreclinical
—(none, isolate)——Moderate

Last checked: July 2026.

Toxicity & Safety

Irigenin has a low isolate-toxicity signal — no isolated-compound toxicology, genotoxicity or repeat-dose human data exist, and preclinical studies use it as a protective/anti-inflammatory agent without reported acute toxicity at tested doses. As an isoflavone it carries the generic, weakly-supported theoretical hormonal caveat, but because its ER activity is not well characterised this should not be overstated. For contrast, the parent glycoside iridin (in whole orris/blue-flag rhizome) is associated with the herb’s emetic/purgative, mucous-membrane-irritant action — but that is a whole-rhizome/glycoside property, not demonstrated for purified irigenin.

Pregnancy & lactation

Avoid (isolated supplement). Dietary exposure is not applicable — irigenin is not a meaningful dietary constituent — and as an isolated isoflavone there are no reproductive or developmental safety data, so it is not recommended in pregnancy or lactation (phytoestrogen class membership warrants caution despite weak/uncharacterised ER activity).

Dosage

There is no established human dose — irigenin is not sold or used as a standardised isolate and appears only within Iris/Belamcanda herbal material, so no evidence-based dosage can be given.

References

  1. (2023). Irigenin attenuates LPS-induced acute lung injury by inactivating MAPK signalling. International Immunopharmacology. https://pubmed.ncbi.nlm.nih.gov/36738242/
  2. (2024). Anti-inflammatory and antioxidant effects of irigenin alleviate osteoarthritis via Nrf2/HO-1. Journal of Orthopaedic Surgery and Research. https://pubmed.ncbi.nlm.nih.gov/39458910/
  3. (2026). Irigenin modulates blue-light-induced pyroptosis in retinal pigment epithelial cells through p38 MAPK and NF-κB. Molecular Biotechnology. https://pubmed.ncbi.nlm.nih.gov/41642030/
  4. (2021). Irigenin reduces caspase-3 and MMPs, suppressing apoptosis and ECM degradation in TNF-α-stimulated nucleus pulposus cells. Journal of Orthopaedic Surgery and Research. https://pubmed.ncbi.nlm.nih.gov/34600870/
  5. (2025). Irigenin alleviates blue-light-induced retinal damage via Nrf2 in vivo and in vitro. Cutaneous and Ocular Toxicology. https://pubmed.ncbi.nlm.nih.gov/40013603/
  6. (2024). Irigenin modulates oxidative stress and apoptosis in UVB ocular protection in vivo. Photochemistry and Photobiology. https://pubmed.ncbi.nlm.nih.gov/39232385/
  7. (2021). Irigenin alleviates angiotensin-II-induced oxidative stress and apoptosis in HUVECs via Nrf2. Bioengineered. https://pubmed.ncbi.nlm.nih.gov/33634899/
  8. (2022). Irigenin inhibits glioblastoma progression by suppressing YAP/β-catenin. Frontiers in Pharmacology. https://pubmed.ncbi.nlm.nih.gov/36532767/
  9. (2025). Effects of iridin and irigenin on cancer (breast/prostate/gastric) versus known isoflavones. International Journal of Molecular Sciences. https://pubmed.ncbi.nlm.nih.gov/40141034/
  10. (2022). Irigenin, a novel lead from Iris confusa against Helicobacter pylori with selective COX-2 and HpIMPDH inhibition. RSC Advances. https://pubmed.ncbi.nlm.nih.gov/35794127/
  11. (2025). Iris tectorum small molecules as histidine-kinase inhibitors resensitising β-lactam-resistant E. coli. Frontiers in Microbiology. https://pubmed.ncbi.nlm.nih.gov/39942767/
  12. (2022). UGT1A1 and UGT1A9 are responsible for the phase-II metabolism of tectorigenin and irigenin in vitro. Molecules. https://pubmed.ncbi.nlm.nih.gov/35807350/
  13. (2021). Metabolite identification of iridin in rats and the pharmacokinetics of its metabolite irigenin. Journal of Chromatography B. https://pubmed.ncbi.nlm.nih.gov/34492510/