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 characterized, so it should not be framed as a notable phytoestrogen.
Sources · 2
Where Does It Come From?
Irigenin is a naturally occurring isoflavone, found in Iris rhizome and Belamcanda chinensis. 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.
Irigenin at a Glance
Irigenin is an isoflavone of iris rhizome and Belamcanda — the aglycone of iridin.
Unlike soy isoflavones such as genistein, it is not a notable phytoestrogen, which is worth stating because the isoflavone label usually implies estrogenic activity. Its studied effects are anti-inflammatory and antioxidant through Nrf2 instead.
No human trials of the isolate exist.
What It's Used For
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 characterized, 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.
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.
Irigenin attenuated LPS-induced acute lung injury by inactivating MAPK signaling 1Reference 1Irigenin 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 3Irigenin 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 4Irigenin 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,
Irigenin protects tissues by activating the Nrf2/Keap1 antioxidant pathway: reduced osteoarthritis progression via Nrf2/HO-1 2Reference 2Anti-inflammatory and antioxidant effects of irigenin alleviate osteoarthritis via Nrf2/HO-1View study →, protection of retina from blue-light 5Reference 5In vitroIrigenin alleviates blue-light-induced retinal damage via Nrf2 in vivo and in vitroView study → and UVB 6Reference 6AnimalIrigenin modulates oxidative stress and apoptosis in UVB ocular protection in vivoView study → damage, reduced angiotensin-II oxidative stress in endothelial cells 7Reference 7Irigenin 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,
Irigenin inhibited glioblastoma progression by suppressing YAP/β-catenin signaling 8Reference 8Irigenin 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 9Effects of iridin and irigenin on cancer (breast/prostate/gastric) versus known isoflavonesView study →.
Gap: thin — few cell-line studies, no in-vivo tumor efficacy for the isolate and no clinical signal 8,
Irigenin from Iris confusa acted as a lead against Helicobacter pylori with selective COX-2 and HpIMPDH inhibition 10Reference 10Irigenin, 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 resensitize β-lactam-resistant E. coli 11Reference 11Iris 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,
Mechanisms
| Target / pathway | Effect | Relevant to |
|---|---|---|
| NF-κB | inhibited | anti-inflammatory |
| MAPK (p38 / ERK / JNK) | inactivated | anti-inflammatoryacute lung injury |
| Nrf2 / Keap1 → HO-1 | activated | cytoprotection (retina/neuro/vascular) |
| Caspase-3, MMPs | downregulated | disc/joint cell models |
| YAP / β-catenin | suppressed | glioblastoma |
| COX-2; H. pylori IMPDH; bacterial histidine kinase | inhibited | antimicrobial |
| UGT1A1 / UGT1A9 | substrate (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 12In 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 hydrolyzed to irigenin, whose pharmacokinetics were characterized in rats 13Reference 13AnimalMetabolite 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 characterized isolate.
| Completed | Planned | Terminated | Preclinical |
|---|---|---|---|
| —(none, isolate) | — | — | Moderate |
Last checked: July 2026.
Toxicity & Safety
Irigenin shows no acute toxicity in the preclinical work, and the two cautions people might reach for — a phytoestrogen effect and orris rhizome’s purgative reputation — both apply weakly or not at all to the purified compound.
- No reported acute toxicity. Preclinical studies use it as a protective agent without toxicity at the doses tested.
- Not the rhizome’s irritant principle. The emetic and mucous-membrane-irritant action belongs to whole orris rhizome and its glycoside, not purified irigenin.
- Avoid the isolated supplement in pregnancy and lactation. No reproductive data.
- Hormonal caveat is weak and theoretical. Its estrogen-receptor activity is not well characterized, so the isoflavone class caution should not be overstated.
- No isolate toxicology. No genotoxicity or repeat-dose human data exist.
Full Safety & Interactions Detail
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 characterized 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.
Dosage
There is no established human dose — irigenin is not sold or used as a standardized isolate and appears only within Iris/Belamcanda herbal material, so no evidence-based dosage can be given.
References
- Liu D, Wang Q, Yuan W, et al. (2023). Irigenin attenuates LPS-induced acute lung injury by inactivating MAPK signalling. Hum Exp Toxicol. https://pubmed.ncbi.nlm.nih.gov/36738242/
- Fang X, Zhao H, Xu T, et al. (2024). Anti-inflammatory and antioxidant effects of irigenin alleviate osteoarthritis via Nrf2/HO-1. Pharmaceuticals (Basel). https://pubmed.ncbi.nlm.nih.gov/39458910/
- Su IL, Yeh KL, Lee CY, et al. (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/
- Zhang G, Liao Y, Yang H, et al. (2021). Irigenin reduces caspase-3 and MMPs, suppressing apoptosis and ECM degradation in TNF-α-stimulated nucleus pulposus cells. Chem Biol Interact. https://pubmed.ncbi.nlm.nih.gov/34600870/
- Yeh KL, Kuan YH, Wu SW, et al. (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/
- Yeh KL, Wu SW, Chiang CY, et al. (2024). Irigenin modulates oxidative stress and apoptosis in UVB ocular protection in vivo. Biomed Pharmacother. https://pubmed.ncbi.nlm.nih.gov/39232385/
- Zhang Q, Xue T, Guan J, et al. (2021). Irigenin alleviates angiotensin-II-induced oxidative stress and apoptosis in HUVECs via Nrf2. Bioengineered. https://pubmed.ncbi.nlm.nih.gov/33634899/
- Xu J, Sun S, Zhang W, et al. (2022). Irigenin inhibits glioblastoma progression by suppressing YAP/β-catenin. Frontiers in Pharmacology. https://pubmed.ncbi.nlm.nih.gov/36532767/
- Won Y, Kim HH, Jeong SH, et al. (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/
- Abdel-Baki PM, El-Sherei MM, Khaleel AE, et al. (2022). Irigenin, a novel lead from Iris confusa against Helicobacter pylori with selective COX-2 and HpIMPDH inhibition. Sci Rep. https://pubmed.ncbi.nlm.nih.gov/35794127/
- Ji Y, Wang Y, Xu Z, et al. (2025). Iris tectorum small molecules as histidine-kinase inhibitors resensitising β-lactam-resistant E. coli. Molecules. https://pubmed.ncbi.nlm.nih.gov/39942767/
- Li J, Xu Z, Gu J (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/
- Hu T, Ge X, Wang J, et al. (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/
