Irigenin

Sci Rep. 2016 Nov 16;6:37151.

Irigenin, a novel lead from Western Himalayan chemiome inhibits Fibronectin-Extra Domain A induced metastasis in Lung cancer cells.[Pubmed: 27849000 ]

Several lines of evidence indicate that Fibronectin Extra Domain A (EDA) promotes metastatic capacity of tumor cells by engaging cell surface α9β1 integrins. This interaction mediated by the C-C loop of EDA activates pro-oncogenic signaling pathways leading to epithelial to mesenchymal transition (EMT) of tumor cells, thus signifying its importance in control of metastatic progression.
METHODS AND RESULTS:
In this context the present study was designed to explore the active compounds from selected ethno-medicinal plants of western Himalayan region for targeting EDA of Fibronectin in lung carcinoma cells. Structure based informatics for drug designing and screening was employed to generate a lead compound(s) feed that were conformationally and energetically viable. Out of 120 compounds selected, Irigenin showed best binding-affinity with C-C loop of EDA. Irigenin specifically targeted α9β1 and α4β1 integrin binding sites on EDA comprising LEU46, PHE47, PRO48, GLU58, LEU59 and GLN60 in its C-C loop as evaluated by energy decomposition per residue of Irigenin-EDA complex. In-vitro cell motility assays complemented with EDA knock-in and knockdown assays distinctively demonstrated that Irigenin prevents metastatic capacity of lung cancer cells by selectively blocking EDA.
CONCLUSIONS:
The results presented thus project Irigenin as a lead compound to overcome Fibronectin EDA induced metastatic progression in lung carcinoma cells.

Life Sci. 2006 Apr 11;78(20):2336-42.

Inhibitory effects of Irigenin from the rhizomes of Belamcanda chinensis on nitric oxide and prostaglandin E(2) production in murine macrophage RAW 264.7 cells.[Pubmed: 16307761 ]

METHODS AND RESULTS:
In the present study, we investigated antiinflammatory effects of six flavonoids isolated from the rhizomes of Belamcanda chinensis (Iridaceae) in RAW 264.7 macrophages. The results indicated that Irigenin concentration dependently inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin (PG) E(2) production. Furthermore, this compound inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 proteins and mRNAs without an appreciable cytotoxic effect. Treatment of the transfectant RAW 264.7 cells with Irigenin reduced the level of nuclear factor-kappaB (NF-kappaB) activity, also effectively lowered NF-kappaB binding measured by electrophoretic mobility shift assay (EMSA), which was associated with decreased p65 protein levels in the nucleus. On the basis of the above data, we suggest that the effect of Irigenin in decreasing LPS-induced NO and PGE(2) synthesis is due to diminish the mRNA and protein expression of iNOS and COX-2, respectively, also may be due to under the suppression of NF-kappaB activation.
CONCLUSIONS:
Therefore, Irigenin isolated from the rhizomes of Belamcanda chinensis could be offered as a leading compound for anti-inflammation.

Planta Med. 2003 Jan;69(1):15-20.

Cancer chemopreventive in vitro activities of isoflavones isolated from Iris germanica.[Pubmed: 12567273 ]

METHODS AND RESULTS:
Six known isoflavones were isolated from the rhizomes of Iris germanica, and were established by UV, MS and NMR techniques as irisolidone (1), irisolidone 7-O-alpha-D-glucoside (1a), Irigenin (2), irilone (3), iriflogenin (4), and iriskashmirianin (5). These compounds were examined for their cancer chemopreventive potential. They were shown to be potent inhibitors of cytochrome P450 1A activity with IC 50 values in the range 0.25-4.9 microM. The isoflavones 2, 3 and 5 displayed moderate activity as inducers of NAD(P)H:quinone reductase (QR) in cultured mouse Hepa 1c1c7 cells, with CD values (concentration required to double the specific activity of QR) of 3.5-16.7 microM, whereas weak activity was observed with compounds 4 and 5 in the radical (DPPH) scavenging bioassay (IC 50 values 89.6 and 120.3 microM, respectively).
CONCLUSIONS:
With respect to anti-tumor promoting potential based on anti-inflammatory mechanisms, none of the compounds demonstrated significant activity in the concentration range tested.

J Sep Sci. 2017 Jun;40(12):2565-2574.

Ionic-liquid-based ultrasound-assisted extraction of isoflavones from Belamcanda chinensis and subsequent screening and isolation of potential α-glucosidase inhibitors by ultrafiltration and semipreparative high-performance liquid chromatography.[Pubmed: 28444982 ]

The separation of a compound of interest from its structurally similar homologues to produce high-purity natural products is a challenging problem.
METHODS AND RESULTS:
This work proposes a novel method for the separation of iristectorigenin A from its structurally similar homologues by ionic-liquid-based ultrasound-assisted extraction and the subsequent screening and isolation of potential α-glucosidase inhibitors via ultrafiltration and semipreparative high-performance liquid chromatography. Ionic-liquid-based ultrasound-assisted extraction was successfully applied to the extraction of tectorigenin, iristectorigenin A, Irigenin, and irisflorentin from Belamcanda chinensis. The optimum conditions for the efficient extraction of isoflavones were determined as 1.0 M 1-ethyl-3-methylimidazolium tetrafluoroborate with extraction time of 30 min and a solvent to solid ratio of 30 mL/g. Ultrafiltration with liquid chromatography and mass spectrometry was applied to screen and identify α-glucosidase inhibitors from B. chinensis, followed by the application of semipreparative high-performance liquid chromatography to separate and isolate the active constituents. Four major compounds including tectorigenin, iristectorigenin A, Irigenin, and irisflorentin were screened and identified as α-glucosidase inhibitors, and then the four active compounds abovementioned were subsequently isolated by semipreparative high-performance liquid chromatography (99.89, 88.97, 99.79, and 99.97% purity, respectively).
CONCLUSIONS:
The results demonstrate that ionic liquid extraction can be successfully applied to the extraction of isoflavones from B. chinensis.