| In vitro: |
| Pflugers Arch. 2018 Jun 30. | | Natural and synthetic flavonoids, novel blockers of the volume-regulated anion channels, inhibit endothelial cell proliferation.[Pubmed: 29961148] | Natural flavonoids are ubiquitous in dietary plants and vegetables and have been proposed to have antiviral, antioxidant, cardiovascular protective, and anticancer effects. Volume-regulated anion channels (VRACs), which are essential for cell volume regulation, have been proposed to play a key role in cell proliferation and migration, apoptosis, transepithelial transport, and cancer development.
METHODS AND RESULTS:
In this study, we screened a group of 53 structurally related natural flavonoids and three synthetic flavonoids for their inhibitory activities on VRAC currents. A whole-cell patch technique was used to record VRAC currents in the human embryonic kidney (HEK) 293 and human umbilical vein endothelial (HUVEC) cells. The 5'-bromo-2-deoxyuridine (BrdU) assay technique was used to investigate cell proliferation. At 100 μM, 34 of 53 compounds significantly inhibited hypotonic extrasolution-induced VRAC currents by > 50% in HEK293 cells. Among these compounds, luteolin, baicalein, eupatorin, galangin, quercetin, fisetin, karanjin, Dh-morin, genistein, Irisolidone, and prunetin exhibited the highest efficacy for VRAC blockade (the mean inhibition > 80%) with IC50s of 5-13 μM and Emaxs of about 87-99%. We also studied the effects of three synthetic flavonoids on VRAC currents in HEK293 cells. Flavoxate showed high inhibition efficacy toward VRAC currents (IC50 = 2.3 ± 0.3 μM; Emax = 91.8% ± 2.7%). Finally, these flavonoids inhibited endogenous VRAC currents and cell proliferation in endothelial cells.
CONCLUSIONS:
This study demonstrates that natural and synthetic flavonoids are potent VRAC current inhibitors, and VRAC inhibition by flavonoids might be responsible for their anti-angiogenic effects. | | J Asian Nat Prod Res. 2009 Jun;11(6):471-81. | | Inhibitory activity of isoflavones of Pueraria flowers on nitric oxide production from lipopolysaccharide-activated primary rat microglia.[Pubmed: 20183278 ] | Microglial activation plays an important role in alcohol-induced neuroinflammation. In search for natural medicines that may be of therapeutic potential for alcoholism, two new natural isoflavone glycosides, 6-hydroxybiochanin A-6,7-di-O-beta-d-glucopyranoside (1) and 6-hydroxygenistein-7-O-beta-d-glucopyranoside (2), were isolated from the ethanolic extract of the flowers of Pueraria thomsonii Benth., together with the seven known isoflavones, genistein (3), tectorigenin (4), Irisolidone (5), genistin (7), tectoridin (8), tectorigenin-7-O-beta-d-xylosyl-(1 --> 6)-beta-d-glucopyranoside (9), and 6-hydroxygenistein-6,7-di-O-beta-d-glucopyranoside (11). Moreover, gehuain (6) and kakkalide (10) were obtained from the flowers of Pueraria lobata (Willd.) Ohwi.
METHODS AND RESULTS:
The structures of the new compounds were elucidated by UV, IR, HR-MS, and 1D and 2D NMR spectroscopic methods. Compounds 3-5 substantially inhibited the lipopolysaccharide-induced nitric oxide release from primary cultured rat cortical microglia (IC50: 1.3-9.3 microM). The inhibitory effects of compounds 6, 8, 9, and 11 (IC50: 38-62 microM) were significant but weaker than the above aglycones. However, compounds 1, 2, 7, and 10 showed little inhibitory activity. With regard to the structure-activity relationships of the isoflavonoids for the inhibition of microglial activation, the glycosylation at the C-7 hydroxyl group reduces the inhibitory activity. The methoxylation of 4'-hydroxyl group of 7-glycosylated isoflavonoids reduces the inhibitory activity, while the methoxyl group at the 6-position enhances the activity.
CONCLUSIONS:
The results suggest that isoflavonoids of Pueraria flowers may be of therapeutic potential in alcoholism related to microglial activation. | | Fitoterapia. 2009 Jan;80(1):62-7. | | Protection against neurodegenerative diseases of Iris pseudopumila extracts and their constituents.[Pubmed: 19000749 ] | The present study describes for the first time the in vitro properties of Iris pseudopumila flowers and rhizomes extracts and their constituents.
METHODS AND RESULTS:
The methanolic extract of rhizomes showed significant anti-inflammatory activity through inhibition of NO production in the murine monocytic macrophage cell line RAW 264.7. Among the isolated compounds, those which most effectively inhibited LPS-induced NO production were Irisolidone and 7-methyl-tectorigenin-4'-O-[beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside], with IC(50) values of 23.6 microM and 29.4 microM respectively. Isoorientin and isovitexin exhibited the most promising activity against AChE with IC(50) of 26.8 microM and 36.4 microM, respectively. The same compounds exhibited also the higher activity against BChE. | | Arch Pharm Res. 2008 Jul;31(7):886-90. | | Anti-platelet effects of flavonoids and flavonoid-glycosides from Sophora japonica.[Pubmed: 18704331 ] |
METHODS AND RESULTS:
A methanol extract of Sophora japonica was subjected to anti-platelet activity guided fractionation affording the isolation of four flavonoids and six flavonoid-glycosides: biochanin A (1), Irisolidone (2), genistein (3), sissotrin (4), sophorabioside (5), genistin (6), tectoridin (7), apigenin (8), quercitrin (9), and rutin (10). The structure of each compound was determined by a variety of spectroscopic methods.
CONCLUSIONS:
Among the compounds, 1, 3, and 7 showed approximately 2.5-6.5 fold greater inhibitory effects on arachidonic acid (AA) and U46619 induced platelet aggregation (IC50: 19.9 and 99.8 microM; 20.3 and 53.8 microM; 25.9 and 123.4 microM, respectively) than acetylsalicylic acid (ASA, IC50: 63.0 and 350.0 microM). Compound 2 was an approximately 22-40 fold stronger inhibitor than ASA on AA and U46619 induced aggregation (IC50: 1.6 and 15.6 microM, respectively). | | Planta Med. 2001 Mar;67(2):161-3. | | In vitro anti-Helicobacter pylori activity of irisolidone isolated from the flowers and rhizomes of Pueraria thunbergiana.[Pubmed: 11301866 ] |
METHODS AND RESULTS:
The inhibitory effect of isoflavones isolated from the flowers and rhizomes of Pueraria thunbergiana (Leguminosae) on the growth of Helicobacter pylori (HP) was investigated. Isoflavone glycosides did not inhibit the growth of HP.
However, their aglycones, Irisolidone, tectorigenin and genistein, inhibited HP growth.
CONCLUSIONS:
Among them, Irisolidone had the most potent inhibitory activity against HP and its MIC was 12.5-25 micrograms/ml.
Genistein only weakly inhibited the urease of HP and H+/K(+)-ATPase of rat stomach: its IC50 were 0.43 and 0.89 mg/ml, respectively. |
|
| In vivo: |
| Mol Nutr Food Res. 2017 Feb;61(2). | | Irisolidone attenuates ethanol-induced gastric injury in mice by inhibiting the infiltration of neutrophils.[Pubmed: 27546737] | This study was designed to determine whether Irisolidone and its glycoside kakkalide, which are the major constituents of the flower of Pueraria lobata (Kudzu) can attenuate ethanol-induced gastritic injury in mice.
METHODS AND RESULTS:
Irisolidone and kakkalide inhibited IL-8 secretion and NF-κB activation in lipopolysaccharide-stimulated KATO III cells. Therefore, we investigated their protective effects against ethanol-induced gastric injury in mice. Pretreatment with kakkalide or Irisolidone decreased the area of hemorrhagic ulcerative lesions caused by ethanol and suppressed stomach myeloperoxidase activity, CXCL4 secretion, and NF-κB activation.
The ameliorating effect of Irisolidone was more potent than that of kakkalide.
CONCLUSIONS:
Irisolidone may attenuate ethanol-induced gastritis by inhibiting the infiltration of immune cells, particularly neutrophils, through the regulation of CXCL-4 or IL-8 secretion. | | Biol Pharm Bull. 2005 Mar;28(3):531-3. | | Hepatoprotective effects of irisolidone on tert-butyl hyperoxide-induced liver injury.[Pubmed: 15744084] | To clarify the hepatoprotective effects of kakkalide and its metabolite Irisolidone by human fecal microflora, their effects on tert-butyl hydroperoxide (t-BHP)-injured HepG2 cells and mice were investigated.
METHODS AND RESULTS:
Irisolidone protected HepG2 cells against cytotoxicity induced by t-BHP. However, kakkalide did not protect cytotoxicity. When kakkalide 100 mg/kg was orally administered to mice injured by t-BHP, it significantly inhibited the increase in plasma alanine aminotransferase and aspartate aminotransferase activities by 84% and 85% of t-BHP-treated control group, respectively. The inhibitory effect of kakkalide is much more potent than that of silybin, a hepatoprotective agent. However, intraperitoneally administered kakkalide did not exhibit hepatoprotective activity. When Irisolidone was intraperitoneally administered to mice, it exhibited potent hepatoprotective activity.
CONCLUSIONS:
Based on these findings, Irisolidone can be hepatoprotective and kakkalide may be a prodrug transformed to Irisolidone. |
|
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Sci Adv. 2018 Oct 24;4(10): eaat6994. doi: 10.1126/sciadv.aat6994.IF=12.804(2019)
