Irisolidone

The herbs of Pueraia lobata

Pharmacokinetics of irisolidone and its main metabolites in rat plasma determined by ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry.[Pubmed:26465087]

J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Nov 15;1005:23-9.

Irisolidone, a major isoflavone found in Pueraria lobata flowers, exhibits a wide spectrum of bioactivities, while its metabolic pathways and the pharmacokinetics of its metabolites in vivo have not been investigated yet. In the present study, an ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF MS) method was employed to investigate the metabolic pathways of Irisolidone and the pharmacokinetics of its main metabolites in rats, after a single 100mg/kg oral dose of Irisolidone. Protein precipitation method was used to prepare plasma samples. A total of 15 metabolites included Irisolidone were detected and tentatively identified based on the mass spectral fragmentation patterns, elution order or confirmed using available reference standards. The pharmacokinetics of the main metabolites included three glucuronide metabolites tectorigenin-7-O-glucuronide (Te-7G), 6-hydroxybiochanin A-6-O-glucuronide (6-OH-BiA-6G), Irisolidone-7-O-glucuronide (Ir-7G), and three sulfate metabolite tectorigenin-7-O-sulfate-4'-O-sulfate (Te-7S-4'S), tectorigenin-7-O-sulfate (Te-7S) and Irisolidone-7-O-sulfate (Ir-7S), and aglycone tectorigenin (Te), and Irisolidone (Ir) were evaluated. The plasma concentrations reached maximal values of 0.297mumol/L at 10.3h for Te-7S-4'S, 0.199mumol/L at 21.7h for Te-7G, 0.154mumol/L at 8.00h for Te-7S, 4.10mumol/L at 15.3h for 6-OH-BiA-6G, 10.7mumol/L at 9.71h for Ir-7G, 0.918mumol/L at 11.3h for Te, 0.150mumol/L at 8.67h for Ir-7S, and 0.843mumol/L at 9.67h for Ir, respectively. Since the total plasma concentrations of conjugated metabolites were much higher than that of the Irisolidone aglycone, an extensive phase II metabolism plays an important role in the pharmacokinetics of Irisolidone in vivo.

Metabolic profile of irisolidone in rats obtained by ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry.[Pubmed:24184829]

J Chromatogr B Analyt Technol Biomed Life Sci. 2013 Dec 15;941:1-9.

Irisolidone, a major isoflavone found in Pueraria lobata flowers, exhibits a wide spectrum of bioactivities, while its metabolic pathway in vivo has not been investigated. In this study, an ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF MS) method was employed to investigate the in vivo metabolism of Irisolidone in rats. Plasma, bile, urine, and feces were collected from rats after a single 100mg/kg oral dose of Irisolidone. Protein precipitation, solid phase extraction (SPE) and ultrasonic extraction were used to prepare samples of plasma, bile/urine, and feces, respectively. A total of 46 metabolites were detected and tentatively identified based on the mass spectral fragmentation patterns, elution order or confirmed using available reference standards. The metabolic pathways of Irisolidone in rats included decarbonylation, reduction, demethylation, demethoxylation, dehydroxylation, hydroxylation, sulfation, and glucuronidation. The relative content of each metabolite was also determined to help understand the major metabolic pathways of Irisolidone in rats.

Irisolidone attenuates ethanol-induced gastric injury in mice by inhibiting the infiltration of neutrophils.[Pubmed:27546737]

Mol Nutr Food Res. 2017 Feb;61(2).

SCOPE: 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-kappaB 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-kappaB activation. The ameliorating effect of Irisolidone was more potent than that of kakkalide. CONCLUSION: 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.

Excretion of tectoridin metabolites in rat urine and bile orally administrated at different dosages and their inhibitory activity against aldose reductase.[Pubmed:25256063]

Fitoterapia. 2014 Dec;99:99-108.

This study investigated the urinary and biliary excretion of tectoridin, a major active isoflavonoid found in the flowers of Pueraria thomsonii Benth. and the rhizomes of Belamcanda chinensis (L.) DC. Using UHPLC/Q-TOFMS, seven glucuronides and/or sulfated metabolites and four Phase I metabolites were simultaneously quantified in rat urine after oral administration of tectoridin at 100 and 200 mg/kg. Over a 72-h period, 14.2% and 14.7% of the tectoridin were excreted as eleven metabolites in urine, among which, two major metabolites tectorigenin-7-O-beta-D-glucuronide (Te-7G) and tectorigenin accounted for 5.5-5.5% and 4.3-4.4%. Furthermore, the cumulative excretion of four glucuronides and sulfated metabolites in bile accounted for 7.3% and 3.9% of the dose within 60 h, among which, Te-7G and tectorigenin-7-O-glucuronide-4'-O-sulfate (Te-7G-4'S) accounted for 2.3-3.0% and 1.4-3.9%, respectively. The results indicate that the urine was the primary elimination route, and glucuronidation after deglycosylation at C-7 position was the major metabolic pathway of tectoridin in vivo. Moreover, the inhibitory activities of tectoridin and its five metabolites on rat lens aldose reductase were confirmed (IC(5)(0): 1.4-15.5 muM), whereas Irisolidone-7-O-glucuronide (Ir-7G) and Irisolidone showed little activity.

Screening for in vitro metabolites of kakkalide and irisolidone in human and rat intestinal bacteria by ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry.[Pubmed:24412694]

J Chromatogr B Analyt Technol Biomed Life Sci. 2014 Feb 1;947-948:117-24.

Kakkalide and Irisolidone, the main isoflavones of Flos Puerariae, exhibit a wide spectrum of bioactivities. Intestinal bacteria biotransformation plays an important role in the metabolic pathways of flavones, and is directly related to the bioactivities of the prodrugs after oral administration. To the best of our knowledge, the metabolic pathways of kakkalide and Irisolidone in vitro have not been comprehensively studied yet. This paper describes the strategy using ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF MS) for the rapid analysis of the metabolic profiles of kakkalide and Irisolidone after incubated with human and rat intestinal bacteria. Bacteria incubated samples were prepared and analyzed after incubated under anaerobic conditions for 48 h. A total of 17 metabolites, including parent compounds, were detected in human and rat intestinal bacteria incubated samples. The results obtained indicate that hydrolysis, dehydroxylation, demethoxylation, demethylation, hydroxylation, decarbonylation, and reduction were the detected metabolic pathways of kakkalide and Irisolidone in vitro. The conversion rate of Irisolidone in human and rat bacteria was 8.57% and 6.51%, respectively. Biochanin A was the relatively main metabolite of Irisolidone, and the content of biochanin A in human and rat bacteria was 3.68% and 4.25%, respectively. The conversion rate of kakkalide in human and rat bacteria was 99.92% and 98.58%, respectively. Irisolidone was the main metabolite of kakkalide, and the content of Irisolidone in human and rat bacteria was 89.58% and 89.38%, respectively. This work not only provides the evidence of kakkalide and Irisolidone metabolites in vivo, but also demonstrates a simple, fast, sensitive, and inexpensive method for identification of metabolites of other compounds transformed by intestinal bacteria.

Excretion of tectorigenin in rat urine orally administrated at different dosages by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry.[Pubmed:24789580]

Eur J Drug Metab Pharmacokinet. 2015 Sep;40(3):255-66.

Tectorigenin (Te) is a main active component in the flowers of Pueraria thomsonii Benth. and the rhizomes of Belamcanda chinensis (L.) DC. Previously, we have reported the pharmacokinetic properties of Te in rat plasma. The purpose of this study was to investigate the urinary excretion of Te after oral administration to rats at different dose levels. Using UHPLC/Q-TOFMS, totally 26 metabolites were detected in rat urine after oral administration of Te at dose of 65 and 130 mg/kg. Among them, nine metabolites, Te, tectorigenin-7-O-glucuronide-4'-sulfate (Te-7G-4'S), tectorigenin-7-O-glucuronide (Te-7G), tectorigenin-7-O-sulfate (Te-7S), tectorigenin-4'-O-glucuronide (Te-4'S), isotectorigenin, genistein, Irisolidone-7-O-glucuronide (Ir-7G), and Irisolidone, were identified by comparing the retention time, UV and MS spectra with those of authentic standards. A UHPLC/Q-TOFMS method for simultaneous quantification and semi-quantification of all the metabolites in urine was developed. The cumulative urinary excretions of Te and the major metabolite Te-7G were 1.99 and 5.80 mumol at 65 mg/kg, 3.05 and 6.48 mumol at 130 mg/kg, accounted for 4.17 % and 15.8, 2.81 and 9.49 % of administrated Te, respectively. The excretion rates of Te-7G, Te-7G-4'S, Ir-7G, and Te reached a maximum between 12 and 24 h after oral dosing at 65 and 130 mg/kg. The cumulative urine excretion rates of Te were 23.1 and 20.1 % within 72 h at 65 and 130 mg/kg, respectively. These results suggested that the glucuronidation was the primary metabolic pathway especially at low dose level.

8-Hydroxyirilone 5-methyl ether and 8-hydroxyirilone, new antioxidant and alpha-amylase inhibitors isoflavonoids from Iris germanica rhizomes.[Pubmed:28069265]

Bioorg Chem. 2017 Feb;70:192-198.

Iris species are well recognized as wealthy sources of isoflavonoids. In the present study, phytochemical investigation of the rhizomes of Iris germanica (Iridaceae) procure the isolation of two new isoflavonoids namely, 8-hydroxyirilone 5-methyl ether (2) and 8-hydroxyirilone (3), along with eight known isoflavonoids: irilone 4'-methyl ether (1), irilone (4), Irisolidone (5), irigenin S (6), irigenin (7), irilone 4'-O-beta-d-glucopyranoside (8), iridin S (9), and iridin (10). The isolated flavonoids were structurally characterized with the assist of comprehensive spectroscopic analyses (UV, IR, 1D and 2D NMR, and HRMS) and comparing with the published data. They were estimated for their antioxidant and antidaibetic capacities using DPPH and alpha-amylase inhibition assays, respectively. Compounds 2, 3, and 4 exhibited prominent antioxidant activities with IC50 values of 12.92, 9.23, and 10.46muM, respectively compared to propyl gallate (IC50 7.11muM). Moreover, 2-5 possessed highest alpha-amylase inhibitory activity with % inhibition 66.1, 78.3, 67.3, and 70.1, respectively in comparison to acarbose (reference alpha-amylase inhibitor). Additionally, their structure-activity relationship has been discussed.

Irisolidone is a major isoflavone found in Pueraria lobata flowers. Irisolidone exhibits potent hepatoprotective activity. Irisolidone shows the high efficacy for volume-regulated anion channels (VRAC) blockade.

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