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

Shi, Ziming; Zhang, Guozhe; Zhao, Lulu; Wang, Shen; Kano, Yoshihiro; Yuan, Dan

doi:10.1007/s13318-014-0202-0

Cited by 13 publications

(11 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nowadays, UHPLC/Q‐TOF–MS is introduced as a commercially available instrument, which has been applied for the pharmaceutical, toxicological and biochemical analyses (Cheng et al, 2012; Li et al, 2010; Shi et al, 2015; Zhang et al, 2015; Zhou et al, 2009). It has the advantages of rapid and efficient separation and detection methods with accurate mass measurement and MS/MS (Zhang et al, 2015).…”

Section: Resultsmentioning

confidence: 99%

Urinary excretion of silibinin diastereoisomers and their conjugated metabolites in rat and human at different dosages

Yuan²,

Pang

et al. 2022

Biomedical Chromatography

Self Cite

View full text Add to dashboard Cite

Silibinin is a mixture of two flavonoid lignan silibinins A and B from the seeds of milk thistle (Silybum marianum L.). Using ultra-performance liquid chromatography/ quadrupole time-of-flight-MS (UPLC/Q-TOF-MS), a total of 18 metabolites were identified in rat and human urine samples after oral administration of silibinin capsule.Furthermore, nine glucuronides and/or sulfated metabolites and two prototype compounds were simultaneously quantified in rat urine after oral administration of silibinin capsule at 50 and 100 mg/kg. Over a 72-h period, 27.6% and 23.3% of silibinin were excreted in the form of metabolites (n = 11) in urine, among which five major metabolites, including silibinin A-7-O-β-glucuronide (SA-7G), silibinin B-7-Oβ-glucuronide (SB-7G), silibinin A-5-O-β-glucuronide (SA-5G), silibinin B-5-Oβ-glucuronide (SB-5G) and silibinin A-20-O-glucuronide (SA-20G), accounted for 20.5% and 15.5% of the dosages, respectively, when administered at doses of 50 and 100 mg/kg. These results suggested that glucuronidation at the C7-, C5-and C20-hydroxyls was the primary metabolic pathway of silibinin diastereoisomers in vivo. The present results provide helpful information about the in vivo metabolism and clinical usage of silibinin capsule.

show abstract

Section: Resultsmentioning

confidence: 99%

Urinary excretion of silibinin diastereoisomers and their conjugated metabolites in rat and human at different dosages

Yuan²,

Pang

et al. 2022

Biomedical Chromatography

Self Cite

View full text Add to dashboard Cite

show abstract

“…In terms of chemical structure, both tectorigenin and irigenin contain phenolic hydroxyl groups, which are very prone to glucuronidation. Previous studies have shown that tectorigenin undergoes extensive phase II metabolism, and that its monoglucuronide conjugate is the major metabolite [14,15]. Irigenin can also be metabolized by UGTs [16].…”

Section: Discussionmentioning

confidence: 99%

“…As standards to determine the metabolite structure were lacking, we made assumptions according to the literature. A previous study indicated that glucuronidation is a key reaction in tectorigenin metabolism, and the concentrations of tectorigenin conjugates in plasma are higher than that of tectorigenin [14,15]. Because tectorigenin-7-O-glucuronide and tectorigenin-7-O-sulfate are the primary metabolites, the C-7 position might be the main site targeted by glucuronidation, even though there are three phenolic hydroxyl groups available.…”

Section: Discussionmentioning

confidence: 99%

“…As the interest in tectorigenin and irigenin increases, it is particularly important to clarify their metabolism in the organism. Previous studies on tectorigenin pharmacokinetics in rats showed that the plasma levels of conjugated tectorigenin metabolites (glucuronide and sulfate) are much higher than that of tectorigenin aglycone [14], and that the concentration of tectorigenin monoglucuronide is higher than that of other metabolites [15]. On the other hand, no studies have investigated the metabolites of irigenin in vivo.…”

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

UGT1A1 and UGT1A9 Are Responsible for Phase II Metabolism of Tectorigenin and Irigenin In Vitro

2022

Molecules

View full text Add to dashboard Cite

Tectorigenin and irigenin are biologically active isoflavones of Belamcanda chinensis (L.) DC. Previous studies indicated that both compounds could be metabolized in vivo; however, the kinetic parameters of enzymes involved in the metabolization of tectorigenin and irigenin have not been identified. The aim of this study was to investigate UGTs involved in the glucuronidation of tectorigenin and irigenin and determine enzyme kinetic parameters using pooled human liver microsomes (HLMs) and recombinant UGTs. Glucuronides of tectorigenin and irigenin were identified using high-performance liquid chromatography (HPLC) coupled with mass spectrometry and quantified by HPLC using a response factor method. The results showed that tectorigenin and irigenin were modified by glucuronidation in HLMs. One metabolite of tectorigenin (M) and two metabolites of irigenin (M1 and M2) were detected. Chemical inhibition and recombinant enzyme experiments revealed that several enzymes could catalyze tectorigenin and irigenin glucuronidation. Among them, UGT1A1 and UGT1A9 were the primary enzymes for both tectorigenin and irigenin; however, the former mostly produced irigenin glucuronide M1, while the latter mostly produced irigenin glucuronide M2. These findings suggest that UGT1A1 and UGT1A9 were the primary isoforms metabolizing tectorigenin and irigenin in HLMs, which could be involved in drug–drug interactions and, therefore, should be monitored in clinical practice.

show abstract

“…In the past decade, the metabolism of PF isoflavanoids in vitro has been reported by some scholars ( Hirayama et al, 2011 ). Our research group have also been devoting our efforts toward their ADME (absorption, distribution, metabolism, and elimination) characteristic by column separation, ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS), and NMR spectroscopy ( Bai et al, 2010 ; Bai et al, 2011a ; Bai et al, 2011b ; Qu et al, 2012 ; Wang H. et al, 2013 ; Wang S. et al, 2013 ; Zhang et al, 2013 ; Qu et al, 2014 ; Shi et al, 2015 ; Zhang et al, 2015 ). A total of ten urinary and biliary metabolites have been isolated and structurally identified, and the plasma pharmacokinetics as well as urinary and biliary excretion of the conjugated metabolites was also determined in rats after oral administration.…”

Section: Introductionmentioning

confidence: 99%

Systematic characterization of Puerariae Flos metabolites in vivo and assessment of its protective mechanisms against alcoholic liver injury in a rat model

Chen

Wei

et al. 2022

Front. Pharmacol.

Self Cite

View full text Add to dashboard Cite

Puerariae Flos, a representative homology plant of medicine and food for alcoholism, has a long history of clinical experience and remarkable curative effect in the treatment of alcoholic liver disease (ALD). However, its effective forms and hepatoprotective mechanisms remain unknown. In the present study, a strategy based on UPLC-QTOF MS combined with mass defect filtering technique was established for comprehensive mapping of the metabolic profile of PF in rat plasma, urine, bile, and feces after oral administration. Furthermore, the absorbed constituents into plasma and bile with a relatively high level were subjected to the network analysis, functional enrichment analysis, and molecular docking to clarify the potential mechanism. Finally, the therapeutic effect of PF on ALD and predicted mechanisms were further evaluated using a rat model of alcohol-induced liver injury and Western blot analysis. In total, 25 prototype components and 82 metabolites, including 93 flavonoids, 13 saponins, and one phenolic acid, were identified or tentatively characterized in vivo. In addition, glucuronidation, sulfation, methylation, hydroxylation, and reduction were observed as the major metabolic pathways of PF. The constructed compound–target–pathway network revealed that 11 absorbed constituents associated with the 16 relevant targets could be responsible for the protective activity of PF against ALD by regulating nine pathways attributable to glycolysis/gluconeogenesis, amino acid metabolism, and lipid regulation as well as inflammation and immune regulation. In addition, four active ingredients (6″-O-xylosyltectoridin, genistein-7-glucuronide-4′-sulfate, tectoridin-4′-sulfate, and 6″-O-xylosyltectoridin-4′-sulfate) as well as two target genes (MAO-A and PPAR-α) were screened and validated to play a crucial role with a good molecular docking score. The present results not only increase the understanding on the effective form and molecular mechanisms of PF-mediated protection against ALD but also promote better application of PF as a supplement food and herbal medicine for the treatment of ALD.

show abstract

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

Cited by 13 publications

References 25 publications

Urinary excretion of silibinin diastereoisomers and their conjugated metabolites in rat and human at different dosages

Urinary excretion of silibinin diastereoisomers and their conjugated metabolites in rat and human at different dosages

UGT1A1 and UGT1A9 Are Responsible for Phase II Metabolism of Tectorigenin and Irigenin In Vitro

Systematic characterization of Puerariae Flos metabolites in vivo and assessment of its protective mechanisms against alcoholic liver injury in a rat model

Contact Info

Product

Resources

About