Identification of Flavone Glucuronide Isomers by Metal Complexation and Tandem Mass Spectrometry: Regioselectivity of Uridine 5′-Diphosphate–Glucuronosyltransferase Isozymes in the Biotransformation of Flavones

Robotham, Scott A.; Brodbelt, Jennifer S.

doi:10.1021/jf304853j

Cited by 20 publications

(22 citation statements)

References 42 publications

(113 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As previous studies of other flavonoids have shown, 27–29,37 the position of glucuronidation has a strong influence on the CID fragmentation patterns observed. For example, in Figure 3A, a single product, a 7-O-glucuronide, is observed for the reaction of 7-hydroxyflavanone with UGT1A1.…”

Section: Resultssupporting

confidence: 52%

Regiospecificity of Human UDP-glucuronosyltransferase Isoforms in Chalcone and Flavanone Glucuronidation Determined by Metal Complexation and Tandem Mass Spectrometry

Niemeyer

Brodbelt

2013

J. Nat. Prod.

Self Cite

View full text Add to dashboard Cite

The glucuronidation of a series of chalcones (2'-hydroxychalcone, 2',4'-dihydroxychalcone, 3,2'-dihydroxychalcone, 4,2'-dihydroxychalcone, and cardamonin) and their corresponding cyclized flavanones (7-hydroxyflavanone, 3'-hydroxyflavanone, 4'-hydroxyflavanone, and alpinetin) by nine human UDP-glucuronosyltransferase (UGT) 1A enzymes was evaluated. A post-column metal complexation LC-MS/MS strategy was used successfully to produce characteristic mass spectrometric product ions that were utilized in combination with elution order trends to identify chalcone and flavanone monoglucuronides unambiguously, thus allowing determination of the regioselectivities of the UGT1A isoforms. The presence of hydroxy groups on the A or B-ring had a significant effect on the glucuronide product yield and the site where glucuronidation occurred. For example, for reaction with UGT1A9, formation of the 2'-O-glucuronide was increased for dihydroxychalcones with A-ring hydroxy substituents. In contrast, although UGT1A8 reacted with 3,2'-dihydroxychalcone and 4,2'-dihydroxychalcone to yield 2'-O-glucuronide products, the presence of a B-ring hydroxy group at the 4' position on cardamonin and 2',4'-dihydroxychalcone quenched the reaction at the OH-2' position. Moreover, the A-ring OH-4 group promoted glucuronidation at the 2' position for the reaction of 4,2'-dihydroxychalcone with UGT1A1 and 1A3. For UGT1A7, hydroxy group substituents on the chalcone A-ring also promoted cyclization and formation of the corresponding flavanone glucuronide.

show abstract

Section: Resultssupporting

confidence: 52%

Regiospecificity of Human UDP-glucuronosyltransferase Isoforms in Chalcone and Flavanone Glucuronidation Determined by Metal Complexation and Tandem Mass Spectrometry

Niemeyer

Brodbelt

2013

J. Nat. Prod.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Nine components (i.e., peak 1, 2, 4-9, and 12) were identified as gallocatechin, geniposide, luteolin-7-glucoside, Peak 5, 10 and 11 had the same molecular ion [M-H]at m/z 461 and same fragment ions at m/z 284.9, but the different retention time at 19.886 min, 24.362 min, and 27.025 min, respectively. According to the previous results (Borráslinares et al, 2014;Robotham & Brodbelt, 2013;Wang, Lin, Harnly, Harrington, & Chen, 2014), the peak 5 had been identified as luteolin-7-O-β-D-glucuronide and the peak 10 and 11 could be identified as luteolin-5-O-glucuronide, and luteolin-3ʹ-O-glucuronide, respectively.…”

Section: Qualitative Characterization Of Reementioning

confidence: 79%

Antioxidant activity evaluation of rosemary ethanol extract and their cellular antioxidant activity toward HeLa cells

Nie

Wang

et al. 2019

J Food Biochem

View full text Add to dashboard Cite

Rosemary ethanol extract (REE) from Rosmarinus officinalis was identified by LC‐ESI‐MS/MS and 12 compounds were found. Among them, rosmarinic acid (389.78 μg/mg in REE), luteolin‐3ʹ‐O‐glucuronide (325.58 μg/mg), luteolin‐5‐O‐glucuronide (120.92 μg/mg), and geniposide (120.83 μg/mg) are the major components. The antioxidant activity evaluation of REE by off‐line HPLC methods indicated that among the 12 compounds, rosmarinic acid had the strongest scavenging activities in both DPPH· and ·OH. The cytotoxicity experiment showed that REE with the concentration ranges from 1 to 100 µg/ml did not significantly affect the cell viability of HeLa, while inhibitory rate reduced to 62.3% when the concentration was increased to 1,000 µg/ml. The results of intracellular antioxidation assay showed that the ability of REE in reducing the reactive oxygen species (ROS) in HeLa cells was higher than rosmanol, and lower than rosmarinic acid without cell toxicity. Practical applications Plant polyphenols are essential components of functional foods, due to their antioxidant and enzyme inhibition activities. This paper is the first study about the quantification of antioxidant compounds, antioxidant activity evaluation, and their cellular antioxidant activity of polyphenols extract from R. officinalis toward HeLa cells. We aimed to elucidate the chemical composition and recognition of antioxidant components with DPPH and OH free radicals scavenging activity. In addition, the polyphenols dose‐response correlations with cellular antioxidant activity were also determined. These results indicated that off‐line HPLC method with DPPH and OH free radicals as markers is available for screening antioxidant activity of polyphenols from the mixture.

show abstract

“…Considering the foreseeable challenges in glycosylation of the phenolic aglycone, we decided to introduce a monosaccharide unit [56] Botting et al, 2008; [57] Yang & Dai et al, 2016; [58] etc. [71] Brodbelt et al, 2013; [72] Wang & Sun et al, 2015 [73]…”

Section: Synthesis Of Cassiasides C and C2 (75 And 74)mentioning

confidence: 99%

Synthesis of the Diverse Glycosides in Traditional Chinese Medicine

Zhu

2018

Chin. J. Chem.

View full text Add to dashboard Cite

Traditional Chinese medicine (TCM) is a huge treasure trove for the discovery and development of modern pharmaceuticals. Indeed, numerous biologically and pharmacologically significant molecules have been identified from TCM; among them, a considerable portion belongs to glycosides. These glycosides are extremely diverse in structures, consisting of a large variety of aglycones, glycans, as well as glycosidic linkages. In addition, these glycosides occur frequently as a complicated mixture of congeners in the nature sources. This micro‐heterogeneity leads to the isolation of a homogeneous glycoside in an appreciable amount a formidable task. Therefore, development of synthetic approaches toward these nature glycosides has received great attention. In this account, we summarize our twenty‐year efforts spent on this topic. Fifty five representative TCM‐relevant glycosides synthesized by our group are highlighted. Based on the aglycone structure, these glycosides are categorized into three groups, i.e., steroid glycosides, triterpene glycosides, and flavonoid and phenolic glycosides. Typical synthetic approaches are discussed, showing the demanding tactics for regio‐ and stereo‐controlled installation of glycans and overall manipulation of protecting groups. These expedient and scalable synthetic approaches have provided practical alternatives to the accessibility of these TCM components and thus opportunities for their in depth biological and pharmacological studies.

show abstract

Identification of Flavone Glucuronide Isomers by Metal Complexation and Tandem Mass Spectrometry: Regioselectivity of Uridine 5′-Diphosphate–Glucuronosyltransferase Isozymes in the Biotransformation of Flavones

Cited by 20 publications

References 42 publications

Regiospecificity of Human UDP-glucuronosyltransferase Isoforms in Chalcone and Flavanone Glucuronidation Determined by Metal Complexation and Tandem Mass Spectrometry

Regiospecificity of Human UDP-glucuronosyltransferase Isoforms in Chalcone and Flavanone Glucuronidation Determined by Metal Complexation and Tandem Mass Spectrometry

Antioxidant activity evaluation of rosemary ethanol extract and their cellular antioxidant activity toward HeLa cells

Synthesis of the Diverse Glycosides in Traditional Chinese Medicine

Contact Info

Product

Resources

About