Glucuronides of Tea Catechins: Enzymology of Biosynthesis and Biological Activities

Lu, Hongcheng; Meng, Xiaofeng; Li, Chuan; Sang, Shengmin; Patten, Christopher; Sheng, Shuqun; Hong, Jungil; Bai, Naisheng; Winnik, Bozena; Ho, Chi‐Tang; Yang, Chung S.

doi:10.1124/dmd.31.4.452

Cited by 199 publications

(159 citation statements)

References 30 publications

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“…Theasinensin A, 4"-methyl EGCG, and 4"-glucuronyl EGCG were synthesized previously in our laboratory [14][15][16]. Their structures were confirmed by 1 H, 13 C, and 2D NMR.…”

Section: Methodsmentioning

confidence: 99%

“…However, no EGCG autoxidation products were detected in the plasma samples from EGCG-treated mice. We have previously identified 4″-methyl EGCG as the major mono-methylated metabolite of EGCG in mice and 4″-glucuronyl EGCG as the major mono-glucuronide metabolite of EGCG in human, mouse, and rat microsomes [15,16]. In order to further confirm that 4″-glucuronyl EGCG was the major mono-glucuronide metabolite of EGCG in mouse plasma, we compared the LC/MS/MS spectrum of the standard 4″-glucuronyl EGCG with that of the corresponding peak in the plasma samples from EGCG-treated mice.…”

Section: Metabolite Profiles Of Egcg In the Plasma Samples From Egcg-mentioning

confidence: 99%

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Autoxidative quinone formation in vitro and metabolite formation in vivo from tea polyphenol (-)-epigallocatechin-3-gallate: Studied by real-time mass spectrometry combined with tandem mass ion mapping

Sang

Yang

Buckley

et al. 2007

Free Radical Biology and Medicine

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133

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Abstract(−)-Epigallocatechin-3-gallate (EGCG), the most abundant and biologically active compound in tea, has been proposed to have beneficial health effects, including prevention of cancer and heart disease. Different mechanisms of action of EGCG have been proposed, based mainly on studies in cell line systems, in which EGCG is not stable. It has been proposed that oxidation of EGCG and its production of reactive oxygen species are responsible for the biological activities such as receptor inactivation and telomerase inhibition. It is unclear, however, if this phenomenon occurs in vivo. In the present study, the stability of EGCG and product formation in Tris-HCl buffer was investigated using realtime mass spectrometry combined with tandem mass ion mapping. With real-time mass data acquisition, we demonstrate for the first time the formation of EGCG quinone, EGCG dimer quinone, and other related compounds. The structural information of the major appearing ions was provided by tandem mass analysis of each ion. A mechanism for the autoxidation of EGCG was proposed based on the structural information of these ions. None of these oxidation products were observed in the plasma samples of mice after treatment with 50 mg/kg EGCG, i.p. daily for 3 days. Instead, the methylated and conjugated metabolites of EGCG were observed. Therefore the roles of EGCG autoxidation in the biological activities of this compound in vivo remain to be investigated further.

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“…Theasinensin A, 4"-methyl EGCG, and 4"-glucuronyl EGCG were synthesized previously in our laboratory [14][15][16]. Their structures were confirmed by 1 H, 13 C, and 2D NMR.…”

Section: Methodsmentioning

confidence: 99%

Section: Metabolite Profiles Of Egcg In the Plasma Samples From Egcg-mentioning

confidence: 99%

Autoxidative quinone formation in vitro and metabolite formation in vivo from tea polyphenol (-)-epigallocatechin-3-gallate: Studied by real-time mass spectrometry combined with tandem mass ion mapping

Sang

Yang

Buckley

et al. 2007

Free Radical Biology and Medicine

Self Cite

133

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“…In fact, resveratrol experiences such rapid sulfation and glucuronidation by the liver that plasma levels in humans are non-detectable within minutes after consumption (97). EGCG also goes through extensive phase II metabolism including glucuronidation and methylation (98,99). These modifications prevent tissue penetration and accelerate clearance from the plasma (99).…”

Section: The Lung Bioavailability Of Exogenous Antioxidantsmentioning

confidence: 99%

The pharmokinetic limitations of antioxidant treatment for COPD

Foronjy

Wallace

DʼArmiento

2008

Pulmonary Pharmacology & Therapeutics

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COPD is one of the leading causes of death worldwide and the age-adjusted mortality for this disease has risen significantly over the past thirty years. Current pharmacological treatments do not effectively address the inflammatory and apoptotic mechanisms that are critical in the development of this disease. Thus, despite therapy, patients typically experience a continued deterioration of their clinical status. Markers of oxidative stress are increased in the lungs of COPD patients and epidemiologic and animal studies indicate that antioxidants can protect the lungs from the damaging effects of cigarette smoke. To date, however, clinical trials of antioxidants for COPD have yielded disappointing results. This review discusses the pharmokinetic factors that limit the use of exogenous antioxidants as a treatment for this disease. In addition, it addresses strategies to overcome these limitations so that the beneficial properties of antioxidants can be translated into effective therapies for COPD patients. KeywordsAntioxidants; Chronic Obstructive Pulmonary Disease; Emphysema; Inflammation; Cigarette Smoke; Bioavailability Limitations of current pharmacotherapeutic agents in the treatment of COPDChronic Obstructive pulmonary disease (COPD) affects 13.5 million Americans(1) and now ranks as the fourth leading cause of death nationwide. While great strides have been made in the treatment of cardiovascular diseases, the age-adjusted mortality for chronic obstructive pulmonary disease (COPD) has actually risen 71% over the past thirty years(2). Indeed, estimates predict that COPD will be the third leading cause of death and the fifth leading cause of disability worldwide by the year 2020(3,4). In order to improve these trends in the future, it is imperative that pharmacologic agents be developed that can halt or reverse the pathophysiologic changes that occur in this disease. Current guidelines for COPD management advocate the use of inhaled β 2 -agonists, inhaled anticholinergics and inhaled corticosteroids for symptomatic management(5). Long acting bronchodilators including the anti-cholinergic tiotropium, given once daily, and the β 2 -agonists salmeterol and formoterol given twice daily all improve lung function, quality of life and reduce the time to first exacerbation when compared to placebo(6-8). Likewise, several clinical trials have shown that inhaled steroids significantly reduce the rate of exacerbations in COPD(9,10). Importantly, a recent study demonstrated that combination therapy with salmeterol and fluticasone proprionate reduced Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply...

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“…The glucuronidation of EGCG and EGC were investigated using HLM and UTG expressed isozymes. EGCG was determined to be glucuronidated predominantly by UGT1A1, 1A8, and 1A9 [46]. Irinotecan is largely metabolized by UGT1A1 to 7-ethyl-10-hydroxycamptothecin glucuronide (SN-38G) [47].…”

Section: Uridine 5′-diphospho-glucuronosyltransferase Enzymementioning

confidence: 99%

Untitled

2017

Planta Med

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Glucuronides of Tea Catechins: Enzymology of Biosynthesis and Biological Activities

Cited by 199 publications

References 30 publications

Autoxidative quinone formation in vitro and metabolite formation in vivo from tea polyphenol (-)-epigallocatechin-3-gallate: Studied by real-time mass spectrometry combined with tandem mass ion mapping

Autoxidative quinone formation in vitro and metabolite formation in vivo from tea polyphenol (-)-epigallocatechin-3-gallate: Studied by real-time mass spectrometry combined with tandem mass ion mapping

The pharmokinetic limitations of antioxidant treatment for COPD

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