Epicatechin and Catechin are O-Methylated and Glucuronidated in the Small Intestine

“…Glucuronidation and sulfation metabolize polyphenols into very hydrophilic conjugates whereas methylation produces metabolites that have essentially same if not slightly more lipophilic metabolites. Regardless if methylation occurs, the methylated products are usually conjugated subsequently into glucuronides and sulfates, as long as there is a functional group available for conjugation into more hydrophilic metabolites [74,75]. Therefore, conjugation enzymes that catalyzed the formation of these hydrophilic metabolites significantly impact the bioavailability of polyphenols.…”

Section: Conjugation Enzymesmentioning

confidence: 99%

Natural polyphenol disposition via coupled metabolic pathways

Liu¹,

Hu²

2007

Expert Opinion on Drug Metabolism & Toxicology

126

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A major challenge associated with the development of chemopreventive polyphenols is the lack of bioavailability in vivo, which are primarily the result of coupled metabolic activities of conjugating enzymes and efflux transporters. These coupling processes are present in most of tissues and organs in mammals and are efficient for the purposes of drug metabolism, elimination and detoxification. Therefore, it was expected that these coupling processes represent a significant barrier to the oral bioavailabilities of polyphenols. In various studies of this coupling process, it was identified that various conjugating enzymes such as UGT and SULT are capable of producing very hydrophilic metabolites of polyphenols, which cannot diffuse out of the cells and needs the action of efflux transporters to pump them out of the cells. Additional studies have shown that efflux transporters such as MRP2, BCRP and OAT appear to serve as the gate keeper when there is an excess capacity to metabolize the compounds. These efflux transporters may also act as the facilitator of metabolism when there is a product/metabolite inhibition. For polyphenols, these coupled processes enable a duo recycling scheme of enteric and enterohepatic recycling, which allows the polyphenols to be reabsorbed and results in longer than expected apparent plasma half-lives for these compounds and their conjugates. Since the vast majority of polyphenols in plasma are hydrophilic conjugates, more research is needed to determine if the metabolites are active or reactive, which will help explain their mechanism of actions.

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“…Studies using the isolated rat small intestine have also established that flavonoids are substrates for ␤-glucosidases [184,192], UDP-glucuronyl transferases [110,111,192], and catechol-O-methyl transferases leading to methylation of odihydroxy catechol structures and that the major metabolites of epicatechin on transfer across the small intestine include O-methylated and glucuronidated forms [110] (Fig. 4).…”

Section: Metabolism and Distribution Of Flavonoids In Mammals And Thementioning

confidence: 99%

MAPK signaling in neurodegeneration: influences of flavonoids and of nitric oxide

Schroeter

Boyd

Spencer

et al. 2002

Neurobiology of Aging

308

178

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Oxidative and nitrosative stress is increasingly associated with the pathology of neurodegeneration and aging. The molecular mechanisms underlying oxidative/nitrosative stress-induced neuronal damage are emerging and appear to involve a mode of death in which mitogen-activated protein kinase (MAPK) signaling pathways are strongly implicated. Thus, attention is turning towards the modulation of intracellular signaling as a therapeutic approach against neurodegeneration. Both endogenous and dietary agents have been suggested as potent modulators of intracellular signal transduction, e.g. nitric oxide and flavonoids, respectively. This review addresses recent findings on the biological effects of flavonoids and nitric oxide in neurodegeneration and aims to elucidate the rationale for their prospective use as modulators of cellular signal transduction. © 2002 Elsevier Science Inc. All rights reserved.Keywords: Apoptosis; Oxidative stress; Neuron; Flavonoids; MAP kinase; JNK; ERK; Epicatechin; Nitric oxide; Mitochondria; Redox status; Polyphenols Abbreviations: AKT, serine/threonine kinase (also known as protein kinase B); AP-1, activator protein-1; Apaf-1, apoptosis protease activating factor-1; ASK1, apoptosis signal-regulating kinase-1; Bad, Bcl-2/BclX Lassociated death promoting protein; Bax, pro-apoptotic protein of the Bcl-2 family; Bcl-2, B-cell lymphoma 2: protein with anti-apoptotic properties; BclX L , long form of Bclx: anti-apoptotic protein of the Bcl-2 family; Caspase, cysteinyl aspartic acid-protease; c-Jun, mammalian equivalent of Jun: part of the AP-1 transcription complex; CREB, cAMP response element binding protein; DIABLO/smac, mitochondria-related pro-apoptotic protein: inhibits XIAP; ERK1/2, extracellular signal-related kinase; Fas, CD95: member of the TNF receptor family; GSHST, glutathione Stransferase; JNK, c-Jun amino-terminal kinase; MAPK, mitogen-activated protein kinase; MAPKK, MAPK kinase; MAPKKK, MAPKK kinase; MEK1/2, ERK1/2-specific MAPKK; MKK4/7, JNK-specific MAPKK; MSK1, mitogen-and stress-activated kinase-1; NF-B, nuclear factor of immunoglobulin k locus in B-cells; ONOO − , peroxynitrite anion; p53, pro-apoptotic tumor suppressor gene product; PI3-kinase, phosphoinositol 3-kinase; Ras, small G-protein; RNS, reactive nitrogen species; ROS, reactive oxygen species; RSK, pp90 ribosomal S6 kinase; SAPK, stressactivated protein kinase; XIAP, X-linked inhibitor of apoptosis: inhibits the activation of caspase-9

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Epicatechin and Catechin are O-Methylated and Glucuronidated in the Small Intestine

Cited by 185 publications

References 25 publications

Free radical scavenging, <i>in vivo</i> antioxidant and hepatoprotective activity of folk medicine <i>Trichodesma sedgwickianum</i>

Free radical scavenging, <i>in vivo</i> antioxidant and hepatoprotective activity of folk medicine <i>Trichodesma sedgwickianum</i>

Natural polyphenol disposition via coupled metabolic pathways

MAPK signaling in neurodegeneration: influences of flavonoids and of nitric oxide

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