Metabolites of epicatechin

Unno T, Tamemoto K, Yayabe F, Kakuda T. 2003. Urinary excretion of 5-(3, 4 -d i hydroxypheny 1 )-gainma-valerolactone, a ring-fission metabolite of (—)-epicatechin, in rats and its in vitro antioxidant activity. J Agric Food Chem 51 6893-6898. 

Figure 4 The structures of the main small Intestinal metabolites of epicatechin produced in the isolated rat small intestine perfusion model. (A) 3 -0-methyl epicatechin (B) 4 -0-methyl epicatechin (C) 3 -0-methyl epicatechin-5-glucuronide (D) epicatechin-5-glucuronide (E) epicatechin-7-glucuronide.

Terao J. Dietary flavonoids as antioxidants in vivo conjugated metabolites of (-)-epicatechin and quercetin participate in antioxidative defense in blood plasma. J Med Invest 1999 46 159-168. 

Intestinal excretion is an important mechanism in the elimination of flavonoid conjugates [82-84]. This is likely mediated by the multidrug resistance-associated protein (MRP) pumps. MRPs actively export conjugated metabolites out of the small intestine back into the intestinal lumen and so prevent or reduce systemic circulation [85]. An experiment using cultured Caco-2 cells showed that two metabolites of epicatechin were excreted on the apical side of the cells. Their elimination has been attributed to MRP-2, as efflux was significantly reduced by a competitive MRP-2 inhibitor [86]. Conversely, intestinal perfusion experiments with catechin indicate that catechin metabolites are not substrates for these transport proteins [49]. 

Absorption of (-)-epicatechin from chocolate has been studied by different authors [104-106]. Baba et al [104] found maximum levels of total EC metabolites in plasma after 2 h of chocolate or cocoa intake. Sulfate, glucuronide and sulfoglucuronide conjugates of non-methylated EC were the main metabolites present rather than methylated forms. In urine samples, excretion of total EC metabolites within 24 h was about 30% of total EC intake after chocolate and 25 % after cocoa consumption. 

LC/ESI-MS analyses were applied to determine urinary glucuronidated and sulfated tea catechins after the administration of green tea to humans, mouse and rats [109]. The major conjugates were identified as monoglucuronides and monosulfates of EGC and EC. Besides these metabolites, also G-methyl-EGC-G-glucuronides, O-sulfates and O-methyl-EC-O-sulfates in human urine were detected. Furthermore, the ring-fission metabolites of EGC and (-)-epicatechin, 5-(3 ,4 ,5 -trihydroxyphenyl)-y-valerolactone and 5-(3 ,4 -dihydroxyphenyl)- valerolactone respectively, have been detected in the monoglucuronide and monosulfate forms. 

Piskula MK, Terao J. 1998. Accumulation of (—)-epicatechin metabolites in rat plasma after oral administration and distribution of conjugation enzymes in rat tissues. J Nutr 128 1172-1178. 

Inflammation is now recognized as a key process in atherogenesis [Libby, 2002]. The potential for dietary flavonoids to inhibit inflammatory activities is of particular interest. A potential anti-inflammatory feature of the flavonoids is the ability to inhibit the biosynthesis of eicosanoids. Selected phenolic acids and some flavonoids have been shown to inhibit both cyclooxygenase (COX) and 5-lipoxygenase (5-LO) pathways [Nijveldt et al., 2001 Takano-Ishikawa et al., 2006], Epicatechin and related flavonoids have been shown to inhibit the synthesis of pro-inflammatory cytokines in vitro [Sanbongi et al., 1997], and plasma metabolites of catechin and quercetin inhibit the adhesion of monocytes to cultured endothelial cells [Koga and Meydani, 2001]. Silymarin has been shown to inhibit the production of inflammatory cytokines, such as interleukin-1, interferon-, and tumor necrosis factor-a (TNFa), from macrophages and T-cells [Matsuda et al., 2005], Some flavonoids can inhibit neutrophil... 

Among the metabolites circulating in human blood plasma after intake of (—)-epicatechin, the major one is the glucuronide [Natsume et ah, 2003]. We suggest that the epicatechin glucuronide serves as transport metabolite, taken up into the cells and after deglucuronidation delivering the flavanol... 

Okushio K, Suzuki M, Matsumoto N, Nanjo F, Hara Y. 1999. Identification of (—)-epicatechin metabolites and their metabolic fate in the rat. Drug Metab Dispos 27 309-316. 

Fig. 13.6 Structures of EC metabolites in human plasma after oral ingestion of (-)-epicatechin (data from...

The specific forms of epicatechin metabolites as well as methylated forms were measured after chocolate and cocoa consumption. This study reported much higher maximal plasma levels (4.8 pM) than all other studies as well as a 25-30% recovery rate in mine. Epicatechin was present as a mixed sulfate/ glucuronide, a sulfate conjugate, and a glucuronide conjugate. Methylated epicatechin accounted for up to 40% of the total amount of metabolites and was present as a sulfate or a mixed sulfate/glucuronide conjugate [59]. 

Further proanthocyanidin metabolites that occur sporadically in the plant kingdom are the 3-O-gallates. Until recently, they were known only as acylated derivates of epicatechin or epigallocatechin, but several instances are now known of acylation of proanthocyanidin units as well (Sect. 7.7.4.1). 

Harada, M., Kan, Y., Naoki, H., Fukui, Y., Kageyama, N., Nakai, M., Miki, W., and Kiso, Y, Identification of the major antioxidative metabolites in biological fluids of the rat with ingested (+)-catechin and (-)-epicatechin. Biosci. Biotechnol. Biochem., 63, 973, 1999. 

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