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Absorption and urinary excretion of procyanidin B2 [epicatechin-(4β-8)-epicatechin] in rats

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Abstract

We evaluated the bioavailability and plasma antioxidative activity after administration of procyanidin B2 [epicatechin-(4β-8)-epicatechin] in rats. After procyanidin B2 administration, procyanidin B2 is absorbed and excreted in urine, and a portion of the PB2 is degraded to (−)-epicatechin and to the metabolized conjugated and/or methylated (−)-epicatechin internally in the rat. Moreover, PB2 reduces the accumulation of lipid peroxide in plasma oxidized by copper ions.

Introduction

Procyanidins, the monomer catechins, and their oligomers, are widely distributed in plants, and are present in grape seeds [1], apples [2], and cacao beans [3]. Cacao beans (Theobroma cacao), used to produce chocolate and cocoa, are rich in polyphenols, such as (+)-catechin, (−)-epicatechin (EC), procyanidin B2 (PB2), procyanidin C1, cinnamtannin A2, and other oligomeric procyanidins [4].

Epidemiological studies have shown that red wine may reduce coronary heart disease mortality, the so-called “French Paradox” [5]. Moreover, according to other epidemiological data, there is a negative correlation between plant polyphenol consumption and coronary heart disease incidence [6]. In addition, it was reported that there is a negative correlation between catechin intake and coronary heart disease mortality [7].

Previous studies have shown various physiological and biological functions of procyanidins in terms of their antioxidative activity. In vitro studies have shown that procyanidins extracted from grape seeds, apple pomace, or pine bark have free radical scavenging activity [8], [9], [10], inhibit low-density lipoprotein oxidation induced by metal ions or radical generators [11], protect the membrane peroxidation and hemolysis in rat erythrocytes induced by UV-B [12], and reduce TNFα-induced vascular cell adhesion molecule-1 expression and T-cell adherence to human umbilical vein endothelial cells [13]. An in vivo study using rabbits has shown that proanthocyanidin or proanthocyanidin-rich extract from grape seeds increases antioxidative activity in plasma [14].

Several in vitro studies have reported that procyanidin from cocoa powder also may have various beneficial effects, such as protection of tyrosine nitration and dimerization induced by peroxinitrite [15], prevention of human low-density lipoprotein oxidation induced by radical generators [16], inducement of endothelium-dependent relaxation on rabbit aortic rings [17], and reduction of interleukin-1β expression of phytohemagglutinin-stimulated peripheral blood mononuclear cells [18]. Previously, in an ex vivo study, we have reported that cocoa powder administration reduced the production of plasma lipid peroxide oxidized by radical generators or copper ions in rats [19], [20], and that the daily intake of cocoa powder increases the resistance to oxidation of low-density lipoproteins induced by radical generators or copper ions in humans [21]. Also, in an in vivo study, the polyphenol-rich fraction extracted from cocoa powder showed the susceptibility of low-density lipoproteins to oxidation in hypercholesterolemic rabbits [22] and the inhibitory effect on the accumulation of calcium and phosphorus in the rat aorta or kidney [23].

Procyanidin monomer EC was detected in human plasma after intake of chocolate and cocoa [24], [25]. However, little is known about the absorption, metabolism, and excretion of procyanidin oligomers, including PB2. There have been few reports about in vivo absorption and metabolism of procyanidin oligomers in cocoa powder. Déprez et al. [26] reported that proanthocyanidins were degraded to low-molecular weight metabolites by human colonic microflora and that several metabolites were detected in vitro in anoxic conditions. It has been reported that procyanidin oligomers (trimer to hexamer) purified from cacao decomposed to the procyanidin monomer and dimer under acidic conditions that resemble the gastric environment in vitro [27]. Recently, Spencer et al. [28] showed that epicatechin and a small amount of nonmethylated and methylated procyanidin dimer were detected on the serosal side by perfusion of the small intestine with PB2 and procyanidin B5. These results suggest that procyanidin oligomers are utilized in the body. In this study in rats, we report on the bioavailability and plasma antioxidative activity after administration of PB2, one of the major polyphenol components of cocoa powder.

Section snippets

Materials and methods

The Animal Committee of Meiji Seika Health and Bioscience Laboratories approved this study. All animals received humane care under institutional guidelines.

Identification of PB2, EC, and 3′-O-methyl-EC by LC-MS

Figure 2 shows typical LC-MS chromatograms of urine obtained within 18 h after PB2 administration. At m/z 577 in the LC-MS analysis, a single peak was detected at 10 min in urine with sulfatase H-5 treatment after PB2 administration (Fig. 2C), which corresponds to the PB2 mass number. The peak showed the same retention time as the PB2 standard (Fig. 2A), thus identifying it as PB2. Molecular ion [M-H] peaks at m/z 289 and 303 were detected at 11 min and 14 min in urine with sulfatase H-5

Discussion

PB2 is a major component of the polyphenol fraction in cocoa powder [4]. Previously, it has been reported that procyanidins containing PB2 might have various beneficial functions that affect human health, such as: radical scavenging activity [32], antitumor-promoting activity [33], antiatherosclerotic activity [14], anti-inflammatory activity [34], antielastase activity [35], antihypertensive activity [36] in vitro, ex vivo, and in vivo. These results suggest that some procyanidin forms from

Acknowledgements

We are grateful to M. Taneda (Tokyo R&D Center, Hitec Co. Ltd, Tokyo, Japan) and Y. Muto for their technical support in this study.

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