Difference in Plasma Metabolite Concentration after Ingestion of Lemon Flavonoids and Their Aglycones in Humans

Abstract

SummaryThe concentrations of metabolites in human plasma after ingestion of flavanone glycosides (FG) and their aglycones (FA) in lemon were examined. FG consisting abundantly of eriocitrin were prepared from lemon peel and FA consisting abundantly of eriodictyol were prepared from FG by treatment with ␤-glucosidase. Eriodictyol, homoeriodictyol, and hesperetin in plasma up to 4 h after ingestion of FG with water or FA with water by subjects were not detected in plasma of non-enzyme treatment but in plasma after treatment with ␤-glucronidase and sulfatase. Metabolites in plasma after ingestion of FG and FA in humans were shown to exist as the glucuro-and/or sulfo-conjugates of eriodictyol, homoeriodictyol, and hesperetin. After ingestion of FA, the concentration of metabolites in plasma exhibited a high maximum peak at 1 h. The AUC (area under the blood concentration time curve) level of metabolites of FA was higher than that of FG. FA were suggested to be absorbed faster and in higher amounts than FG. The AUC of metabolites in subject plasma after ingestion of FG with flavonoid-depleted lemon juice was shown to change to a low level in comparison with that of FG with water. The maximum concentration peak of metabolites in plasma was faster at 0.5 h than FA with water but the AUC level was similar to FA with water, when subjects ingested FA with vodka (40% ethanol). The absorption hour of FG and FA was shown to be affected by the co-existing solution. Key Words lemon flavonoid, eriocitrin, plasma, human, ingestion Epidemiological studies indicate a protective relationship between the consumption of citrus fruits or juice and the risk of ischemic stroke and lung cancer (1, 2). Some fundamental studies support a protective effect provided by flavonoid consumption in these diseases (3-6). Citrus fruits contain various kinds of flavonoids such as flavanone glycoside, flavone glycoside, and polymethoxyflavone (3, 4). Flavonoids in lemon fruit (Citrus limon BURM. f.) have been reported to be such flavanone glycosides as eriocitrin (eriodictyol 7-O-␤-rutinoside) and hesperidin (hesperetin 7-O-␤-rutinoside) and such flavone glycosides as diosmin (diosmetin 7-O-␤-rutinoside) and 6,8 C-diglucosyldiosmetin (7-10). Eriocitrin has been reported to be the most abundant flavonoid in lemon fruit and to have the highest antioxidative activity of the flavonoids in citrus fruits in vitro (9,11). It was also shown to have a suppressive effect for oxidative stress in the liver of streptozotocin-induced diabetic rats (12) or exercise-induced rats (13).For the study of functional compounds such as flavonoids in foods, it is important to determine how the compounds in food are metabolized and absorbed in vivo and how the metabolites function in a living system. There have been several human studies that have investigated the metabolism and absorption of flavonoids (14), such as anthocyanin (15, 16), flavonol (17, 18), isoflavone (19), and flavanone (20-22). As for eriocitrin, it was reported for metabolites by human intestinal bacteri...

Preparation of a Lemon Flavonoid Aglycone and its Suppressive Effect on the Susceptibility of LDL to Oxidation Following Human Ingestion

“…1 (Kawai et al, 1999;Miyake et al, 2007). LF, which is prepared from lemon peel and predominantly contains eriocitrin, has been reported to have low bioavailability when orally ingested by humans (Miyake et al, 2006b), although it exhibited bioactivities such as a suppressive effect on oxidative stress in experimental animals (Miyake et al, 1998(Miyake et al, , 2006a). An oral intake test in rats has shown that eriocitrin is absorbed after it is converted to eriodictyol of an aglycone by intestinal bacteria (Miyake et al, 2000).…”

“…Change of flavonoids in LF by enzyme treatment LF was prepared from lemon peel using the reported method (Miyake et al, 2006b). The solution (5 mL) prepared with 10 mg/mL of LF, 1 mg/mL of each enzyme (cellulase, hesperidinase, naringinase, pectinase) and 50 mM of sodium acetate-HCl buffer solution (pH 3.5) at final concentration was incubated at 37℃ for 3 h. The reaction was carried out at pH 3.5, because enzymes have been used in citrus juice of pH 3-4 in citrus factories.…”

“…Determination of flavonoids in plasma after ingestion of LFA Eriodictyol, hesperetin, and homoeriodictyol in plasma were analyzed by the previously described method (Miyake et al, 2006b). For the determination of free type, the plasma sample (0.5 mL) was applied to a DISPO COLUMN C18H050 (Toyo Roshi Ltd., Tokyo, Japan) and the methanol elute solution was evaporated to dryness.…”

“…The mixtures were applied to a DISPO COLUMN C18H050, and the methanol elute solution was evaporated to dryness. The dried samples were dissolved in 50 µL of methanol, and eriodictyol, hesperetin, and homoeriodictyol in the solution were analyzed by HPLC as previously described (Miyake et al, 2006b). The concentration values of flavonoids in the plasma were represented as mean ± SE (µg/ mL of plasma, n=10).…”

“…However, LF has been shown to have low bioavailability in tests of single-dose oral ingestion in humans. Meanwhile, a lemon flavonoid aglycone (LFA), which is prepared from LF by β-glucosidase for regent, was shown to have higher bioavailability than LF (Miyake et al, 2006b). In this study, we prepared LFA from LF, using various enzymes that are commonly used in the citrus industry for citrus processing, such as cellulase, naringinase, hesperidinase, and pectinase.…”