Identification and Antioxidant Activity of Flavonoid Metabolites in Plasma and Urine of Eriocitrin-Treated Rats

Abstract

Eriocitrin, a flavonoid glycoside present in lemon fruit, is metabolized in vivo to a series of eriodictyol, methylated eriodictyol, 3,4-dihydroxyhydrocinnamic acid, and their conjugates. Plasma antioxidant activity increased following oral administration of aqueous eriocitrin solutions to rats. Eriocitrin metabolites were found in plasma and renal excreted urine through HPLC and LC-MS analyses. Eriocitrin was not detected in plasma and urine, but eriodictyol, homoeriodictyol, and hesperetin in their conjugated forms were detected in plasma of 4.0 h following administration of eriocitrin. In urine for 24 h, both nonconjugates and conjugates of these metabolites were detected. 3,4-Dihydroxyhydrocinnamic acid, which is metabolized from eriodictyol by intestinal bacteria, was detected in slight amounts with each form in 4.0-h plasma and 24-h urine. Eriocitrin was suggested to be metabolized by intestinal bacteria, and then eriodictyol and 3,4-dihydroxyhydrocinnamic of its metabolite were absorbed. Following administration of eriocitrin, plasma exhibited an elevated resistance effect to lipid peroxidation. Eriocitrin metabolites functioning as antioxidant agents are discussed.

Isolation of eriocitrin (eriodictyol 7‐O‐rutinoside) as an arachidonate lipoxygenase inhibitor from Lumie fruit (Citrus lumia) and its distribution in Citrus species

“…Eriocitrin is converted to eriodictyol and 3,4-dihydroxyhydrocinnamic acid (3,4-DHCA) by intestinal bacteria, and conjugated forms of eriodictyol, homoeriodictyol and hesperetin, and free 3,4-DHCA were detected in rat plasma. 28 Shimoi et al 29 have suggested that deglucuronidation occurs at focal sites during inflammation. Thus eriodictyol in a free form possibly plays an important role in the inhibition of LOX activity during inflammation.…”

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

“…Moreover, the resistance effect of oxidation in whole plasma after ingestion of LA in rat has been reported (Miyake et al, 2000). The resistance effect of LDL oxidation in plasma has been associated with prevention of cardiovascular disease (Goldstein et al, 1979;Sies et al, 2005).…”

“…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). LFA containing 14.7% eriodictyol has been reported to be prepared from LF by β-glucosidase (G4511, from almonds, Sigma Chemical Co., USA) as a reagent, and has been shown to have higher bioavailability than LF in oral ingestion tests in humans (Sakurai, et al, 2003;Miyake et al, 2006b).…”

“…1 (Miyake et al, 2000;Miyake et al, 2006). HPLC was employed in an attempt to detect the flavonoids in plasma after the oral ingestion of LFA by humans.…”

“…The resistance effect of LDL oxidation was presumed to be related to metabolites of LFA in plasma after the ingestion of LFA, although research will have to be conducted for relation with the effect. Eriodictyol had been suggested to be metabolized by methylation and conjugation with glucuronic acid and/or sulfonic acid after it was absorbed from the intestine (Miyake et al, 2000;. Hesperetin has been reported to exhibit low activity in the assay using measuring of LDL lag time in vitro in comparison with eriodictyol (Miyake et al, 1997).…”