Pharmacokinetics of selected chiral flavonoids: hesperetin, naringenin and eriodictyol in rats and their content in fruit juices

Abstract

The majority of pharmacokinetic studies of individual flavonoids or after ingestion of foodstuffs have overlooked the chirality of some of these xenobiotics. In order to characterize for the first time the stereoselective pharmacokinetics of three flavonoids, hesperetin, naringenin and eriodictyol were intravenously administered (20 mg/kg) to male Sprague-Dawley rats, and their stereospecific content was assessed in various fruit juices. Concentrations in serum, urine and fruit juices were characterized via HPLC and verified by LC/MS. Short half-lives (3-7 h) in serum were observed, while a better estimation of half-life (12-48 h) and the other pharmacokinetic parameters was observed using urinary data. The three flavonoids are predominantly excreted via non-renal routes (fe values of 3-7%), and undergo rapid and extensive phase II metabolism. The (2S)-epimers of the flavonoid glycosides and the S(-)-enantiomers of the aglycones were predominant and in some instances the organic fruit juices had higher concentrations than the conventional fruit juices. This study reports for the first time the stereospecific pharmacokinetics of three chiral flavonoids and their stereospecific content in fruit juices. It also reports for the first time the stereospecific pharmacokinetics of flavonoids employing urine as a more reliable biological matrix.

Analysis of hesperetin enantiomers in human urine after ingestion of blood orange juice by using nano-liquid chromatography

“…The confirmation of elution order was done analyzing orange juice and urine sample after ingestion of juice. The results were compared to those reported in literature where these samples contained stereochemically enriched S(−)hesperidin or S(−)hesperetin [3].…”

“…Despite several successful methods, including micellar electrokinetic chromatography (MEKC) [14], capillary electrophoresis (CE) [15] and high-performance liquid chromatography (HPLC) [16,17], have been used to enantioseparate hesperetin, only few papers dealing with the enantioselective identification and quantification of HT in biological fluids were reported [3,18]. Yáñez et al developed a HPLC method for the separation of these chiral compounds using a commercial cellulose based silica column [3].…”

“…Yáñez et al developed a HPLC method for the separation of these chiral compounds using a commercial cellulose based silica column [3]. Recently, racemic hesperetin was resolved in its enantiomers by our group using nano-liquid chromatography (nano-LC) by means of a phenyl-carbamate-propyl-␤-cyclodextrin stationary phase [19].…”

The flavonoid composition of flavedo and juice from the pummelo cultivar (Citrus grandis (L.) Osbeck) and the grapefruit cultivar (Citrus paradisi) from China

“…Citrus fruit contain large amounts of polyphenolics, especially flavonoids, which have significant biological activity (Abeysinghe et al, 2007;Bocco, Cuvelier, Richard, & Berset, 1998;Di Donna et al, 2009;Tripoli, La Guardia, Giammanco, Di Majo, & Giammanco, 2007). The antioxidant activity of several citrus fruits (sweet orange, lemon, grapefruit, bergamot, lime and mandarin) has been investigated using either the fruit itself or its extracts (Abeysinghe et al, 2007;Bocco et al, 1998;Di Majo et al, 2005;Yáñez et al, 2008). The identification and/or quantification of flavonoids has been mainly carried out on lemon, orange, and grapefruit species and cultivars (Barreca, Bellocco, Caristi, Leuzzi, & Gattuso, 2010, 2011Caristi et al, 2003;Gattuso et al, 2006;Kanes, Tisserat, Berhow, & Vandercook, 1993;Kawaii, Tomono, Katase, Ogawa, & Yano, 1999;Peterson et al, 2006;Tripoli et al, 2007).…”

Enantioseparation of Physiologically Active Some Flavonoids by Liquid Chromatography-Electrospray-Tandem Mass Spectrometry Based on Noncovalent Interactions with β-Cyclodextrin

“…Recently, interests in the potential therapeutic uses, plant physiologies, and health benefits of chiral flavanones have increased. [20][21][22] Therefore stereospecific assay methods for effective separation of chiral flavanones are necessarily needed. In this study, flavanone (2,3-dihydroflavone and naringenin), flavanone glycosides (naringin), and catechin were tested.…”