Bioavailability of the flavanone naringenin and its glycosides in rats

Abstract

Naringenin, the predominant flavanone in grapefruit, mainly occurs as glycosides such as naringenin-7- rhamnoglucoside or naringenin-7-glucoside. This study compared kinetics of absorption of naringenin and its glycosides in rats either after a single flavanone-containing meal or after adaptation to a diet for 14 days. Regardless of the diet, circulating metabolites were glucurono- and sulfoconjugated derivatives of naringenin. The kinetics of absorption of naringenin and naringenin-7-glucoside were similar, whereas naringenin-7-rhamnoglucoside exhibited a delay in its intestinal absorption, resulting in decreased bioavailability. After naringenin-7-glucoside feeding, no glucoside was found in the cecum. However, after feeding naringenin-7-rhamnoglucoside, some naringenin-7-rhamnoglucoside accumulated in cecum before being hydrolyzed by intestinal microflora. Adaptation to flavanone diets did not induce accumulation of plasma naringenin. Moreover, flavanone cecal content markedly decreased after adaptation, and almost no naringenin-7-rhamnoglucoside was recovered after naringenin-7-rhamnoglucoside feeding, suggesting that an adaptation of cecal microflora had occurred. Overall, these data indicate that flavanones are efficiently absorbed after feeding to rats and that their bioavailability is related to their glycosidic moiety.

Bioavailability in humans of the flavanones hesperidin and narirutin after the ingestion of two doses of orange juice

“…In the present study, hesperidin metabolites recovered in plasma were identified as glucuronides of hesperetin, among which a low part was also sulphated. To our knowledge, the nature of the metabolites of flavanones in human plasma has never been described in the literature, but our results are in agreement with the findings of animal studies (Peng et al, 1998;Choudhury et al, 1999;Felgines et al, 2000). Besides, the presence of glucuronides of flavanones has been reported in human urine (Fuhr & Kummert, 1995;Ameer et al, 1996;Lee & Reidenberg, 1998).…”

“…In rats, rutinosides and neohesperidosides are not deglycosylated nor absorbed in the small intestine, but are converted into aglycones by the intestinal bacteria, and then absorbed in the caecum (Felgines et al, 2000;Griffiths & Barrow, 1972; Figure 3 Individual plasma concentration curves for hesperetin after ingestion of 1 l of orange juice. Concentration of aglycones were determined by HPLC with Coularray detection, after hydrolysis by a b-glucuronidase-sulphatase.…”

“…A few studies have reported antioxidative or anti-inflammatory activity of flavonoid conjugates (Manach et al, 1998;Hiermann et al, 1998;Day et al, 2000;Moon et al, 2001). The intestinal microflora, besides the deglycosylation of narirutin and hesperidin, has also the capacity to degrade the aglycones into phenolic acids such as p-hydroxyphenylpropionic, p-coumaric, and p-hydroxybenzoic acids (Booth et al, 1958;Scheline, 1991;Felgines et al, 2000). It is quite possible that these phenolic acids were also present in human urine or plasma, but they were not detectable in our chromatographic conditions.…”

“…Animal studies have shown that hesperidin and naringin are not absorbed as such but are hydrolysed into aglycones which are recovered in plasma, urine and bile as glucuronides and sulpho-glucuronides (Booth et al, 1958;Hackett et al, 1979;Felgines et al, 2000). Until recently, the few human studies available reported data on the urinary excretion of flavanones after the intake of pure compounds or grapefruit juice (Ameer et al, 1996;Fuhr & Kummert, 1995;Lee & Reidenberg, 1998;Ishii et al, 2000).…”

Absorption and pharmacokinetics of grapefruit flavanones in beagles

“…The identification and measurement of flavonoid conjugates are key prerequisites to understand the role of these compounds, since these are the forms that will reach tissues and exert their biological effect. Previous studies of naringin (naringenin-7-O-rhamnoglucoside) metabolism have suggested that sugar moiety cleavage, by gut microflora a-rhamonosidases, is the first step of this pathway, leading to the formation of naringenin, which undergoes rapid glucuronidation or sulphatation in the intestine or liver (Fuhr & Kummert, 1995;Felgines et al 2000;Scalbert & Williamson, 2000). Most studies have applied enzymatic hydrolysis with sulphatase and glucuronidase in order to identify the aglycone naringenin, and thus the individual metabolic profiles are lost during the hydrolysis procedure (Fuhr & Kummert, 1995;Ishii et al 1996Ishii et al , 1997Hollman et al 1999;Erlund et al 2001;Bugianesi et al 2002;Manach et al 2003;Zhang & Brodbelt, 2004).…”