Biology Reference
In-Depth Information
plasma, punicalagin was detected at concentrations of
ca
. 30 μg/mL
(0.028 μM). The absorption of intact punicalagin in rats and its detection
in plasma is particularly remarkable, for punicalagin (Mw = 1084) is one
of the largest polyphenols that has been reported to be absorbed (Cerdá
et al
., 2003a, Manach
et al.
, 2005). Glucuronides and methyl ether
conjugates of EA were also detected in this study. In urine, the main
metabolites observed were the mono-, di- and trihydroxy-6
H
-dibenzo-
[b,d]-pyran-6-one derivatives, both as aglycones and glucuronide
conjugates (Cerdá
et al
., 2003a). Only 3 to 6% of the ingested
punicalagin was detected under its native form or as derived metabolites
in urine and faeces, suggesting that the majority of this ET had to be
converted to undetectable metabolites or accumulated in tissues. Traces
of punicalagin metabolites were further detected in liver and kidney, but
punicalagin, EA or other derived metabolites were not found in lung,
brain or heart (Cerdá
et al
., 2003a and 2003b).
In this study, in addition to the very small quantities of punicalagin,
the pomegranate ET metabolites detected in plasma included trihydroxy-
6
H
-dibenzopyran 6-one diglucuronide and dihydroxy-6
H
-dibenzopyran
6-one glucuronide, gallagic acid, dimethylated ellagic acid glucuronide,
dimethylated ellagic acid glucuronide methyl ester and very small
amounts of EA. As EA has two
ortho
-dihydroxyphenyl units, it can be
expected that, in the liver,
via
COMT (catechol
O
-methyl transferase)
activity, one methyl ether group can be introduced per dihydroxyphenyl
unit. These metabolites show a UV spectrum nearly identical to that of
free EA, and were further conjugated with glucuronic acid to increase
water solubility and to facilitate their excretion (Cerdá
et al.
, 2003a).
7.5.4 Humans
In humans, two main types of experiments have been carried out: i)
pharmacokinetic studies, in which the absorption of pomegranate
polyphenols has been evaluated during several hours following intake; ii)
bioavailability and metabolism studies, in which the metabolites present
in plasma and urine have been evaluated for long periods of time. In a
pharmacokinetic study carried out at the University of California, Los
