Chapter 6
Bioavailability and Metabolic Fate of Anthocyanins Takashi Ichiyanagi
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Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, 265-1 Higashijima, Niigata 956-8603, Japan In the present study, bioavailability and metabolic fate of naturally occurring anthocyanins with different structures were precisely examined for the understanding of their in vivo functionalities. Attached sugar types were the major modulating factor for the absorption of mono-glycosylated anthocyanins carrying the same aglycone. Bioavailability of bilberry anthocyanins (anthocyanin mixture) was 0.93%. It was further revealed that acylated anthocyanin such as nasunin showed better uptake than non-acylated analogues carrying the same aglycone. Interestingly, the pattern of anthocyanins distributed in tissues was completely different from that of administered anthocyanin mixture and O-methyl analogues were the major anthocyanins in liver and kidney, indicating these anthocyanins will play a critical role in tissues. From the precise study on the metabolism of six types of purified anthocyanins, it was clarified that the general metabolic path of anthocyanin in rats was 0-methylation of Β ring and glucuronidation of both anthocyanidin and anthocyanin (extended glucuronidation).
Anthocyanins are reddish pigment widely distributed in colored fruits (1-4) and vegetables (5-9). Glycoside or acyl glycoside of anthocyanidin is naturally occurring forms of anthocyanin. Acylated anthocyanins are further classified into two groups depending on the types of attached acyl moiety. They are aliphatic and aromatic types. Recently, numerous studies on functionality of anthocyanins such as improvement of vision (10,11), α-glucosidase inhibition (12,13) and antioxidant activity (14) have been reported. Anticancer activity of anthocyanins has also been reported both in vivo and in vitro (15). However, for 48
© 2008 American Chemical Society
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Anthocyanin Delphinidin 3-0-/?-D-galactopyranoside Delphinidin 3-0-/^D-glucopyranoslde Delpliinidiii 3-0 - a -L-ar abinopyi anoside Cyanidin 3-0 -/J-D-galactopyr anoside CV aniclin 3-0 -/?-i>-glucopyr anoside Cyanicttn 3-O-a -L-arabinopyranoside Petimidin 3-0 -/?-D-galactopyr anoside Petunicttn 3- 0-/?-D-ghicopyr anoside Petimidin 3-O-a -L-arabinopyranoside Peonidin 3- 0 - /?-D-galactopyr anoside Peonidin 3-0-/?-o-glucopyr anoside Peonidin 3-O-tfL-arabinopyr anoside Malvidin 3-0-/?-D-galactopyr anoside Mahidin 3-0 -/?-D-ghicopyr anoside Malvidin 3-O-a -L-arabinopyranoside
trans-nasunin
cyanidin 3-0-/?-D-glucopyranoside mono-malonvlate
H H H H H H H H H CH CH CH CH CH CH
R* OH OH OH H H H CH
R galactopyranose ghicopyr anose arabinopyr anose galactopyranose glucopyranose ai abinopyr anose galactopyranose
Peak 1 2 4 3 5
CH CH
glucopyranose ai abinopy ranose
8 10
galactopyranose glucopyranose
9 11 13 12 14 15
3
3
3
3
3
3
3
H H H CH CH CH
3
3
3
3
3
3
ai abinopyI anose galactopyranose ghicopyr anose ai abinopyl anose
7
6
cis-nasunin
cyanidin 3-0-/?-i>-glucopyranoside di-malonvlate
Figure 1. Structure of anthocyanins studied in the present report.
Shibamoto et al.; Functional Food and Health ACS Symposium Series; American Chemical Society: Washington, DC, 2008.
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50 further discussion of in vivo functionality of anthocyanins, it is critical to know the physiological uptake and distribution of each anthocyanin in plasma and tissues together with their metabolic fate. Recently, we examined quantitative and systematic comparison of absorption and bioavailability of anthocyanins using bilberry (a wild type blueberry) extract because it contains fifteen types of anthocyanins comprised of five types of anthocyanidin (anthocyanin aglycone) and three types of attached sugar (Figure 1) (76). Further, metabolism of anthocyanins has been clarified using purified anthocyanins (six types of nonacylated and four types of acylated anthocyanins (Figure 1) by high sensitive semi-micro high performance liquid chromatography (HPLC), tandem-time of flight mass spectrometry (TOF MS) and nuclear magnetic resonance (NMR) techniques (17-21). In the present report, absorption and metabolism of anthocyanins are summarized together with their tissue distribution and discussed the relationship between the structural diversity and the biological behavior of anthocyanins in vivo.
Results and Discussion Absorption and Bioavailability of Anthocyanins in Rats Figure 2A showed typical HPLC chromatogram of anthocyanins in bilberry extract. Fifteen anthocyanins were detectable in bilberry extract together with minor two anthocyanidins (aglycone). Figure 2B showed HPLC chromatogram of rat blood plasma after 15 min of oral administration of bilberry extract (400 mg/kg body weight; 153.2 mg/kg as anthocyanins). Fourteen anthocyanins except peonidin 3-O-a-L-arabinopyranoside were detectable in rat blood plasma after oral administration of bilberry extract. The difference of anthocyanin profile on HPLC chromatogram in plasma from that of original bilberry extract indicates that absorption, excretion, and probably the metabolic fate are different among the anthocyanins. The pharmacokinetic parameters of each anthocyanin were summarized in Table I together with orally administered dose (mmol/kg) of each anthocyanin in bilberry extract (400 mg/kg body weight). The maximum plasma level of anthocyanins in the plasma was as follows; galactopyranoside > glucopyranoside > arabinopyranosides in any anthocyanins with the same aglycone except malvidin (Table I). When the bioavailability of anthocyanins carrying the same aglycone was compared, galactopyranoside tended to show a higher value than glucopyranoside. On the other hand, when the bioavailability of anthocyanins with the same sugar moiety was compared, peonidin tended to show the highest value. The bioavailability ofanthocyanin as mixture was 0.93%. These results indicated that both aglycone and attached sugar moiety are the modulator for gastrointestinal absorption of anthocyanins.
Shibamoto et al.; Functional Food and Health ACS Symposium Series; American Chemical Society: Washington, DC, 2008.
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51
Figure 2. HPLC chromatogram of bilberry extract (Bilberon 25). A: Bilbery extract, B: Rat blood plasma after 15 min of oral administration.
Shibamoto et al.; Functional Food and Health ACS Symposium Series; American Chemical Society: Washington, DC, 2008.
Shibamoto et al.; Functional Food and Health ACS Symposium Series; American Chemical Society: Washington, DC, 2008.
Peak 1 2 4 3 5 7 6 8 10 9 11 13 12 14 15 Anthocyanin as mixture
-
2.827 ± 3.069 ± 2.260 ± 3.571 ±
0.006 0.009 0.002 0.131
0.039 ± 0.075 ± 0.010 ± i 207 ±
-
4.664 ± 3.830 ± 2.677 ± 4.994 ± 3.828 ± 2.522 ± 4.338 ± 3.055 ± 1.735 ± 7.288 ± 2.903 ± 0.454 0.385 0.358 0.613
0.575 0.510 0.253 0.625 0.592 0.282 1.031 0.518 0.104 2.495 0.396
Gna^Pose (iiM/mmol/kg)
Gna
