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Activation of pro-estrogens from hops by intestinal bacteria. Production of the phytoestrogen 8-prenylnaringenin. Sam Possemiers , Selin Bolca, Veerle Maervoet, Tom Van de Wiele, Arne Heyerick, Denis De Keukeleire & Willy Verstraete. Laboratory of Microbial Ecology & Technology (LabMET) - PowerPoint PPT Presentation
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Activation of pro-estrogens from hops by intestinal bacteria
Sam Possemiers, Selin Bolca, Veerle Maervoet, Tom Van de Wiele, Arne Heyerick, Denis De Keukeleire & Willy Verstraete
Production of the phytoestrogen 8-prenylnaringenin
Laboratory of Microbial Ecology & Technology (LabMET)http://labmet.ugent.be
“Plant constituents which structurally or functionally mimic the female estrogen 17β-estradiol”
Beneficial role in the prevention of osteoporosis, menopauzal complaints and cancers
Applications!
Phytoestrogens (1)
HO
CH3 OH
17β-estradiol
Phytoestrogens (2) 2 well known groups:
Isoflavones from soy: daidzein, genistein
Lignans from linseed, fruits, nuts…
O
OHO
OH
OH
genistein
HO
OH
OH
OH
OH
OH
O
O
Secoisolariciresinol(SECO)
Phytoestrogens (3) Common caracteristics:
Crucial activation by the intestinal microbiota Daidzein equol SECO enterodiol, enterolacton Strong influence on biological activity!
BUT: interindividual differences!!! E.g. only 1/3rd of population produces equol
Beneficial effects depend on microbial community composition
Phytoestrogens from hop (1)
Humulus lupulus L. (Hop)>Cannabaceae (+ Cannabis sativa L.)
Mainly used in beer industry But also source of the prenylflavonoid 8-prenylnaringenin (8-PN)
3rd group of phytoestrogens
Phytoestrogens from hop (2) Research topic:
Intestinal metabolism? Cfr other phytoestrogens: intestinal activation?
Hop prenylflavonoids: 8-prenylnaringenin (8-PN): very low concentrations
Isoxanthohumol (IX) and Xanthohumol (X): not estrogens but much higher concentrations.
Metabolism of 8-PN, IX and X?
Isoxanthohumol acts as pro-estrogen (1)
IX can be activated into 8-PN!
Isoxanthohumol acts as pro-estrogen (2)
Desmethyl-xanthohumol
+
6-Prenylnaringenin
OH
O
OH OH
OMe
Xanthohumol (X)
O
OH O
OH
OMe
Isoxanthohumol (IX)
Michael addition
OOH
OH O
OH
12
6
8
OOH
OH
OH
O
8-Prenylnaringenin (8-PN)
Michael addition
MicrobialO-
demethylation
OO H
O HOH
O H
Isoxanthohumol acts as pro-estrogen (3)
IX can be activated into 8-PN! Relevance:
8-PN conc in beer are too low for biological effects
Activation of IX: much higher exposure to 8-PN! BUT: interindividual differences
Interindividual differences?
Interindividual differences in vitro (1)
Experiment with 51 fecal samples Incubation immediately after defecation
BHI + fecal samples (5%) 25 mg/L IX 37°C, anaerobic conditions HPLC and LC/MS analysis
% high, moderate and slow 8-PN producers?
Possemiers et al., Journal of Nutrition, July 2006
Interindividual differences in vitro (2)
2/3!
Interindividual differences: 3 significant groups!
Interindividual differences in vivo (1)In vivo evaluation of the bioavailability and biotransformation of hop prenylflavonoids
5 day intervention study (5.5 mg IX/d) 50 postmenopauzal women urine collection:
Absorption prenylflavonoids Detection and identification of metabolites
Fecal sample collection In vitro IX into 8-PN conversion Molecular fingerprinting of intestinal community
In vivo (2): fecal samples
High (A), moderate (C) and slow (B) IX-converter
In vivo (3): urine
High (A), moderate (C) and slow (B) 8-PN excretion Good correlation between in vitro and in vivo!
Conclusions Intestinal transformation of hop flavonoids:
Interindividual differences 1/3rd converted IX into hopein (8-PN)
Good correlation in vitro and in vivo Intestinal bacteria are responsible for the conversion in vivo
IX acts as pro-estrogen in food and supplements Up to 4 mg IX/L in beer and 5 mg/supplement Possible health effects not negligible! Exposure dependent on intestinal microbial community!
Contact information Posters:
Possemiers et al. Bolca et al.
LabMET – Ghent UniversityCoupure Links 653B-9000 [email protected]://labMET.ugent.be/+32/9/264.59.76