Prenyl flavonoids in hops and beer – biochemical and biological activities

H. Schmandke, Nuthetal

Hop cones contain about 0.5 xanthohumol (XH), 0.01 isoxanthohumol (IXH), 0.12 desmethylxanthohumol (DMXH), 0.002 8-prenylnarigenin ( 8-PN ) and 0.01 6-prenylnaringenin (6-PN). The content of 6- and 8-PN and IXH in beer is also due to thermal isomerization of chalcones (DMXH or XH, resp.) into flavanones during the brewing process. The content in different beers may vary for XH from 5 to 690 µg/l, for IXH from 300 to 3440 µg/l , for 6-PN from 22 to560 µg/l and for 8-PN from 8 to 240 µg/l.

After oral administration of XH to rats, about 90 % (including XH-4’-O-glucuronide) were excreted unchanged with the faeces and about 9 % as metabolites. In the urine 0.35 % of the dose was detected (0.2 % as unchanged XH + 4’-O- and 4-O-glucuronides of XH).

After oral intake of IXH by humans, up to 4.4 % were renally excreted as 8-PN (after cleavage of conjugates). Of 8-PN taken by menopausal women, 0.23 % were renally excreted as free 8-PN and 8 % as glucuronide. However, 17 % of 8-PN in beer were renally excreted by men. This high renal excretion rate is probably due to the conversion of beer IXH into 8-PN in the organism.

The metabolites in the faeces originate from the stomach (gastric acid forms from XH, IXH and the 5-OH-derivative of XH), gut microorganisms and liver (excretion of XH and its metabolites with the faeces after iv injection of XH to rats; this fact suggests that these compounds are excreted with the bile into the gut).

Metabolites of XH in the faeces, and of XH, IXH and 8-PN in rat and human liver microsomes are predominantly formed by oxidation of the prenyl methyl group or in the ring system and by cyclization of the prenyl moiety with the hxdroxyl group at C2’ or C4’ of XH or at C7 of IXH and 8-PN, resp. An oral dose of 100 mg XH per kg b. w. and day to female rats did not affect the development of the animals over 2 generations.

XH fed to diabetic mice resulted in lower levels of plasma glucose and -triglyceride, hepatic triglyceride and cholesterol, and in lower weight of white adipose tissue.

The anticancerogenic potential of the prenyl flavonoids is characterized (1) by inhibition of the metabolic activation of pro-carcinogens due to inhibition of cytochrome P450 enzymes by XH, 8-PN and IXH; (2) by induction of carcinogen-detoxifying enzymes by XH and IXH (quinone reductase in cultured mouse hepatom cells); (3) by inhibition of tumor growth in an early state by XH in human colon cancer, breast cancer, ovarian cancer and leukemia cells in vitro; (4) by reduction of blood vessel growth (angiogenesis) by 8-PN in fertilized chicken eggs (XH was not tested).

XH shows antiestrogenic activity (reduction of uterine weight of juvenile female rats) while 8-PN is estrogenic (increase of uterine and vagina weights). In vitro, 8-PN has shown a high selective binding to human α-estrogen receptors.

Key words: Prenyl flavonoids / hops / beer / biochemical activities / biological activities

Sie finden den Artikel in deutscher Sprache in Ernährungs-Umschau 06/06 ab Seite 225.