Disposition of hop prenylflavonoids in human breast tissue

Abstract

Hop-derived products may contain xanthohumol (XN), isoxanthohumol (IX), and the potent phytoestrogen 8-prenylnaringenin (8-PN). To evaluate the potential health effects of these prenylflavonoids on breast tissue, their concentration, nature of metabolites, and biodistribution were assessed and compared with 17beta-estradiol (E(2)) exposure. In this dietary intervention study, women were randomly allocated to hop (n=11; 2.04 mg XN, 1.20 mg IX, and 0.1 mg 8-PN per supplement) or control (n=10). After a run-in of >or=4 days, three supplements were taken daily for 5 days preceding an aesthetic breast reduction. Blood and breast biopsies were analyzed using HPLC-ESI-MS/MS. Upon hop administration, XN and IX concentrations ranged between 0.72 and 17.65 nmol/L and 3.30 and 31.50 nmol/L, and between 0.26 and 5.14 pmol/g and 1.16 and 83.67 pmol/g in hydrolyzed serum and breast tissue, respectively. 8-PN however, was only detected in samples of moderate and strong 8-PN producers (0.43-7.06 nmol/L and 0.78-4.83 pmol/g). Phase I metabolism appeared to be minor (approximately 10%), whereas extensive glucuronidation was observed (> 90%). Total prenylflavonoids showed a breast adipose/glandular tissue distribution of 38/62 and their derived E(2)-equivalents were negligible compared with E(2) in adipose (384.6+/-118.8 fmol/g, p=0.009) and glandular (241.6+/-93.1 fmol/g, p<0.001) tissue, respectively. Consequently, low doses of prenylflavonoids are unlikely to elicit estrogenic responses in breast tissue.

FIGURE 1

Structures of the most important prenylflavonoids found in hop-derived products: XN, IX, and 8-PN.

FIGURE 2

SRM trace chromatograms of cis and trans alcohols of IX (1a,b; m/z 369/119/249) and 8-PN (2a,b; m/z 355/119/235) (A) standards in control urine and (B) in hydrolyzed urine after prenylflavonoid supplementation.

FIGURE 3

SRM trace chromatograms of monoglucuronides (1 and 3) and aglycones (2 and 4) of IX (m/z 353/119/233) and 8-PN (m/z 339/119/219) in (A) non-hydrolyzed and (B) hydrolyzed urine after prenylflavonoid supplementation.

FIGURE 4

Disposition of XN, IX, and 8-PN in breast adipose and glandular tissue after prenylflavonoid supplementation. Mean values of duplicate extractions with single HPLC-MS/MS measurements.