Osteoporosis-inhibitory properties of the hop special extract WS® 1242

Besides its use as an essential antimicrobial and flavouring ingredients in beer, hop has a long tradition as a mild sedative in European folk medicine. Presumably, this effect is mainly due to the content of α- and β-bitter acids, which were extensively studied for a long time. After the discovery of hop prenylnaringenins as potent phytoestrogens, the focus of interest has shifted towards the phenolic constituents of this plant. The main phenolic component in hops is xanthohumol (X), which is accompanied by smaller amounts of isoxanthohumol (IX) and 6- and 8-prenylnaringenin (6-PN, 8-PN). Although X possesses no or only week estrogenic activity it has been observed to exert significant cancer chemopreventive properties and to protect experimental animals against osteoporosis. Thus, it is suggested that hop extracts may be applied for the treatment of climacteric complaints and the prevention of postmenopausal reduction in bone density. For this purpose, we have developed the hop special extract WS® 1242, which is characterised by a content of 0.2% 8-PN, 0.8% 6-PN, 0.8% IX and 6.1% X. Estrogenic activity of WS® 1242 was determined in a competitive estrogens receptor (ER) binding assay. Binding of ³H-17β-estradiol to recombinant human ER-α and ER-β was inhibited at IC₅₀ concentrations of 1.2 and 1.6µg/ml, respectively. Estrogenic activity of WS® 1242 was also assessed by stimulation of alkaline phosphatase activity in Ishikawa cells. As an animal model for osteoporosis we used ovariectomized rats which were treated daily for 4 weeks with WS® 1242at doses of 50, 150 and 450mg/kg. The extract dose-dependently inhibited the reduction in density of the right femur. At the highest dose this effect was comparable to those of estradiol-3-O-benzoate (EB, 0.5mg/kg) and was accompanied by a parallel increase in the bone content of ash, calcium and phosphate. Furthermore, increased plasma levels of osteocalcin were reversed by administration of EB and WS® 1242 (statistically significant at a dose of 150mg/kg). However, in contrast to EB WS® 1242 did not display uterotrophic activity and did also not reverse the increased body weight gain in ovariectomized rats. The present results indicate that WS® 1242 possess interesting pharmacological activities which support is potential medicinal use in the treatment of osteoporosis.

Reference: Chadwick, L. R. et al. (2006) Phytomedicine 13: 119–131.