No evidence for the in vivo activity of aromatase-inhibiting flavonoids

Abstract

Measurements of the aromatase-inhibiting and antioxidative capacities of flavonoids in vitro showed that slight changes in flavonoid structure may result in marked changes in biological activity. Several flavonoids such as 7-hydroxyflavone and chrysin (5,7-dihydroxyflavone) were shown to inhibit the formation of 3H-17β-estradiol from 3H-androstenedione (IC 50<1.0 μM) in human choriocarcinoma JEG-3 cells and in human embryonic kidney cells HEK 293 transfected with human aromatase gene (Arom+HEK 293). Flavone and quercetin (3,3′,4′,5,7-pentahydroxyflavone) showed no inhibition (IC 50>100 μM). None of the requirements for optimal antioxidative capacity (2,3-double bond with 4′-hydroxy group, 3-hydroxyl group, 5,7-dihydroxy structure and the orthodihydroxy structure in the B-ring) is relevant for the maximum inhibition of aromatase by flavonoids. After oral administration to immature rats at a dose of 50 mg/kg body weight, which considerably exceeds amounts found in daily human diets, neither aromatase-inhibiting nonestrogenic flavonoids, such as chrysin, nor estrogenic flavonoids, such as naringenin and apigenin, induced uterine growth or reduced estrogen- or androgen-induced uterine growth. The inability of flavonoids to inhibit aromatase and, consequently, uterine growth in short-term tests may be due to their relatively poor absorption and/or bioavailability.