Inhibitory Effects of Isoflavonoids on Rat Prostate Testosterone 5 alpha-Reductase

Testosterone 5 alpha-reductase inhibitors represent important therapeutic drugs for use against androgen-dependent diseases such as benign prostatic hyperplasia, male pattern baldness, and acne. We have searched for inhibitors of rat prostate testosterone 5 alpha-reductase in the cultured broths of many kinds of soil bacteria, and have found that cultured soybean-casein digest broths of certain bacterial strains have a potent inhibitory effect on the enzyme. We tested 10 selected isoflavonoids, including isoflavones and O-methylated isoflavones, for inhibitory effects on rat prostate testosterone 5 alpha-reductase to determine the important structural elements for inhibition of the enzyme. Genistein, biochanin A, equol, and 30,40,7-trihydroxyisoflavone showed considerably higher inhibitory effects whereas daidzein, formononetin, glycitein, prunetin, ipriflavone, and 40,7-dimethoxyisoflavone showed lower inhibitory effects. The IC50 values of genistein, biochanin A, equol, 3',4',7-trihydroxyisoflavone, and riboflavin, a positive control, for rat prostate testosterone 5 alpha-reductase were 710 mu M, 140 mu M, 370 mu M, 690 mu M, and 17 mu M, respectively. Daidzein, genistein, biochanin A, formononetin, and equol are already known to be testosterone 5a-reductase inhibitors, but this is the first characterization of 3',4',7-trihydroxyisoflavone as an inhibitor of the enzyme.