Bakuchiol suppresses oestrogen/testosterone-induced Benign Prostatic Hyperplasia development through up-regulation of epithelial estrogen receptor β and down-regulation of stromal aromatase

Highlights: • Bakuchiol suppresses BPH progress in rats. • Bakuchiol activates ERβ expression and activity in prostatic epithelial cells. • Bakuchiol inhibits PGE2-induced aromatase expression in prostate stromal cells. • ERβ and aromatase are the two targets that contribute to Bakuchiol-suppressed BPH. -- Abstract: Estrogens and androgens play critical roles during benign prostatic hyperplasia (BPH) development. Estrogen receptors (ERs), androgen receptor (AR) and aromatase, the key conversion enzyme of androgen to estrogen, are thought to be the effective targets for BPH treatment. Bakuchiol (Ba)-containing herb Psoralea corylifolia has been long-termed used for BPH patients in traditional Chinese medicine while the role and regulatory mechanism of Ba involved remain unclear. Human prostatic cell lines WPMY-1 and BPH-1 and oestrodial/testosterone-induced BPH rats were used as the in vitro and in vivo models. Ba significantly inhibited the proliferation of WPMY-1 and BPH-1 cells. In E2/T-induced BPH model, Ba treatment also significantly inhibited the enlargement of prostate, decreased PI values, reduced the thickness of periglanular smooth muscle layer, and down-regulated the expressions of PCNA and smooth muscle cell marker α-SMA, all of which were highly induced in BPH rats. Moreover, the basal and PGE2-induced expressions of aromatase were reduced in Ba-stimulated WPMY-1 cells, while the expression of ERβ was highly increased in Ba-stimulated BPH-1 cells, both of which are consistent with the findings in Ba group in vivo. Ba induced ERE activity in BPH-1 cells as E2 did; however, silence of ERβ not ERα, blocked Ba-induced ERE activity while E2 still exhibited the significant ERE activity, indicating the regulation of estrogen signaling by Ba is particularly via ERβ. In conclusion, by down-regulation of stromal aromatase and up-regulation of epithelial ERβ, Ba contributes to the balance of estrogen and androgen signaling and further inhibits BPH development.