An inhibitory effect of Berberine from herbal Coptis chinensis Franch on rat detrusor contraction in benign prostatic hyperplasia associated with lower urinary tract symptoms.

ETHNOPHARMACOLOGICAL RELEVANCE: Coptis chinensis Franch (CCF), also known as Huang Lian in China, is a traditional Chinese medicine that commonly used for more than 2000 years. Clinically, CCF often used as anti-inflammatory, immune regulation and other effects. It has been reported that the decoction containing CCF can be used for the treatment of benign prostatic hyperplasia (BPH) or lower urinary tract symptoms (LUTS). AIM OF THE STUDY: This research aims to investigate the effect of CCF on inhibition of BPH development in vivo and in vitro, and further identify the active compound (s) and the possible mechanism involved in BPH-related bladder dysfunction. MATERIALS AND METHODS: Oestrodial/testosterone-induced BPH rat model was established as the in vivo model. The prostate index (PI) was calculated, the pathogenesis was analyzed and the micturition parameters were determined in the shamed-operated, BPH model and BPH + CCF groups after 4-week administration. The tension in detrusor strips was then assessed upon KCl or ACh stimulation with or without incubation of CCF or active compounds. To further investigate the signaling involved, rat detrusor cells were cultured as the in vitro models, the instantaneous calcium influx was measured and the ROCK-1 expression was detected. RESULTS: Increased PI value and the aggravated prostatic pathology were observed with voiding dysfunction in BPH rats, which were significantly blocked by oral CCF taken. ACh or KCl-induced contractile responses in detrusor strips were significantly inhibited and the micturition parameters were improved when incubation with CCF or its active compounds such as berberine. Both CCF and berberine suppressed the cellular calcium influx and ROCK-1 expression upon ACh stimulation, demonstrating that berberine was one of the active compounds that contributed to CCF-improved micturition symptoms and function. CONCLUSIONS: Taken together, our findings give evidence that CCF and its active compound berberine inhibited BPH and bladder dysfunction via Ca2+ and ROCK signaling, supporting their clinical use for BPH and BPH-related LUTS treatment.

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

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 ERß 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 ERß 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 ERß. In conclusion, by down-regulation of stromal aromatase and up-regulation of epithelial ERß, Ba contributes to the balance of estrogen and androgen signaling and further inhibits BPH development.