Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China; Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China; Laboratory of Pharmacology of TCM Formulae Co-Constructed by the Province-Ministry, Tianjin University of TCM, Tianjin 300193, China.
Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China; Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
Toxicol Appl Pharmacol. 2019 Oct 15;381:114637. doi: 10.1016/j.taap.2019.114637. Epub 2019 Jun 22.
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.
雌激素和雄激素在良性前列腺增生（BPH）的发展中起着关键作用。雌激素受体（ERs）、雄激素受体（AR）和芳香酶，即雄激素转化为雌激素的关键转换酶，被认为是 BPH 治疗的有效靶点。含有补骨脂素（Ba）的草药补骨脂 Psoralea corylifolia 长期以来一直被用于治疗 BPH 患者，而 Ba 所涉及的作用和调节机制仍不清楚。人前列腺细胞系 WPMY-1 和 BPH-1 以及雌二醇/睾酮诱导的 BPH 大鼠被用作体外和体内模型。Ba 显著抑制了 WPMY-1 和 BPH-1 细胞的增殖。在 E2/T 诱导的 BPH 模型中，Ba 处理也显著抑制了前列腺的增大，降低了 PI 值，减少了围腺体平滑肌层的厚度，并下调了 PCNA 和平滑肌细胞标志物 α-SMA 的表达，这些在 BPH 大鼠中均高度诱导。此外，Ba 刺激的 WPMY-1 细胞中芳香酶的基础和 PGE2 诱导的表达减少，而 Ba 刺激的 BPH-1 细胞中 ERβ 的表达高度增加，这与体内 Ba 组的发现一致。Ba 诱导了 BPH-1 细胞中的 ERE 活性，就像 E2 一样；然而，沉默 ERβ 而不是 ERα，阻断了 Ba 诱导的 ERE 活性，而 E2 仍然表现出显著的 ERE 活性，这表明 Ba 对雌激素信号的调节特别通过 ERβ。总之，通过下调基质芳香酶和上调上皮 ERβ，Ba 有助于平衡雌激素和雄激素信号，并进一步抑制 BPH 的发展。
