Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Phytomedicine. 2022 Jul 20;102:154169. doi: 10.1016/j.phymed.2022.154169. Epub 2022 May 14.
Benign prostatic hyperplasia (BPH) is a urinary system disease with high prevalence among the middle and elder men. In BPH, proliferation of prostate cells and the imbanlance between androgen and estrogen are both important inducers. Previous studies have demonstrated that compounds from Ligustri Lucidi Fructus (LLF) and Ecliptae Herba (EH) are of phytoestrogenic or phytoandrogenic activities. The combination of LLF with EH at the ratio of 1:1 on crude drugs quantity is called Erzhi formula (EZF), which is used for in vivo research of our study.
This study aimed to investigate potential mechanisms of EZF and its active pharmaceutical ingredients on BPH in vitro and in vivo.
Therapeutic effects of EZF was evaluated in E/testosterone (1:100) induced BPH rats model. The pathological changes of prostate, concentrations of testosterone, DHT, E, PSA in rats' plasma and prostate were detected. The expressions of PCNA, AR, ERα, ERβ, SRD5A1, SRD5A2 were measured in BPH rat prostates and E-stimulated human benign prostatic epithelial cells (BPH-1).
EZF treatment significantly attenuated rat prostate enlargement, alleviated BPH pathological features, and decreased the expression of PCNA. The up-regulation of AR, ERα, SRD5A1/2 expressions, and down-regulation of ERβ expression at prostate of rat BPH model were significantly blocked by EZF administration. The expression levels of testosterone, DHT, E, PSA were strongly inhibited by EZF treatment. At the cellular level, ligustrosidic acid and echinocystic acid inhibited E-induced BPH-1 cell proliferation and PCNA expressions, which were consistent with the results in vivo. And these two ingredients also down-regulated the expressions of AR, ERα, SRD5A1/2 and up-regulated the expression of ERβ in BPH-1 cells.
EZF, ligustrosidic acid from LLF and echinocystic acid from EH showed inhibitive effects on BPH via down-regulating prostatic AR, ERα, SRD5A1/2 expressions and up-regulating ERβ expression.
良性前列腺增生（BPH）是一种泌尿系统疾病，中老年男性患病率较高。在 BPH 中，前列腺细胞的增殖和雄激素与雌激素之间的失衡都是重要的诱导因素。先前的研究表明，从女贞子（LLF）和旱莲草（EH）中提取的化合物具有植物雌激素或植物雄激素活性。以生药数量比 1:1 混合的女贞子和旱莲草称为二至方（EZF），用于本研究的体内研究。
本研究旨在探讨 EZF 及其活性药物成分对体外和体内 BPH 的潜在作用机制。
在 E/睾酮（1:100）诱导的 BPH 大鼠模型中评价 EZF 的治疗效果。检测大鼠前列腺的组织病理学变化、血浆和前列腺中睾酮、DHT、E、PSA 的浓度。测量 BPH 大鼠前列腺和 E 刺激的人良性前列腺上皮细胞（BPH-1）中 PCNA、AR、ERα、ERβ、SRD5A1、SRD5A2 的表达。
EZF 治疗显著减轻了大鼠前列腺肿大，缓解了 BPH 的病理特征，并降低了 PCNA 的表达。EZF 给药可显著阻断大鼠 BPH 模型前列腺中 AR、ERα、SRD5A1/2 表达的上调和 ERβ 表达的下调。EZF 治疗强烈抑制了 testosterone、DHT、E、PSA 的表达。在细胞水平上，齐墩果酸和猪苓酸抑制了 E 诱导的 BPH-1 细胞增殖和 PCNA 的表达，这与体内结果一致。这两种成分还下调了 BPH-1 细胞中 AR、ERα、SRD5A1/2 的表达，上调了 ERβ 的表达。
EZF、女贞子中的齐墩果酸和旱莲草中的猪苓酸通过下调前列腺 AR、ERα、SRD5A1/2 的表达和上调 ERβ 的表达对 BPH 具有抑制作用。
