Combination of Ligustri Lucidi Fructus with Ecliptae Herba and their phytoestrogen or phytoandrogen like active pharmaceutical ingredients alleviate oestrogen/testosterone-induced benign prostatic hyperplasia through regulating steroid 5-α-reductase

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 E2/testosterone (1:100) induced BPH rats model. The pathological changes of prostate, concentrations of testosterone, DHT, E2, PSA in rats' plasma and prostate were detected. The expressions of PCNA, AR, ERα, ERβ, SRD5A1, SRD5A2 were measured in BPH rat prostates and E2-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, E2, PSA were strongly inhibited by EZF treatment. At the cellular level, ligustrosidic acid and echinocystic acid inhibited E2-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.