| BACKGROUND: Recent our investigation showed that the extract from Valeriana wallichii DC (Zhizhuxiang Conentration) decreased the size of the prostate of the health rat, suggesting the therapeutic potential of Zhizhuxiang Concentration for benign prostatic hyperplasia (BPH). OBJECTIVE: To study the suppressive effect and the mechanism of action of Zhizhuxing Concentration on benign prostatic hyperplasia. METHODS: (1 ) In the process of the preparation of extract from Valeriana wallichii DC, the content of total valtratums were used as standard to screen the technologies of extraction and concentration and to prescribe the content of total valtratums in the medicinal material and its extract. The extracts were also prepared for the pharmacology and mechanism studies of Valeriana wallichii DC. (2) The effects of Zhizhuxing Concentration were evaluated in castrated and health rats or mice. Animals were injected subcutaneously with testosterone propionate 1 mg/kg to induce the BPH, simultaneously were irrigated into stomach with Zhizhuxiang Concentration extract 10g/kg,. 5.0g/kg, 2.5 g/kg daily for 30 days. The prostatic ventral lobe was excised and weighed for evaluating the effects of Zhizhuaxiang Concentraton on benign prostatic hyperplasia. The main organs were examined for their histopathological changies. (3) The acute and chronic toxicities were also evaluated in health rats and mice using traditional pharmacology methods. (4) Next we investigate the effect of Zhizhuxiang Concentration on the metabolism of androgen in vivo with BPH rats. Testosterone (T) and dihydrotestosterone (DHT) contents in rats serum and prostates were measured by enzyme-linkbed immunoassays (ELISA). (5) A fluorentscent method measuring 5 a-reductaseactivity was developed in vitro for investigate the mechanism of Zhizhuxiang Concentration action. To confirm further the function and specific property of Zhizhuxiang Concentration targeting to 5a-reductase, the two isozymes genes of human 5a-reductase (5AR1 ^0 5AR2) were transfected and expressed stably in HEK293 and CHO cells, respectively. The effects of Zhizhuxiang Concentration on the metabolism of androgen in vitro were also investigated in both cell lines by ELISA. RESULTS: Zhizhuxiang was extracted with five times of 95% ethanol by means of maceration,and then concentrate the extraction into Zhizhuxiang Concentration (per ml. containing 6g raw materials) under 40°C. Testosterone increase the wet weight of prostated of rats and induces hyperplasia in BPH model group (PO.05). Like finasteride, Zhizuxiang Conentration extract significantly reduced prostate weight and index of BPH rats induced by testosterone, especially significant in high dose group (PO.01). Histopathological examination results showed that Zhizhuxiang Concentration extract with high-dose significantly improves the diameter, perimeter and area of prostatic gland lumen in BPH rat. The acute toxicity studies showed that the LD50 was 85.87g/kg after administration of Zhizhuxiang Concentration extract to mice. The maximum tolerated dose in rats was 60.0g/kg per day; The chronic toxicity study showed that no adverse effects were seen at a multiple oral dose of 18g/kg per day up to 13 weeks in rats. There were no changes in blood counts, blood chemistry parameters and no pathological changes in visceral organs including liver, kidneys, spleen, thymus and other organs, no change even at the end of the recovery period. DHT concentrations in the serum and prostates were significantly reduced when Zhizhuxiang Concentration extract was administered...
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