Study On The Inhibitors Of 5α-Reductase And The Inhibitors Of DU145

Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are two of the more harmful prostatic diseases in the elderly men. The incidence of BPH and PCa goes up with the ageing population. Literature search shows that steroid 5a-reductase is a membrane-bound NADPH-dependent enzyme that catalyzes the reduction of testosterone (T) to the more potent androgen dihydrotestosterone(DHT), which promotes the development of BPH. The majority of PCa responds to antiandrogen therapy by temporary remission in its initial stages. However, most tumors will eventually relapse in an androgen-refractory state inevitably.A compounds library was established from ethanol extractor of several traditional Chinese herbal medicines(such as Plantago asiatica L., Rehmannia glutinosa, Alisma orientalis (Sam.) Juzep, Cyathula officinalis Kuan) via systematic solvent-extraction process and silica column chromatography.Fluorescence assay was chose as a method of screening 5α-reductase inhibitor, based on its veracity and precision compare with absorbency measure. The activity of 5a-reductase was evaluated through inspecting the reduction of NADPH in the enzyme catalyze process. The eventual conditions of determination were excitation wavelength 360 nm, emission wavelength 465 nm, NADPH 40 μM, T 20 μM, tissue extract 5 mg/ml, sample 100 μg/ml, finasteride 2 μM (positive control), total volume 120 μl, 37℃, 10 min. The results indicated that some ingredients of those Chinese herbal medicines had some degree of inhibitory effect, and the n-butanol extract from Alisma orientalis (Sam.) Juzep had more activity.With the measurement of 3-(4,5-dimethylthiazol-2yl) 2,5-diphenyltetrazolium bromide (MTT) colorimetry, a compound with the more potential to inhibit the growth of the DU145 (an androgen-independent human prostatic adenocarcinoma cell. IC(50)=25.02 μg/ml) was detected, The compound came from n-butanol extract of Plantago asiatica L. via silica column chromatography.