Cactus flower extracts may prove beneficial in benign prostatic hyperplasia due to inhibition of 5α reductase activity, aromatase activity and lipid peroxidation

1998 ◽  
Vol 26 (4) ◽  
pp. 265-270 ◽  
Author(s):  
Adi Jonas ◽  
Gennady Rosenblat ◽  
Daniel Krapf ◽  
William Bitterman ◽  
Ishak Neeman
Keyword(s):  
Lipid Peroxidation ◽  
Benign Prostatic Hyperplasia ◽  
Reductase Activity ◽  
Prostatic Hyperplasia ◽  
Aromatase Activity

Stroma of human benign prostatic hyperplasia: preferential tissue for androgen metabolism and oestrogen binding

1981 ◽  
Vol 96 (3) ◽  
pp. 422-432 ◽  
Author(s):  
M. Krieg ◽  
G. Klötzl ◽  
J. Kaufmann ◽  
K. D. Voigt
Keyword(s):  
Benign Prostatic Hyperplasia ◽  
Binding Sites ◽  
Reductase Activity ◽  
Enzyme Reaction ◽  
Prostatic Hyperplasia ◽  
Binding Studies ◽  
Normal Prostate ◽  
Layer Chromatography ◽  
Androgen Binding ◽  
Tissue Fraction

Abstract. Because of the well known stromal-epithelial interaction of various urogenital organs, it was of interest to compare quantitatively steroid metabolism and binding in epithelium (E) and stroma (S) of the human benign prostatic hyperplasia (BPH). Testosterone 5α-reductase activity was determined by thin-layer chromatography and androgen as well as oestrogen binding sites by a charcoal adsorption technique after a steroid incubation period of 18 h at 0°C, using methyltrienolone (R1881) and oestradiol-17β as tritiated ligands and unlabelled R1881 and diethylstilboestrol as the respective competitors. The main results were as follows: (1) using biochemical markers (acid phosphatase, hydroxyproline), an on average 17% contamination of E by S and 6% of S by E was found, (2) the molar optimum of NADPH for the enzyme reaction was nearly identical in E and S, ranging between 1 and 0.1 mm, (3) the apparent Michaelis constant (Km) of 5α-reductase was in both fractions identical, the mean being 0.15 (μm, (4) the maximal rate of 5α-reductase activity (pmol 5α-reduced metabolites · mg protein−1 · 1 h−1) was 161 ± 28 (sem; n = 20), 66 ± 4.6 and 148 ± 6.6 in S, E and whole tissue fraction of BPH, respectively. In two normal prostates the means were: 88, 53 and 73, respectively, (5) the androgen binding sites were evenly distributed between the cytosol of E and S, while measurable oestrogen binding sites were found in 42% of the analyzed S but only in 5% of analyzed E. In conclusion: the 2.4 times higher 5·-reductase activity in S compared to E of the BPH is responsible for the about 2 to 2.5 times higher activity in the whole tissue fraction of BPH if compared with the normal prostate. Furthermore, due to our preliminary binding studies, oestrogens might play an important role in the S fraction of BPH.

Effect of Pregnenolone Derivatives on the Selective Inhibition of 5α-Reductase 2 Activity

2020 ◽  
Vol 15 (3) ◽  
pp. 179-189
Author(s):  
Marisa Cabeza ◽  
Lucero Bautista ◽  
Eugene Bratoeff ◽  
Juan Soriano ◽  
Yvonne Heuze
Keyword(s):  
Biological Activity ◽  
Benign Prostatic Hyperplasia ◽  
Animal Studies ◽  
Reductase Activity ◽  
Selective Inhibition ◽  
Causative Factor ◽  
Prostatic Hyperplasia ◽  
Hamster Model ◽  
Ic50 Values

Background: Benign prostatic hyperplasia and prostate cancer are androgen-dependent diseases, and dihydrotestosterone (DHT), a 5α-reduced metabolite of testosterone (T), has been implicated as a causative factor in the progression of these diseases. The 5α-reductase enzyme (5α-R) converts T to DHT, which is responsible for increasing cell proliferation, and hence inhibition of this enzyme could lead to potential treatments for these afflictions. Objective: This study focused on evaluating the biological activity of three series of pregnenolone derivatives as inhibitors of 5α-R and as antiandrogens on androgen-dependent glands. Method: To determine the biological activity of these compounds, we evaluated the effect of each one on suppressing the activity of both types of isozymes of 5α-R (1 and 2) by 50% (IC50). Using animal studies, we assessed the effect of these derivatives on the weight of the prostate, seminal vesicles, and diameter of the flank organs of castrated hamsters previously dosed with 1 mg/Kg T. Results: In vitro experiments showed that derivatives 1f, 2b, and 3d were very effective inhibitors of the activity of 5α-R2, showing IC50 values of 21.8, 20, and 15 nM, respectively. Derivatives 2b and 3b showed a lower inhibition effect on 5α-R1. : The data also indicated that derivatives 2b, 1f, 3b, and 3d were very active in reducing prostate weight in the hamster model of benign prostatic hyperplasia. Discussion: Pharmacological experiments showed that pregnenolone derivatives possess an antiandrogenic effect because of the inhibition of DHT production in androgen-dependent glands. Conclusion: The pregnenolone derivatives studied suppressed type 2 5α-reductase activity and because of this, the weight and dimension of androgen-dependent organs were decreased.

scholarly journals Effects of a new steroidal aromatase inhibitor, TZA-2237, and/or chlormadinone acetate on hormone-induced and spontaneous canine benign prostatic hyperplasia

2000 ◽  
pp. 543-554 ◽  
Author(s):  
K Ito ◽  
Y Fukabori ◽  
Y Shibata ◽  
K Suzuki ◽  
M Mieda ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Benign Prostatic Hyperplasia ◽  
Aromatase Inhibitor ◽  
Muscle Growth ◽  
Group Iv ◽  
Prostatic Hyperplasia ◽  
Aromatase Activity ◽  
Group Iii ◽  
Chlormadinone Acetate ◽  
Group I

OBJECTIVE: It has been known for many years that human benign prostatic hyperplasia (BPH) is composed predominantly of hyperplastic stromal cells rather than epithelial cells. In the present study the effects of a new steroidal aromatase inhibitor on hormone-induced and spontaneous canine BPH were investigated. METHODS: (1) Effects of TZA-2237 on hormone-induced canine BPH. Ten castrated beagles were administered testosterone and androstenedione 6 days/week for 8 months, and divided randomly into three groups after 2 months of treatment as follows. Group I served as controls, Group II was given 0.5 and Group III was given 2.5 mg/kg/day TZA-2237 5 days/week for 6 months. (2) Effects of TZA-2237 on spontaneous canine BPH. Twenty aged beagles with BPH were divided into five groups, Group IV was untreated, Group V was treated with 1 and Group VI with 5mg/kg/day TZA-2237 5 days/week for 31 weeks. Group VII was treated with 5mg/kg/day Atamestane and Group VIII was treated with 0.3 mg/kg/day chlormadinone acetate (CMA) 5 days/week. (3) Effects of TZA-2237 combined with CMA on spontaneous canine BPH. Three aged beagles with BPH were treated with 1mg/kg/day TZA-2237 and 0.03 mg/kg/day CMA 5 days/week for 20 weeks (Group IX) and a further three aged beagles with BPH were treated with 0.3 mg/kg/day CMA alone 5 days/week (Group X). RESULTS: Hormone-induced prostatic growth was significantly suppressed in group III compared with that in other groups. In Group III, the intraprostatic aromatase activity, estradiol level and androgen receptor content decreased significantly in comparison with the values in Group I. The prostatic weights in Groups V, VI and VII increased significantly in comparison with the weight in Group IV. Serum LH and testosterone levels in Groups V, VI, and VII increased significantly in comparison with the level in Group IV. The prostatic weight in Group IX was decreased only slightly, but the smooth muscle component was decreased significantly. CONCLUSIONS: TZA-2237 is a new, unique and effective aromatase inhibitor that causes inhibition of both epithelial and stromal compartments in hormone-induced canine BPH. Dual inhibition of androgen and estrogen resulted in inhibition of smooth muscle growth, and should prove effective as a new method of treatment given the atrophic effects on not only the epithelium but also the stroma in human BPH.

scholarly journals Serenoa repens extracts: In vitro study of the 5α-reductase activity in a co-culture model for Benign Prostatic Hyperplasia

2018 ◽  
Vol 90 (3) ◽  
pp. 199-202 ◽  
Author(s):  
Daniela Buonocore ◽  
Manuela Verri ◽  
Laura Cattaneo ◽  
Sara Arnica ◽  
Michele Ghitti ◽  
...  
Keyword(s):  
Benign Prostatic Hyperplasia ◽  
Reductase Activity ◽  
Ethanol Extract ◽  
Prostatic Hyperplasia ◽  
Type I ◽  
Serenoa Repens ◽  
Culture Model ◽  
Hexane Extracts ◽  
Ethanol Extracts

Objectives. Benign Prostatic Hyperplasia (BPH) is a form of benign tumor that occurs in humans mainly with ageing. It affects more than 50% of over 50 years old males and it is characterized by an increased synthesis of dihydrotestosterone (DHT), due to the 5α-reductase activity. The BPH therapeutic approach mainly uses 5α-reductase inhibitors, such as the active compounds present in the extracts deriving from species Serenoa repens. Many lipidosterolic extracts are available on the market, which are obtained with different solvents, among them ethanol is recognized as non-toxic and has less handling risks than hexane. The purpose of the present experimental study was to investigate in-vitro the potency of an ethanol extract of S. repens comparing it with an n-hexane one. Materials and methods. Two different lipido-sterolic extracts of S. repens have been tested: ethanol extract and n-hexane extract, two batches for each one. The inhibitory action of the extract was evaluated estimating in-vitro the activity of enzyme 5α-reductase type I (5α-RI), which was mainly active under the experimental condition of pH 7.5. DHT amount, synthesized from testosterone (1 μM), was evaluated in a co-culture model of epithelial cells and fibroblasts resulting from prostatic biopsy of a patient with BPH.Results. The analysis of the resulting dose-response curves showed that the entire S. repens extracts inhibited the 5α-RI showing no difference between the two kinds of extract or between the batches. The resulting IC50 values were the following: 8.809 (95% CI = 5.133-15.56) and 9.464 (95% CI = 5.094- 18.27) for ethanol extracts; 11.08 (95% CI = 6.389-19.98) and 12.72 (95% CI = 7.758-21.53) for n-hexane extracts. Conclusions. The potency of ethanol extracts of S. repens was comparable with the one of n-hexane extracts.

scholarly journals Inhibitory Effect of Yongdamsagan-Tang Water Extract, a Traditional Herbal Formula, on Testosterone-Induced Benign Prostatic Hyperplasia in Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Eunsook Park ◽  
Mee-Young Lee ◽  
Woo-Young Jeon ◽  
Nari Lee ◽  
Chang-Seob Seo ◽  
...  
Keyword(s):  
Benign Prostatic Hyperplasia ◽  
Reductase Activity ◽  
Water Extract ◽  
Inhibitory Effect ◽  
Prostatic Hyperplasia ◽  
Herbal Formula ◽  
Oral Gavage ◽  
Ki 67 ◽  
Proliferation Markers ◽  
Glutathione Reductase Activity

Yongdamsagan-tang, a traditional herbal formula, is used widely for the treatment of inflammation and viral diseases. In this study, we investigated whether Yongdamsagan-tang water extract (YSTE) affects testosterone propionate- (TP-) induced benign prostatic hyperplasia (BPH) in a rat model. To induce BPH, rats were injected subcutaneously with 10 mg/kg of TP every day. YSTE was administrated daily by oral gavage at doses of 200 and 500 mg/kg along with the TP injection. After 4 weeks, prostates were collected, weighed, and analyzed. The relative prostrate weight was significantly lower in both YSTE groups (200 and 500 mg/kg/day) compared with the TP-induced BPH group. YSTE administration reduced the expression of proliferation markers PCNA, cyclin D1, and Ki-67 and the histological abnormalities observed in the prostate in TP-induced BPH rats. YSTE attenuated the increase in the TP-induced androgen concentration in the prostate. The YSTE groups also showed decreased lipid peroxidation and increased glutathione reductase activity in the prostate. These findings suggest that YSTE effectively prevented the development of TP-induced BPH in rats through antiproliferative and antioxidative activities and might be useful in the clinical treatment of BPH.

Stromal 5α-reductase activity is elevated in benign prostatic hyperplasia

1980 ◽  
Vol 94 (2) ◽  
pp. 284-288 ◽  
Author(s):  
R. P. Wilkin ◽  
N. Bruchovsky ◽  
T. K. Shnitka ◽  
P. S. Rennie ◽  
T. L. Comeau
Keyword(s):  
Benign Prostatic Hyperplasia ◽  
Specific Activity ◽  
Reductase Activity ◽  
Hydroxysteroid Dehydrogenase ◽  
Prostatic Hyperplasia ◽  
Primary Site ◽  
Human Prostate ◽  
The Mean ◽  
Abnormal Condition

Abstract. The activities of 5α-reductase and 3α(β)-hydroxysteroid dehydrogenase were assayed in homogenates of stroma and epithelium obtained from 3 normal, 9 hyperplastic and 2 carcinomatous human prostates. Irrespective of the normal or abnormal condition of the prostate, the localization of 5α-reductase was predominantly in stroma whereas the reductive and oxidative activities of 3α(β)-hydroxysteroid dehydrogenase were more evenly divided between stroma and epithelium. Furthermore, the mean specific activity of 5α-reductase in hyperplastic stroma at 84.6 ± 13.1 (± sem) pmol 30 min−1 mg protein−1 was almost 3 times greater (Student's t-test, P < 0.05) than the corresponding value in normal stroma, 31.6 ± 7.2 pmol mg protein−1 30 min−1. We conclude that the stroma is the primary site of conversion of testosterone to dihydrotestosterone in the human prostate owing to the prevalence in stroma of 5α-reductase, and that benign prostatic hyperplasia is characterized by an increased amount of stromal 5α-reductase activity.

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