Potency of a novel saw palmetto ethanol extract, SPET-085, for inhibition of 5alpha-reductase II.
BACKGROUND
The nicotinamide adenine dinucleotide phosphate (NADPH)-dependent membrane protein 5alpha-reductase irreversibly catalyses the conversion of testosterone to the most potent androgen, 5alpha-dihydrotestosterone (DHT). In humans, two 5alpha-reductase isoenyzmes are expressed: type I and type II. Type II is found primarily in prostate tissue. Saw palmetto extract (SPE) has been widely used for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH). The mechanisms of the pharmacological effects of SPE include the inhibition of 5alpha-reductase, among other actions. Clinical studies of SPE have been equivocal, with some showing significant results and others not. These inconsistent results may be due, in part, to varying bioactivities of the SPE used in the studies.


METHODS
The aim of the present study was to determine the in vitro potency of a novel saw palmetto ethanol extract (SPET-085), an inhibitor of the 5alpha-reductase isoenzyme type II, in a cell-free test system. On the basis of the enzymatic conversion of the substrate androstenedione to the 5alpha-reduced product 5alpha-androstanedione, the inhibitory potency was measured and compared to those of finasteride, an approved 5alpha-reductase inhibitor.


RESULTS
SPET-085 concentration-dependently inhibited 5alpha-reductase type II in vitro (IC(50)=2.88+/-0.45 microg/mL). The approved 5alpha-reductase inhibitor, finasteride, tested as positive control, led to 61% inhibition of 5alpha-reductase type II.


CONCLUSIONS
SPET-085 effectively inhibits the enzyme that has been linked to BPH, and the amount of extract required for activity is very low compared to data reported for other extracts. It can be concluded from data in the literature that SPET-085 is as effective as a hexane extract of saw palmetto that exhibited the highest levels of bioactivity, and is more effective than other SPEs tested. This study confirmed that SPET-085 has prostate health-promoting bioactivity that also corresponds favorably to that reported for the established prescription drug standard of therapy, finasteride.
Pais
Pilar
P
Euromed, 08100 Mollet del Vallès, Barcelona, Spain. ppais@euromed.es
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D058891:5-alpha Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000726:Androgen Antagonists / Q000627:therapeutic use; D002474:Cell-Free System; D004353:Drug Evaluation, Preclinical; D018120:Finasteride / Q000627:therapeutic use; D057809:HEK293 Cells; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D011470:Prostatic Hyperplasia / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D028024:Serenoa
D058891:5-alpha Reductase Inhibitors; D000726:Androgen Antagonists; D010936:Plant Extracts; C554077:SPET 085; D018120:Finasteride; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C040972:saw palmetto extract