Lipid Profile and 5α-Reductase Inhibition Activity of Proprietary Ultrahigh-Pressure Supercritical Carbon Dioxide and Hexane Saw Palmetto Extracts

Abstract

Inhibition of 5α-reductase (5αR), which blocks the conversion of testosterone to its active metabolite, dihydrotestosterone, has been shown to impact further prostate enlargement (benign prostatic hyperplasia, or BPH). Clinical trials of standardized lipidosterolic extracts of Serenoa repens (LSESr), also known as standardized extracts of saw palmetto, have demonstrated improvement in lower urinary tract symptoms (LUTS) and delayed progression of BPH. The aim of this preclinical study was to compare two standardized LSESr, a proprietary ultrahigh-pressure supercritical carbon dioxide extract of S. repens (UHP-sCESr) and the well-established hexanic extract of S. repens (HESr), for both 5αR inhibition activity and lipid profiles. UHP-sCESr and HESr had nearly identical inhibition curves and comparable IC50 values for 5αR-1 (9.25 ± 0.87 and 9.86 ± 0.11 μg/mL, respectively; p = 0.43) and 5αR-2 (7.47 ± 0.07 and 7.72 ± 0.05 μg/mL, respectively; p = 0.0544). UHP-sCESr and HESr also had comparable lipid profiles based on similar total fatty acid levels (87.7% and 91.5%, respectively), weight/weight comparisons of individual fatty acids, and individual fatty acid ratios to lauric acid. In addition, UHP-sCESr meets the standard set by the United States Pharmacopeia (USP) monograph for authenticity and purity for a supercritical carbon dioxide (SCCO2) extract of saw palmetto, whereas HESr meets the standard set by the European Medicines Agency (EMA) for a well-established medicinal product. In conclusion, based on enzyme inhibition curves and IC50 values, a standardized lipid profile is important to achieve comparable mechanisms of action for lipidosterolic extracts of saw palmetto. UHP-sCESr offers a comparable, standardized LSESr for men with LUTS/BPH in regions where the proprietary HESr is not available.