Osteoarthritis (OA) is a degenerative joint disease and a leading cause of adult disability. Since there is no cure for OA and no effective treatment to slow its progression, current pharmacologic treatments, such as analgesics and non-steroidal anti-inflammatory drugs (NSAIDs), only alleviate symptoms, such as pain and inflammation, but do not inhibit the disease process. Moreover, chronic intake of these drugs may result in severe adverse effects. For these reasons, patients have turned to the use of various complementary and alternative approaches, including diverse dietary supplements and nutraceuticals, in an effort to improve symptoms and manage or slow disease progression. The present study was conducted to evaluate the anti-osteoarthritic effects of FlexPro MD^® (a mixture of krill oil, astaxanthin, and hyaluronic acid; FP-MD) in a rat model of OA induced by monosodium iodoacetate (MIA). FP-MD significantly ameliorated joint pain and decreased the severity of articular cartilage destruction in rats that received oral supplementation for 7 days prior to MIA administration and for 21 days thereafter. Furthermore, FP-MD treatment significantly reduced serum levels of the articular cartilage degeneration biomarkers cartilage oligomeric matrix protein (COMP) and crosslinked C-telopeptide of type II collagen (CTX-II), and the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), as well as mRNA expression levels of inflammatory mediators, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and matrix-degrading enzymes, matrix metalloproteinase (MMP)-2 and MMP-9, in the knee joint tissue. Our findings suggest that FP-MD is a promising dietary supplement for reducing pain, minimizing cartilage damage, and improving functional status in OA, without the disadvantages of previous dietary supplements and medicinal agents, including multiple adverse effects.

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.