FlexPro MD®, a Combination of Krill Oil, Astaxanthin and Hyaluronic Acid, Reduces Pain Behavior and Inhibits Inflammatory Response in Monosodium Iodoacetate-Induced Osteoarthritis in Rats

Abstract

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.

Antarctic Krill Oil Ameliorates Monosodium Iodoacetate-Induced Irregularities in Articular Cartilage and Inflammatory Response in the Rat Models of Osteoarthritis

“…Our data show that MIA treatment induced matrix degradation and disrupted surface of the articular cartilage, resulting in the generation of an irregular surface, as revealed by histological analysis, and supplementation with FJH-KO in the this background reduced cartilage destruction. Previous studies have demonstrated that omega-3 and/or KO supplement reduced cartilage destruction and OARSI score [ 17 , 18 , 19 ].…”

“…In addition, they also reported that peptide from KO improved osteoarthritis via inhibition of HIF-2α-mediated death receptor apoptosis and -inflammatory cytokines expression [ 32 ]. Park et al showed that a mixture of krill oil, astaxanthin, and hyaluronic acid reduced serum levels of the pro-inflammatory cytokines as well as mRNA expression levels of iNOS and COX-2 in the knee joint from MIA-induced osteoarthritis [ 17 ]. These previous results and our previous results suggest that suggest that KO may reduce the inflammatory response and improve clinical symptoms of osteoarthritis.…”

Experimental Therapeutics for the Treatment of Osteoarthritis

“…Co-treatment of kaempferol and apigenin: collagen IIa1↑, aggrecan↑, SOX-9↑ gene expression. model: ACLT rat [ 148 , 149 ] Krill oil mixture with astaxanthin and HA Serum levels of articular cartilage degeneration biomarkers cartilage oligomeric matrix protein (COMP)↓ and crosslinked C-telopeptide of type II collagen↓, TNF-α↓, IL-1β↓, IL-6↓, mRNA of iNOS↓, COX-2↓, MMP-2 and −9↓, in knee joint tissue, probably via NF-κB model: MIA rat [ 150 ] Olive-derived polyphenols Olive, contains polyphenols: including hydroxytyrosol, tyrosol, oleocanthal and oleuropein anti-inflammatory, with antioxidant and autophagy-enhancing activities (via SIRT1) models: rabbit articular cartilage defect, human trials [ 151 ] Paeonia (P.) lactiflora and the gum resin of C. myrrha Traditional medicines, P. lactiflora root and C. myrrha gum resin, NO↓, iNOS↓, IL-1β↓, IL-6↓, COX-2↓, cartilage erosion and subchondral bone damage↓ model: MIA rat [ 128 ] Phyllanthus emblica Fruit extract, hyaluronidase and collagenase 2 activity↓, chondroprotection model: human OA articular cartilage explants [ 90 ] Quercetin Achyranthes bidentata , (Quercetin, baicalein, and berberine are contained), inhibitors of TNFα and IL-6 signaling, and tumor suppressor protein (TP)53, inflammation↓, apoptosis↓ model: rat chondrocytes+IL-1β [ 129 ] Resveratrol Grape seed extract, inhibits NF-κB signaling, TNFα↓, IL-1β↓, IL-6↓, IL-18↓, caspase-9/3 activity↓, SIRT1↓, PGE2↓ and NO↓, MMP-1↓, -3↓, -13↓, COX-2↓, collagen type II and ACAN restored, heme oxygenase 1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf-2)↑, hence, it negatively regulates genes involved in apoptosis, cell stress, autophagy, catabolism models: OA articular chondrocytes+IL-1β, MIA rat [ 152 , 153 ] Stinging nettle Stinging nettle, MMP-1↓, MMP-3↓, MMP-9↓ Hypothesized: inhibits NF-κB signaling model: human articular chondrocytes+IL-1β [ 154 ] Sulforaphane …”

Emerging Natural-Product-Based Treatments for the Management of Osteoarthritis

“…[ [210][211][212][213][214][215][216][217][218][219][220][221][222] Promotes bone formation by inhibiting NF-κB signaling.…”

“…Astaxanthin is a carotenoid (tetraterpenoid) that is produced naturally in the microalgae Haematococcus pluvialis and can be found in animals who feed on the algae, such as salmon, red trout, and crustaceans [ 215 ]. It has therapeutic properties against rheumatoid arthritis and osteoarthritis [ 216 , 217 , 218 , 219 , 220 ]. In OA, astaxanthin has shown potent antioxidant and anti-inflammatory activities on cartilage due to the activation of Nrf2–ARE signaling in chondrocytes [ 221 ].…”