Effects of hyaluronan alone or in combination with chondroitin sulfate and N-acetyl-d-glucosamine on lipopolysaccharide challenge-exposed equine fibroblast-like synovial cells

Kilborne, Allison H.; Hussein, Hayam; Bertone, Alicia L.

doi:10.2460/ajvr.78.5.579

Cited by 8 publications

(4 citation statements)

References 35 publications

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“…Synovial cell cultures exposed to lipopolysaccharide treatment, instead, were reported in the literature as a model to study the protective and anti-inflammatory effects of HA alone or in combination with CS and GlcN [34, 35]. In addition, through the NF-κB activation and IL-8 production, the synovial cells have been used to evaluate the anti-inflammatory response of food supplements with other potentially bioactive molecules (e.g., HA, collagen peptides, Boswellia serrata , devil’s claw, or curcumin).…”

Section: Discussionmentioning

confidence: 99%

Comparative Analyses of Pharmaceuticals or Food Supplements Containing Chondroitin Sulfate: Are Their Bioactivities Equivalent?

et al. 2019

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IntroductionOral supplementation of chondroitin sulfate (CS) and glucosamine (GlcN), symptomatic slow-acting molecules, is recommended by European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis and Musculoskeletal Diseases (ESCEO) and other European Union (EU) guidelines for the restoration of the articular cartilage surface in patients affected by osteoarthritis (OA). They are commercialized as pharmaceutical grade products and as food supplements in combination with plant extracts hyaluronic acid, methylsulfonylmethane, and other components. Food supplements do not need to undergo the strict regulatory controls of pharmaceutical grade products; thus, composition and contaminants that could be present may not be evidenced before commercialization and these uncertainties may give rise to concerns about the bioactivity of these formulations.MethodsIn this paper 10 different food supplements (FS) from diverse European countries were analyzed in comparison with two pharmaceutical grade products (Ph) using updated analytical approaches and biochemical cell-based assays. The purity, the titer, and the origin of CS in Ph and FS samples were initially assessed in order to successively compare the biological function. Both food supplements and pharmaceutical formulations were tested in vitro, using the same final CS concentration, on primary chondrocytes and synoviocytes in terms of (i) cell viability, (ii) activation of the NF-κB-mediated inflammation pathway, (iii) cartilage oligomeric matrix protein (COMP-2), IL-6, and IL-8 production.ResultsAll the FS presented a certain insoluble fraction; the CS and the GlcN contents were lower than the declared ones in 9/10 and 8/10 samples, respectively. All FS contained keratan sulfate (KS) at up to 50% of the total glycosaminoglycan amount declared on the label. Primary cells treated with the samples diluted to present the same CS concentration in the medium showed cytotoxicity in 7/10 FS while Ph preserved viability and reduced NF-κB, COMP-2, and secreted inflammatory cytokines.ConclusionAmong all samples tested, the pharmaceutical grade products demonstrated effective modulation of biomarkers counteracting the inflammation status and improving viability and the physiological condition of OA human primary chondrocyte and synoviocyte cells. In contrast to that, most FS were cytotoxic at the tested concentrations, and only 3/10 of them showed similarities to Ph sample behavior in vitro.FundingThis work was partially supported by PON01_1226 NUTRAFAST, MIUR Ministero dell’Università e della Ricerca Scientifica. Bioteknet financed two short-term grants for graduate technicians. The journal’s Rapid Service and Open Access fees were funded by IBSA CH.

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Section: Discussionmentioning

confidence: 99%

Comparative Analyses of Pharmaceuticals or Food Supplements Containing Chondroitin Sulfate: Are Their Bioactivities Equivalent?

et al. 2019

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“…The LMW-HA group, but not the HMW-HA group, showed a lower concentration of SF TNF-α and IL-6 than the TA group. Other studies reported that equine fibroblast-like synovial cells exposed to LPS showed increased concentrations of IL-6, but the cells treated with HMW-HA had significantly better viability and morphology scores and lower concentrations of IL-6 than the untreated LPS-exposed cells [33]. Furthermore, HMW-HA can suppress the LPS-activated PI3K/Akt pathway, leading to the downregulation of nuclear factor (NF)-κB with decreased IL-6 production through an interaction with intercellular adhesion molecule 1 [34].…”

Section: Discussionmentioning

confidence: 99%

Hyaluronic acid has chondroprotective and joint-preserving effects on LPS-induced synovitis in horses

et al. 2019

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The intra-articular use of hyaluronic acid (HA) for the treatment of synovitis and osteoarthritis is still controversial. As a consequence, corticosteroids remain the most frequently employed therapeutic agents, despite their potential systemic and local deleterious effects. This study examined the anti-inflammatory, antioxidant, and chondroprotective activities of low and high molecular weight hyaluronic acid (LMW-HA and HMW-HA) on lipopolysaccharide (LPS)-induced synovitis in horses compared to triamcinolone acetonide (TA). LPS was injected in the metacarpophalangeal joints, which were treated intra-articularly with either TA (as control) or LMW-HA or HMW-HA. Joint clinical evaluation and synovial fluid (SF) analysis were performed at 0, 8, 24, and 48 h. The white blood cell counts (WBC), prostaglandin E2 (PGE2), interleukin (IL)-1, IL-6, IL-10, tumor necrosis factor-α, chondroitin sulfate (CS) and HA concentrations, oxidative burst, and HA molecular weights were measured. TA reduced the lameness, swelling, and PGE2 release but increased the SF CS concentrations enormously at 24h and 48h, and decreased the SF HA modal molecular weight. These results indicate the breakdown of articular cartilage aggrecan and SF HA. In contrast, LMW-HA and HMW-HA were less effective in reducing the inflammation symptoms, but preserved the joints because only a modest increase in CS occurred at 24 h, decreasing at 48 h, and the SF HA was maintained. The HA-treatment also had anti-inflammatory actions, and LMW-HA was the most effective in reducing the release of cytokine. In summary, the HA treatment inhibited efficiently the digestion of cartilage proteoglycans and SF HA breakdown.

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“…GlcN can be obtained through the extraction of chitin from crustacean shells followed by both alkaline or acid hydrolyzes or by de novo chemical synthesis [5,9], and it is commercialized as stabilized salt of glucosamine or glucosamine sulfate [5]. Despite that, CS and GlcN are combined in pharmaceutical preparations and in food supplements to be orally administered as anti-osteoarthritis active principles even in long-term therapy [15]. The EULAR and the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis and Musculoskeletal Disease (ESCEO) have recommended daily dosages of CS and GlcN between 800 and 1200 mg and between 1250 and 1500 mg, respectively [4,8].…”

Section: Introductionmentioning

confidence: 99%

Fourier-transformed infrared spectroscopy, physicochemical and biochemical properties of chondroitin sulfate and glucosamine as supporting information on quality control of raw materials

2020

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Background Chondroitin sulfate (CS) and glucosamine (GLcN) are recommended for the restoration of the articular cartilage surface in patients affected by osteoarthritis. They are commercialized as pharmaceutical-grade products and as food supplements, and there are reports that they do not undergo the strict quality controls of pharmaceuticals. Herein, we evaluated the physicochemical parameters of two raw materials (CS and GlcN) obtained from two distinct suppliers in Brazil and compare the obtained data with the product specification provided by the manufacturer. Also, the homogeneity and purity grade of samples were analyzed by FT-IR spectroscopy. Results The organoleptic properties and solubility of CS and GlcN samples obtained from pharmacy analyses and the supplier’s specifications are in accordance with the standards required by the Brazilian Health Regulatory Agency (ANVISA). However, the intraclass correlation coefficient (ICC) and Bland Altman analysis of pH and the density values of samples are statistically different between the suppliers. In addition, FT-IR analyses indicated that there is non-homogeneity in the CS and GlcN samples tested, showing that both manufacturers distribute the drugs in different concentrations, although both declare the same concentration in the product technical specifications. Conclusion In summary, our study demonstrated that physicochemical parameters are insufficient to ensure product quality, and it is necessary to implement a more efficient protocol to ensure the quality of the final product. Graphical abstract

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Effects of hyaluronan alone or in combination with chondroitin sulfate and N-acetyl-d-glucosamine on lipopolysaccharide challenge-exposed equine fibroblast-like synovial cells

Cited by 8 publications

References 35 publications

Comparative Analyses of Pharmaceuticals or Food Supplements Containing Chondroitin Sulfate: Are Their Bioactivities Equivalent?

Comparative Analyses of Pharmaceuticals or Food Supplements Containing Chondroitin Sulfate: Are Their Bioactivities Equivalent?

Hyaluronic acid has chondroprotective and joint-preserving effects on LPS-induced synovitis in horses

Fourier-transformed infrared spectroscopy, physicochemical and biochemical properties of chondroitin sulfate and glucosamine as supporting information on quality control of raw materials

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