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Nakamura F, Ikemizu T, Murao M, Isoshima T, Kobayashi D, Mitomo H, Ijiro K, Kimura-Suda H. Evaluation method for proteoglycans using near-infrared spectroscopy. ANAL SCI 2025; 41:395-401. [PMID: 39853477 DOI: 10.1007/s44211-025-00715-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2024] [Accepted: 12/19/2024] [Indexed: 01/26/2025]
Abstract
Cartilage is a connective tissue composed of mainly water, collagen (COL) and proteoglycans (PGs) including chondroitin sulfate (CS). Near-infrared (NIR) spectroscopy is adequate for examination of soft and hard tissues with large amount of water non-destructively and non-invasively. We measured tablets containing CS and COL using NIR spectroscopy to develop an evaluation method for PGs in cartilage non-destructively and non-invasively. Calibration curves were constructed using the NIR spectra of the tablets that show the quantitative linear relationship between the concentration and height of the second derivative at 4260 cm-1 for COL and at 5800 cm-1 for COL and CS. An equation to calculate the CS-to-COL ratio was derived from the calibrated slopes at 5800 and 4260 cm-1, and the utility of the equation was demonstrated by the evaluation of tablets. Moreover, we conducted an evaluation of the CS-to-COL ratio in the aqueous nucleus pulposus and annulus fibrosus, and the results were consistent with the glycosaminoglycans (GAGs)-to-COL ratios obtained through Raman spectroscopy of the same specimens. Thus, this method is adequate for evaluating PGs with large amount of water non-destructively, non-invasively and with less damage.
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Affiliation(s)
- Fumiya Nakamura
- Chitose Institute of Science and Technology, Chitose, Hokkaido, 066-8655, Japan
| | - Tomoki Ikemizu
- Chitose Institute of Science and Technology, Chitose, Hokkaido, 066-8655, Japan
| | - Miu Murao
- Chitose Institute of Science and Technology, Chitose, Hokkaido, 066-8655, Japan
| | | | - Daiji Kobayashi
- Chitose Institute of Science and Technology, Chitose, Hokkaido, 066-8655, Japan
| | - Hideyuki Mitomo
- Research Institute for Electronic Science, Hokkaido University, Sapporo, Hokkaido, 001-0021, Japan
| | - Kuniharu Ijiro
- Research Institute for Electronic Science, Hokkaido University, Sapporo, Hokkaido, 001-0021, Japan
| | - Hiromi Kimura-Suda
- Chitose Institute of Science and Technology, Chitose, Hokkaido, 066-8655, Japan.
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Hancu G, Székely-Szentmiklósi B, Stroia DG, Kelemen H. Applications of Capillary Electrophoresis for the Detection of Adulterants in Dietary Supplements. Pharmaceuticals (Basel) 2024; 17:1119. [PMID: 39338284 PMCID: PMC11434824 DOI: 10.3390/ph17091119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 08/20/2024] [Accepted: 08/23/2024] [Indexed: 09/30/2024] Open
Abstract
In recent years, the consumption of dietary supplements, particularly those incorporating plant-based ingredients, has increased greatly, driven by the perception of their natural origins and purported minimal health risks. However, one significant safety concern revolves around the adulteration of dietary supplements, wherein unscrupulous manufacturers may illegally incorporate pharmaceutical substances or their analogs into these products to achieve increased efficiency and bolster sales. This review assesses the role of capillary electrophoresis (CE) in ensuring the quality control of dietary supplement products over the past two decades. This study provides an overview of various applications of CE in analyzing dietary supplements, outlining the typical attributes of natural product analysis using CE. These analyses demonstrate the broad versatility of CE, exemplified by its diverse applications and detection modes. Moreover, the review highlights the growing prominence of CE as a separation technique in quality control, by comparison with more conventional methods like high-performance liquid chromatography (HPLC). Through this exploration, the review elucidates the pivotal role of CE in upholding the integrity and safety of dietary supplements, in connection with a landscape of evolving regulatory challenges and consumer demands.
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Affiliation(s)
- Gabriel Hancu
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, "George Emil Palade" University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, 540142 Târgu Mureș, Romania
| | - Blanka Székely-Szentmiklósi
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, "George Emil Palade" University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, 540142 Târgu Mureș, Romania
| | - Denisa Gabriela Stroia
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, "George Emil Palade" University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, 540142 Târgu Mureș, Romania
| | - Hajnal Kelemen
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, "George Emil Palade" University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, 540142 Târgu Mureș, Romania
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3
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Antia IU, Hills FA, Shah AJ. Disaccharide compositional analysis of chondroitin sulphate using WAX HILIC-MS with pre-column procainamide labelling; application to the placenta in pre-eclampsia. ANALYTICAL METHODS : ADVANCING METHODS AND APPLICATIONS 2024; 16:566-575. [PMID: 38189556 DOI: 10.1039/d3ay01578e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/09/2024]
Abstract
Chondroitin sulphate (CS) and dermatan sulphate are negatively charged linear heteropolysaccharides. These glycosaminoglycans (GAG) are involved in cellular signalling via binding to growth factors. CS is expressed in a range of tissue and biological fluids and is highly expressed in the placenta. There is evidence that decorin; a CS proteoglycan is significantly decreased in pre-eclampsia and fetal growth restriction. It is considered that GAG chain composition may influence cellular processes that are altered in pre-eclampsia. The goal of the present study was to develop an LC-MS method with precolumn procainamide labelling for the disaccharide compositional analysis of CS. The method was used to investigate whether the disaccharide composition of placenta-extracted CS is altered in pre-eclampsia. The study revealed differential disaccharide compositions of placental chondroitin sulphate between pre-eclampsia and other pregnancy conditions. This suggests that the method may have diagnostic potential for pregnancy disorders. Furthermore, the findings suggest that CS sulphation might play a significant role in maternal labour.
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Affiliation(s)
- Imeobong U Antia
- Glycan Research Group, Department of Natural Sciences, Faculty of Science and Technology, Middlesex University, London, UK.
| | - Frank A Hills
- Glycan Research Group, Department of Natural Sciences, Faculty of Science and Technology, Middlesex University, London, UK.
| | - Ajit J Shah
- Glycan Research Group, Department of Natural Sciences, Faculty of Science and Technology, Middlesex University, London, UK.
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4
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Brito R, Costa D, Dias C, Cruz P, Barros P. Chondroitin Sulfate Supplements for Osteoarthritis: A Critical Review. Cureus 2023; 15:e40192. [PMID: 37431333 PMCID: PMC10329866 DOI: 10.7759/cureus.40192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/09/2023] [Indexed: 07/12/2023] Open
Abstract
Over the years, chondroitin sulfate (CS) has been used as a slow-acting drug for the treatment of osteoarthritis, for the reduction of pain and improvement of function, and for its disease-modifying properties by limiting cartilage volume loss and joint space narrowing progression. However, there have been inconsistencies in published trials regarding clinical efficacy, with reports of a lack of significant effects compared to placebo. The therapeutic effects of chondroitin sulfate may depend on many variables, such as the source of origin, purity, and contamination with by-products. Another source of confusion may be related to the fact that CS is commonly combined with glucosamine, which makes it challenging to isolate the specific contribution of chondroitin to the therapeutic outcome. This is aggravated by the fact that CS supplements, used in many countries, are not regulated, and labels wrongly claim high levels of purity. Many of these inferior CS products may have been used in clinical trials, which may have had limited but significant results. This has led to recent recommendations to opt for higher-purity pharmacologic-grade CS for the treatment of OA. This article aims to provide an up-to-date view of the current literature regarding the biological effects and efficacy of CS and discusses the quality of available chondroitin sulfate supplements and the current direction in CS investigation. This review concludes that pharmacologic-grade CS supplements may have clinically significant benefits when properly standardized; however, high-quality evidence from properly designed clinical trials is still needed to draw definitive conclusions about clinical efficacy in osteoarthritis.
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Affiliation(s)
- Rui Brito
- Physical Medicine and Rehabilitation, Centro Hospitalar e Universitário de Santo António, Porto, PRT
| | - Diogo Costa
- Physical Medicine and Rehabilitation, Centro Hospitalar e Universitário de Santo António, Porto, PRT
| | - Carina Dias
- Physical Medicine and Rehabilitation, Centro Hospitalar e Universitário de Santo António, Porto, PRT
| | - Patrícia Cruz
- Physical Medicine and Rehabilitation, Centro Hospitalar e Universitário de Santo António, Porto, PRT
| | - Paula Barros
- Physical Medicine and Rehabilitation, Centro Hospitalar e Universitário de Santo António, Porto, PRT
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Sahu B, Shrama DD, Jayakumar GC, Madhan B, Zameer F. A review on an imperative by-product: Glycosaminoglycans- A Holistic approach. CARBOHYDRATE POLYMER TECHNOLOGIES AND APPLICATIONS 2022. [DOI: 10.1016/j.carpta.2022.100275] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
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Cimini D, Boccella S, Alfano A, Stellavato A, Paino S, Schiraldi C, Guida F, Perrone M, Donniacuo M, Tirino V, Desiderio V, Rinaldi B. Evaluation of unsulfated biotechnological chondroitin in a knee osteoarthritis mouse model as a potential novel functional ingredient in nutraceuticals and pharmaceuticals. Front Bioeng Biotechnol 2022; 10:934997. [PMID: 36466352 PMCID: PMC9714611 DOI: 10.3389/fbioe.2022.934997] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Accepted: 10/28/2022] [Indexed: 10/29/2023] Open
Abstract
Osteoarthritis is a very disabling disease that can be treated with both non-pharmacological and pharmacological approaches. In the last years, pharmaceutical-grade chondroitin sulfate (CS) and glucosamine emerged as symptomatic slow-acting molecules, effective in pain reduction and improved function in patients affected by osteoarthritis. CS is a sulfated glycosaminoglycan that is currently produced mainly by extraction from animal tissues, and it is commercialized as a pharmaceutical-grade ingredient and/or food supplement. However, public concern on animal product derivatives has prompted the search for alternative non-extractive production routes. Thus, different approaches were established to obtain animal-free natural identical CS. On the other hand, the unsulfated chondroitin, which can be obtained via biotechnological processes, demonstrated promising anti-inflammatory properties in vitro, in chondrocytes isolated from osteoarthritic patients. Therefore, the aim of this study was to explore the potential of chondroitin, with respect to the better-known CS, in an in vivo mouse model of knee osteoarthritis. Results indicate that the treatment with biotechnological chondroitin (BC), similarly to CS, significantly reduced the severity of mechanical allodynia in an MIA-induced osteoarthritic mouse model. Decreased cartilage damage and a reduction of inflammation- and pain-related biochemical markers were also observed. Overall, our data support a beneficial activity of biotechnological unsulfated chondroitin in the osteoarthritis model tested, thus suggesting BC as a potential functional ingredient in pharmaceuticals and nutraceuticals with the advantage of avoiding animal tissue extraction.
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Affiliation(s)
- Donatella Cimini
- Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania L. Vanvitelli, Naples, Italy
| | - Serena Boccella
- Department of Experimental Medicine, Section of Biotechnology, Medical Histology and Molecular Biology Naples, University of Campania L. Vanvitelli, Naples, Italy
| | - Alberto Alfano
- Department of Experimental Medicine, Section of Biotechnology, Medical Histology and Molecular Biology Naples, University of Campania L. Vanvitelli, Naples, Italy
| | - Antonietta Stellavato
- Department of Experimental Medicine, Section of Biotechnology, Medical Histology and Molecular Biology Naples, University of Campania L. Vanvitelli, Naples, Italy
| | - Salvatore Paino
- Department of Experimental Medicine, Section of Biotechnology, Medical Histology and Molecular Biology Naples, University of Campania L. Vanvitelli, Naples, Italy
| | - Chiara Schiraldi
- Department of Experimental Medicine, Section of Biotechnology, Medical Histology and Molecular Biology Naples, University of Campania L. Vanvitelli, Naples, Italy
| | - Francesca Guida
- Department of Experimental Medicine, Section of Biotechnology, Medical Histology and Molecular Biology Naples, University of Campania L. Vanvitelli, Naples, Italy
| | - Michela Perrone
- Department of Experimental Medicine, Section of Biotechnology, Medical Histology and Molecular Biology Naples, University of Campania L. Vanvitelli, Naples, Italy
| | - Maria Donniacuo
- Department of Experimental Medicine, Section of Biotechnology, Medical Histology and Molecular Biology Naples, University of Campania L. Vanvitelli, Naples, Italy
| | - Virginia Tirino
- Department of Experimental Medicine, Section of Biotechnology, Medical Histology and Molecular Biology Naples, University of Campania L. Vanvitelli, Naples, Italy
| | - Vincenzo Desiderio
- Department of Experimental Medicine, Section of Biotechnology, Medical Histology and Molecular Biology Naples, University of Campania L. Vanvitelli, Naples, Italy
| | - Barbara Rinaldi
- Department of Experimental Medicine, Section of Biotechnology, Medical Histology and Molecular Biology Naples, University of Campania L. Vanvitelli, Naples, Italy
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Hyaluronic acid and chondroitin sulfate (meth)acrylate-based hydrogels for tissue engineering: Synthesis, characteristics and pre-clinical evaluation. Biomaterials 2020; 268:120602. [PMID: 33360302 DOI: 10.1016/j.biomaterials.2020.120602] [Citation(s) in RCA: 88] [Impact Index Per Article: 17.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Revised: 12/09/2020] [Accepted: 12/10/2020] [Indexed: 12/20/2022]
Abstract
Hydrogels based on photocrosslinkable Hyaluronic Acid Methacrylate (HAMA) and Chondroitin Sulfate Methacrylate (CSMA) are presently under investigation for tissue engineering applications. HAMA and CSMA gels offer tunable characteristics such as tailorable mechanical properties, swelling characteristics, and enzymatic degradability. This review gives an overview of the scientific literature published regarding the pre-clinical development of covalently crosslinked hydrogels that (partially) are based on HAMA and/or CSMA. Throughout the review, recommendations for the next steps in clinical translation of hydrogels based on HAMA or CSMA are made and potential pitfalls are defined. Specifically, a myriad of different synthetic routes to obtain polymerizable hyaluronic acid and chondroitin sulfate derivatives are described. The effects of important parameters such as degree of (meth)acrylation and molecular weight of the synthesized polymers on the formed hydrogels are discussed and useful analytical techniques for their characterization are summarized. Furthermore, the characteristics of the formed hydrogels including their enzymatic degradability are discussed. Finally, a summary of several recent applications of these hydrogels in applied fields such as cartilage and cardiac regeneration and advanced tissue modelling is presented.
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Volpi N, Galeotti F, Maccari F, Capitani F, Mantovani V. Structural definition of terrestrial chondroitin sulfate of various origin and repeatability of the production process. J Pharm Biomed Anal 2020; 195:113826. [PMID: 33358299 DOI: 10.1016/j.jpba.2020.113826] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Revised: 12/02/2020] [Accepted: 12/03/2020] [Indexed: 10/22/2022]
Abstract
We report results on the structure, physicochemical characteristics and purity of chondroitin sulfate (CS) samples derived from three largely available and common biological sources such as bovine and porcine trachea and chicken keel bones with the aim to define their structural signatures. Many lots of CS produced by a manufacturer at industrial scale were characterized with a view to assess the reproducibility of the process as not controlled extractive procedures may produce final products with variable structure and biological contaminants as well as not constant clinical efficacy and safety. By using standardized source animal tissues and manufacturing procedure, highly pure CS (∼92 %) products with constant structure and characteristics were obtained. Bovine CS showed a lower molecular weight (MWw of ∼21,500 Da) than porcine (MWw of ∼26,000 Da) and chicken (MWw of ∼35,900 Da) products with a CV% of ∼2.0-7.5 and a polydispersity variability of 0.7-2.7 %. The ratio between the sulfate groups main located in position 4 and 6 of N-acetyl-galactosamine (4/6 ratio) was ∼1.70 for bovine CS versus a value of 3.60 for porcine and ∼2.70 for chicken samples with a overall charge density of 0.92-0.93 and a CV% of 2.1-2.5. The final products also showed the presence of a very low and constant content of other co-purified bio(macro)molecules (hyaluronic acid, keratan sulfate, dermatan sulfate, heparan sulfate, nucleic acids and proteins), calcium and sodium, and the absence of versican. Finally, a high reproducibility of molecular weight values, disaccharide composition, specific optical rotation and particle dimension was observed. The observed parameters are structural signatures useful to specifically identify the origin of CS and obtained by a standardized and highly reproducible manufacturing process. The compositional profile determined from this study provides a measure of the norm and range of variation in CS samples of terrestrial origin produced under standardized production protocol to which future pharmaceutical/nutraceutical final products can be compared. Moreover, the physicochemical properties including molecular weight, disaccharide composition, presence of natural contaminants and particle dimension were characterized to provide the basis of CS of high quality for application as pharmaceutical/nutraceutical active agents.
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Affiliation(s)
- Nicola Volpi
- Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
| | - Fabio Galeotti
- Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Francesca Maccari
- Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Federica Capitani
- Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Veronica Mantovani
- Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy; Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy
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9
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Restaino OF, De Rosa M, Schiraldi C. High-performance capillary electrophoresis to determine intact keratan sulfate and hyaluronic acid in animal origin chondroitin sulfate samples and food supplements. Electrophoresis 2020; 41:1740-1748. [PMID: 32357264 DOI: 10.1002/elps.202000028] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2020] [Revised: 03/28/2020] [Accepted: 04/17/2020] [Indexed: 11/09/2022]
Abstract
Chondroitin sulfate is extracted from animal cartilaginous tissues and is commercialized as active principle against osteoarthritis. Its biological activity depends on its purity grade and could be altered by the presence of other glycosaminoglycans like keratan sulfate that could be contemporarily extracted from animal tissues or like hyaluronic acid that, instead, is added on purpose in food supplements. Although numerous methods are reported in literature for quality control analyses of chondroitin sulfate, few of them are able to detect other glycosaminoglycans. In this paper, for the first time, a new high-performance CE method was set up to quantify the chondroitin sulfate, the eventual keratan sulfate, and hyaluronic acid as intact chains: five chondroitin sulfate standards and 13 animal origin samples or food supplements from six different suppliers were analyzed. The new method was able to determine keratan sulfate similarly to a previously reported high-performance anion-exchange chromatography method, but in addition it showed the advantage to determine also the hyaluronic acid as never reported before.
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Affiliation(s)
- Odile Francesca Restaino
- Department of Experimental Medicine, Section of Biotechnology and Molecular Biology, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Mario De Rosa
- Department of Experimental Medicine, Section of Biotechnology and Molecular Biology, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Chiara Schiraldi
- Department of Experimental Medicine, Section of Biotechnology and Molecular Biology, University of Campania "Luigi Vanvitelli", Naples, Italy
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Chondroitin Sulfate Safety and Quality. Molecules 2019; 24:molecules24081447. [PMID: 31013685 PMCID: PMC6515237 DOI: 10.3390/molecules24081447] [Citation(s) in RCA: 81] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2019] [Revised: 04/08/2019] [Accepted: 04/09/2019] [Indexed: 12/31/2022] Open
Abstract
The industrial production of chondroitin sulfate (CS) uses animal tissue sources as raw material derived from different terrestrial or marine species of animals. CS possesses a heterogeneous structure and physical-chemical profile in different species and tissues, responsible for the various and more specialized functions of these macromolecules. Moreover, mixes of different animal tissues and sources are possible, producing a CS final product having varied characteristics and not well identified profile, influencing oral absorption and activity. Finally, different extraction and purification processes may introduce further modifications of the CS structural characteristics and properties and may lead to extracts having a variable grade of purity, limited biological effects, presence of contaminants causing problems of safety and reproducibility along with not surely identified origin. These aspects pose a serious problem for the final consumers of the pharmaceutical or nutraceutical products mainly related to the traceability of CS and to the declaration of the real origin of the active ingredient and its content. In this review, specific, sensitive and validated analytical quality controls such as electrophoresis, eHPLC (enzymatic HPLC) and HPSEC (high-performance size-exclusion chromatography) able to assure CS quality and origin are illustrated and discussed.
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Kastana P, Choleva E, Poimenidi E, Karamanos N, Sugahara K, Papadimitriou E. Insight into the role of chondroitin sulfate E in angiogenesis. FEBS J 2019; 286:2921-2936. [DOI: 10.1111/febs.14830] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2018] [Revised: 02/05/2019] [Accepted: 03/29/2019] [Indexed: 12/11/2022]
Affiliation(s)
- Pinelopi Kastana
- Laboratory of Molecular Pharmacology Department of Pharmacy University of Patras Greece
| | - Effrosyni Choleva
- Laboratory of Molecular Pharmacology Department of Pharmacy University of Patras Greece
| | - Evangelia Poimenidi
- Laboratory of Molecular Pharmacology Department of Pharmacy University of Patras Greece
| | - Nikos Karamanos
- Biochemistry, Biochemical Analysis and Matrix Pathobiology Res. Group Laboratory of Biochemistry Department of Chemistry University of Patras Greece
| | - Kazuyuki Sugahara
- Faculty of Pharmacy Department of Pathobiochemistry Meijo University Nagoya Japan
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Ndeh D, Munoz Munoz J, Cartmell A, Bulmer D, Wills C, Henrissat B, Gray J. The human gut microbe Bacteroides thetaiotaomicron encodes the founding member of a novel glycosaminoglycan-degrading polysaccharide lyase family PL29. J Biol Chem 2018; 293:17906-17916. [PMID: 30262663 DOI: 10.1074/jbc.ra118.004510] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2018] [Revised: 09/24/2018] [Indexed: 12/16/2022] Open
Abstract
Glycosaminoglycans (GAGs) and GAG-degrading enzymes have wide-ranging applications in the medical and biotechnological industries. The former are also an important nutrient source for select species of the human gut microbiota (HGM), a key player in host-microbial interactions. How GAGs are metabolized by the HGM is therefore of interest and has been extensively investigated in the model human gut microbe Bacteroides thetaiotaomicron. The presence of as-yet uncharacterized GAG-inducible genes in its genome and of related species, however, is testament to our incomplete understanding of this process. Nevertheless, it presents a potential opportunity for the discovery of additional GAG-degrading enzymes. Here, we investigated a gene of unknown function (BT_3328) from the chondroitin sulfate (CS) utilization locus of B. thetaiotaomicron NMR and UV spectroscopic assays revealed that it encodes a novel polysaccharide lyase (PL), hereafter referred to as BtCDH, reflecting its source (B. thetaiotaomicron (Bt)) and its ability to degrade the GAGs CS, dermatan sulfate (DS), and hyaluronic acid (HA). When incubated with HA, BtCDH generated a series of unsaturated HA sugars, including Δ4,5UA-GlcNAc, Δ4,5UA-GlcNAc-GlcA-GlcNac, Δ4,5UA-[GlcNAc-GlcA]2-GlcNac, and Δ4,5UA-[GlcNAc-GlcA]3-GlcNac, as end products and hence was classed as endo-acting. A combination of genetic and biochemical assays revealed that BtCDH localizes to the cell surface of B. thetaiotaomicron where it enables extracellular GAG degradation. BtCDH homologs were also detected in several other HGM species, and we therefore propose that it represents the founding member of a new polysaccharide lyase family (PL29). The current discovery also contributes new insights into CS metabolism by the HGM.
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Affiliation(s)
- Didier Ndeh
- From the Institute for Cell and Molecular Biosciences, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, United Kingdom.
| | - Jose Munoz Munoz
- Department of Applied Sciences, Northumbria University, Newcastle upon Tyne, NE1 8ST, United Kingdom
| | - Alan Cartmell
- From the Institute for Cell and Molecular Biosciences, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, United Kingdom
| | - David Bulmer
- From the Institute for Cell and Molecular Biosciences, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, United Kingdom; Bio-Imaging Unit, William Leech Building, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, United Kingdom
| | - Corinne Wills
- School of Natural and Environmental Sciences, Bedson Building, King's Road, Newcastle upon Tyne NE1 7RU, United Kingdom
| | - Bernard Henrissat
- Architecture et Fonction des Macromolécules Biologiques, CNRS, Aix-Marseille University, F-13288 Marseille, France; USC1408 Architecture et Fonction des Macromolécules Biologiques, Institut National de la Recherche Agronomique, F-13288 Marseille, France; Department of Biological Sciences, King Abdulaziz University, 23218 Jeddah, Saudi Arabia
| | - Joseph Gray
- From the Institute for Cell and Molecular Biosciences, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, United Kingdom
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Bougatef H, Krichen F, Capitani F, Amor IB, Maccari F, Mantovani V, Galeotti F, Volpi N, Bougatef A, Sila A. Chondroitin sulfate/dermatan sulfate from corb (Sciaena umbra) skin: Purification, structural analysis and anticoagulant effect. Carbohydr Polym 2018; 196:272-278. [DOI: 10.1016/j.carbpol.2018.05.019] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2018] [Revised: 04/18/2018] [Accepted: 05/06/2018] [Indexed: 01/17/2023]
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14
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Rocco A, Donati E, Touloupakis E, Aturki Z. Miniaturized separation techniques as analytical methods to ensure quality and safety of dietary supplements. Trends Analyt Chem 2018. [DOI: 10.1016/j.trac.2018.04.004] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Vasiliadis HS, Tsikopoulos K. Glucosamine and chondroitin for the treatment of osteoarthritis. World J Orthop 2017; 8:1-11. [PMID: 28144573 PMCID: PMC5241539 DOI: 10.5312/wjo.v8.i1.1] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2016] [Revised: 09/19/2016] [Accepted: 10/17/2016] [Indexed: 02/06/2023] Open
Abstract
The prevalence of primary or idiopathic osteoarthritis (OA) of knee and hip joints has substantially increased in general population during the last decades. Analgesics and non-steroidal anti-inflammatory drugs are currently extensively used as non-surgical treatment options. However, they act as symptomatic treatments, not offering a cure of OA and they are accused for an increased risk of adverse events. Glucosamine (GL) and chondroitin (CH) are nutritional supplements that have recently gained widespread use as treatment options for OA. They potentially or theoretically act as chondroprotectors or/and as "disease-modifying OA drugs" offering not only symptomatic relief but also alteration of the natural history of OA. However, although many studies have showed a significant treatment effect, accompanied with remarkable safety, there is still controversy regarding their relative effectiveness compared with placebo or other treatments. The scope of this review is to present and critically evaluate the current evidence-based information regarding the administration of GL and CH for the treatment of knee or hip OA. Our focus is to investigate the clinical efficacy and safety after the use of these supplements. An effect of GL and CH on both clinical and radiological findings has been shown. However, only a few high-quality level I trials exist in the literature, especially on the assessment of radiological progression of OA. The effect sizes are generally small and probably not clinically relevant. Even the validity of these results is limited by the high risk of bias introduced in the studies. Both GL and CH seem to be safe with no serious adverse events reported. There is currently no convincing information for the efficacy of GL and CH on OA.
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16
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van Gemst JJ, Loeven MA, de Graaf MJJ, Berden JHM, Rabelink TJ, Smit CH, van der Vlag J. RNA Contaminates Glycosaminoglycans Extracted from Cells and Tissues. PLoS One 2016; 11:e0167336. [PMID: 27898729 PMCID: PMC5127559 DOI: 10.1371/journal.pone.0167336] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2016] [Accepted: 11/11/2016] [Indexed: 12/27/2022] Open
Abstract
Glycosaminoglycans (GAGs) are linear negatively charged polysaccharides and important components of extracellular matrices and cell surface glycan layers such as the endothelial glycocalyx. The GAG family includes sulfated heparin, heparan sulfate (HS), dermatan sulfate (DS), chondroitin sulfate (CS), keratan sulfate, and non-sulfated hyaluronan. Because relative expression of GAGs is dependent on cell-type and niche, isolating GAGs from cell cultures and tissues may provide insight into cell- and tissue-specific GAG structure and functions. In our objective to obtain structural information about the GAGs expressed on a specialized mouse glomerular endothelial cell culture (mGEnC-1) we adapted a recently published GAG isolation protocol, based on cell lysis, proteinase K and DNase I digestion. Analysis of the GAGs contributing to the mGEnC-1 glycocalyx indicated a large HS and a minor CS content on barium acetate gel. However, isolated GAGs appeared resistant to enzymatic digestion by heparinases. We found that these GAG extracts were heavily contaminated with RNA, which co-migrated with HS in barium acetate gel electrophoresis and interfered with 1,9-dimethylmethylene blue (DMMB) assays, resulting in an overestimation of GAG yields. We hypothesized that RNA may be contaminating GAG extracts from other cell cultures and possibly tissue, and therefore investigated potential RNA contaminations in GAG extracts from two additional cell lines, human umbilical vein endothelial cells and retinal pigmental epithelial cells, and mouse kidney, liver, spleen and heart tissue. GAG extracts from all examined cell lines and tissues contained varying amounts of contaminating RNA, which interfered with GAG quantification using DMMB assays and characterization of GAGs by barium acetate gel electrophoresis. We therefore recommend routinely evaluating the RNA content of GAG extracts and propose a robust protocol for GAG isolation that includes an RNA digestion step.
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Affiliation(s)
- Jasper J. van Gemst
- Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands
| | - Markus A. Loeven
- Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands
| | - Mark J. J. de Graaf
- Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands
| | - Jo H. M. Berden
- Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands
| | - Ton J. Rabelink
- Department of Nephrology and Einthoven Laboratory for Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - Cornelis H. Smit
- Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands
| | - Johan van der Vlag
- Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands
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Petridis T, Giannakopoulou D, Stamatopoulou V, Grafanaki K, Kostopoulos CG, Papadaki H, Malavaki CJ, Karamanos NK, Douroumi S, Papachristou D, Magoulas GE, Papaioannou D, Drainas D. Investigation on Toxicity and Teratogenicity in Rats of a Retinoid-Polyamine Conjugate with Potent Anti-Inflammatory Properties. ACTA ACUST UNITED AC 2016; 107:32-44. [PMID: 26762583 DOI: 10.1002/bdrb.21170] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2015] [Accepted: 12/08/2015] [Indexed: 11/07/2022]
Abstract
Previous studies have shown that N(1),N(12)-bis(all-trans-retinoyl)spermine (RASP), a retinoid analog, inhibits RNase P activity and angiogenesis in the chicken embryo chorioallantoic membrane, demonstrates anti-tumor activity on prostate cancer cells, and acts as anti-inflammatory agent, being more effective and less toxic than all-trans retinoic acid. In an attempt to further characterize the biological profile of RASP, we tested its effects on organ toxicity and teratogenicity by daily oral gavage of RASP at a level of 50 mg/Kg of body weight in two generations of rats. We found that this compound does not induce changes to the body growth, the appearance of physical features, and the animal's reflexes. Additionally, no substantial histopathological lesions were found in brain, heart, lung, thymus, liver, thyroid gland, adrenal gland, pituitary gland, kidneys, spleen, skin, femora, prostate, testis, epididymis, vagina, uterus, and ovaries of RASP-treated animals. These results suggest RASP, as a promising lead compound for the treatment of several dermatological disorders and certain cancer types, has apparently minimal toxic side-effects as revealed in this two-generation reproduction study in rats.
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Affiliation(s)
- Theodoros Petridis
- Department of Biochemistry, School of Medicine, University of Patras, Patras, Greece
| | | | | | - Katerina Grafanaki
- Department of Biochemistry, School of Medicine, University of Patras, Patras, Greece
| | | | - Helen Papadaki
- Department of Anatomy, School of Medicine, University of Patras, Patras, Greece
| | - Christina J Malavaki
- Laboratory of Biochemistry, Department of Chemistry, School of Natural Sciences, University of Patras, Patras, Greece
| | - Nikos K Karamanos
- Laboratory of Biochemistry, Department of Chemistry, School of Natural Sciences, University of Patras, Patras, Greece
| | - Stathianna Douroumi
- Department of Pharmacology, School of Medicine, University of Patras, Patras, Greece
| | - Dionysios Papachristou
- Department of Anatomy, Ηistology and Embryology, School of Medicine, University of Patras, Patras, Greece
| | - George E Magoulas
- Department of Chemistry, School of Natural Sciences, University of Patras, Patras, Greece
| | - Dionissios Papaioannou
- Department of Chemistry, School of Natural Sciences, University of Patras, Patras, Greece
| | - Denis Drainas
- Department of Biochemistry, School of Medicine, University of Patras, Patras, Greece
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18
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Zhao T, Song X, Tan X, Xu L, Yu M, Wang S, Liu X, Wang F. Development of a rapid method for simultaneous separation of hyaluronic acid, chondroitin sulfate, dermatan sulfate and heparin by capillary electrophoresis. Carbohydr Polym 2016; 141:197-203. [PMID: 26877013 DOI: 10.1016/j.carbpol.2016.01.016] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2015] [Revised: 01/05/2016] [Accepted: 01/09/2016] [Indexed: 01/04/2023]
Abstract
This study reports the use of diethylenetriamine as background electrolyte for the simultaneous separation of hyaluronan acid, chondroitin sulfate, dermatan sulfate and heparin. The analytes were baseline separated by using an uncoated fused silica capillary at 37°C with a run time of 23min. The migration order, with hyaluronan acid at first and heparin at last, was related to the sulfation degree. The effect of salt concentration on resolution and migration order was also investigated. The developed method was applied to the simultaneous determination of hyaluronan acid and chondroitin sulfate in mouse plasma. Interferences in plasma were removed by protein precipitation and glycosaminoglycans were further purified by ethanol precipitation. The method was validated over the concentration range from 50 to 600μg/mL for hyaluronan acid and 500 to 6000μg/mL for chondroitin sulfate in mouse plasma. Results from assay validations showed that the method was selective and robust.
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Affiliation(s)
- Ting Zhao
- School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China
| | - Xinlei Song
- School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China
| | - Xiaoqing Tan
- School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China
| | - Linghua Xu
- School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China
| | - Mingxiu Yu
- School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China
| | - Siyi Wang
- School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China
| | - Xiumei Liu
- School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
| | - Fengshan Wang
- School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China; Shandong Provincial Key Laboratory of Carbohydrate Chemistry and Glycobiology, Jinan 250012, China.
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19
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Park KY, Kim DY, Shin WS. Roles of chondroitin sulfate in oil-in-water emulsions formulated using bovine serum albumin. Food Sci Biotechnol 2015. [DOI: 10.1007/s10068-015-0204-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
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20
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Blanco M, Fraguas J, Sotelo CG, Pérez-Martín RI, Vázquez JA. Production of Chondroitin Sulphate from Head, Skeleton and Fins of Scyliorhinus canicula By-Products by Combination of Enzymatic, Chemical Precipitation and Ultrafiltration Methodologies. Mar Drugs 2015; 13:3287-308. [PMID: 26023837 PMCID: PMC4483629 DOI: 10.3390/md13063287] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2015] [Accepted: 05/13/2015] [Indexed: 11/24/2022] Open
Abstract
This study illustrates the optimisation of the experimental conditions of three sequential steps for chondroitin sulphate (CS) recovery from three cartilaginous materials of Scyliorhinus canicula by-products. Optimum conditions of temperature and pH were first obtained for alcalase proteolysis of head cartilage (58 °C/pH 8.5/0.1% (v/w)/10 h of hydrolysis). Then, similar optimal conditions were observed for skeletons and fin materials. Enzymatic hydrolysates were subsequently treated with a combination of alkaline hydroalcoholic saline solutions in order to improve the protein hydrolysis and the selective precipitation of CS. Ranges of 0.53–0.64 M (NaOH) and 1.14–1.20 volumes (EtOH) were the levels for optimal chemical treatment depending on the cartilage origin. Finally, selective purification and concentration of CS and protein elimination of samples obtained from chemical treatment, was assessed by a combination of ultrafiltration and diafiltration (UF-DF) techniques at 30 kDa.
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Affiliation(s)
- María Blanco
- Marine Research Institute (IIM-CSIC), Eduardo Cabello, 6. Vigo, Galicia 36208, Spain.
| | - Javier Fraguas
- Marine Research Institute (IIM-CSIC), Eduardo Cabello, 6. Vigo, Galicia 36208, Spain.
| | - Carmen G Sotelo
- Marine Research Institute (IIM-CSIC), Eduardo Cabello, 6. Vigo, Galicia 36208, Spain.
| | | | - José Antonio Vázquez
- Marine Research Institute (IIM-CSIC), Eduardo Cabello, 6. Vigo, Galicia 36208, Spain.
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21
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Discrepancies in composition and biological effects of different formulations of chondroitin sulfate. Molecules 2015; 20:4277-89. [PMID: 25756648 PMCID: PMC6272499 DOI: 10.3390/molecules20034277] [Citation(s) in RCA: 72] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2015] [Revised: 02/25/2015] [Accepted: 02/26/2015] [Indexed: 01/16/2023] Open
Abstract
Osteoarthritis is a common, progressive joint disease, and treatments generally aim for symptomatic improvement. However, SYmptomatic Slow-Acting Drugs in Osteoarthritis (SYSADOAs) not only reduce joint pain, but slow structural disease progression. One such agent is chondroitin sulfate—a complex, heterogeneous polysaccharide. It is extracted from various animal cartilages, thus has a wide range of molecular weights and different amounts and patterns of sulfation. Chondroitin sulfate has an excellent safety profile, and although various meta-analyses have concluded that it has a beneficial effect on symptoms and structure, others have concluded little or no benefit. This may be due, at least partly, to variations in the quality of the chondroitin sulfate used for a particular study. Chondroitin sulfate is available as pharmaceutical- and nutraceutical-grade products, and the latter have great variations in preparation, composition, purity and effects. Moreover, some products contain a negligible amount of chondroitin sulfate and among samples with reasonable amounts, in vitro testing showed widely varying effects. Of importance, although some showed anti-inflammatory effects, others demonstrated weak effects, and some instances were even pro-inflammatory. This could be related to contaminants, which depend on the origin, production and purification process. It is therefore vitally important that only pharmaceutical-grade chondroitin sulfate be used for treating osteoarthritis patients.
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22
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Zhao T, Zhou G, Wu Y, Liu X, Wang F. Gold nanomaterials based pseudostationary phases in capillary electrophoresis: a brand-new attempt at chondroitin sulfate isomers separation. Electrophoresis 2015; 36:588-95. [PMID: 25395164 DOI: 10.1002/elps.201400440] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2014] [Revised: 10/19/2014] [Accepted: 10/29/2014] [Indexed: 11/07/2022]
Abstract
In this work, a CE method with bare gold nanorods (GNRs) based pseudostationary phase was developed and applied for the separation of chondroitin sulfate (CS) isomers, CS, and dermatan sulfate (DS). The separation efficiency was investigated by varying the experimental parameters such as concentration and pH of the BGE, separation voltage, internal diameter of capillary, different size, and morphology of gold nanomaterials. Results showed that different size and morphology of gold nanomaterials had different effects on the separation of CS and DS. The best separation of CS and DS was achieved in the BGE composed of aqueous 150 mmol/L (mM) ethylenediamine + 20 mM sodium dihydrogen phosphate + 30% v/v GNRs, pH 4.5, at the separation voltage of -10 kV. Capillary was 59.2 cm in length (effective length 49 cm), 50 μm id capillary thermostated at 25°C. CE with bare GNRs used as pseudostationary phase was shown to be a suitable technique for the separation of CS and DS mixtures with wider peaks. RSD of migration time and peak area of CS and DS were 0.13, 0.14 and 0.86, 1.07%, respectively.
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Affiliation(s)
- Ting Zhao
- School of Pharmaceutical Sciences, Shandong University, Jinan, China
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23
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Asimakopoulou AP, Malavaki C, Afratis NA, Theocharis AD, Lamari FN, Karamanos NK. Validated capillary electrophoretic assays for disaccharide composition analysis of galactosaminoglycans in biologic samples and drugs/nutraceuticals. Methods Mol Biol 2015; 1229:129-141. [PMID: 25325950 DOI: 10.1007/978-1-4939-1714-3_13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/04/2023]
Abstract
Capillary electrophoresis is a separation technique with high resolving power and sensitivity with applications in glycosaminoglycan analysis. In this chapter, we present validated protocols for determining the variously sulfated chondroitin or dermatan sulfate-derived disaccharides. These approaches involve degradation of the polysaccharides with specific chondro/dermato-lyases and electrophoretic analysis with capillary zone electrophoresis in a low pH operating buffer and reversed polarity. This methodology has been applied to drug/nutraceutical formulations or to biologic samples (blood serum, lens capsule) and has been validated. Analysis of biologic tissue samples is often more demanding in terms of detection sensitivity, and thus concentration pretreatment steps and/or a derivatization step with 2-aminoacridone are often advisable.
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Affiliation(s)
- Athanasia P Asimakopoulou
- Laboratory of Biochemistry, Department of Chemistry, University of Patras, 1414, 26504, Patras, Greece
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24
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Zhao T, Zhang J, Liu X, Wang F. Analysis of chondroitin sulfate from different sources of cartilage by electrophoretically mediated microanalysis. RSC Adv 2015. [DOI: 10.1039/c5ra05576h] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
An electrophoretically mediated microanalysis protocol for the determination of different chondroitin sulfate origins was developed.
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Affiliation(s)
- Ting Zhao
- School of Pharmaceutical Sciences
- Shandong University
- Jinan 250012
- China
| | - Jinfu Zhang
- School of Pharmaceutical Sciences
- Shandong University
- Jinan 250012
- China
| | - Xiumei Liu
- School of Pharmaceutical Sciences
- Shandong University
- Jinan 250012
- China
| | - Fengshan Wang
- School of Pharmaceutical Sciences
- Shandong University
- Jinan 250012
- China
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25
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Baydemir G. Molecularly imprinted cryogels for chondroitin sulfate recognition. ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY 2014; 44:610-7. [PMID: 25353262 DOI: 10.3109/21691401.2014.975236] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Chondroitin sulfate (Cs)-imprinted poly(hydroxyethyl methacrylate)-based macroporous cryogels (CsMIP) were prepared for selective recognition of Cs from an aqueous solution. The selective binding sites for Cs were maintained using vinyl imidazole-Cu(2+) functional groups, during the precomplexation step in the polymerization procedure. Newly synthesized CsMIP cryogel columns were characterized. The separation of Cs from aqueous solutions was studied, both in the continuous system and in the fast protein liquid chromatography (FPLC) system. According to the FPLC studies, the Rs value obtained was 14.72, which shows that the CsMIP cryogel column can successfully separate Cs from aqueous solutions of Cs in the presence of competitor molecules.
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Affiliation(s)
- Gözde Baydemir
- a Division of Biochemistry, Department of Chemistry , Aksaray University , Aksaray , Turkey
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26
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Abstract
SIGNIFICANCE Inflammatory diseases (such as arthritis) of the extracellular matrix (ECM) are of considerable socioeconomic significance. There is clear evidence that reactive oxygen species (ROS) and nitrogen species released by, for instance, neutrophils contribute to the degradation of the ECM. Here we will focus on the ROS-induced degradation of the glycosaminoglycans, one important component of the ECM. RECENT ADVANCES The recently developed "anti-TNF-α" therapy is primarily directed against neutrophilic granulocytes that are powerful sources of ROS. Therefore, a more detailed look into the mechanisms of the reactions of these ROS is reasonable. CRITICAL ISSUES Since both enzymes and ROS contribute to the pathogenesis of inflammatory diseases, it is very difficult to estimate the contributions of the individual species in a complex biological environment. This particularly applies as many products are not stable but only transient products that decompose in a time-dependent manner. Thus, the development of suitable analytical methods as well as the establishment of useful biomarkers is a challenging aspect. FUTURE DIRECTIONS If the mechanisms of ECM destruction are understood in more detail, then the development of suitable drugs to treat inflammatory diseases will be hopefully much more successful.
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Affiliation(s)
- Beate Fuchs
- Medical Department, Institute of Medical Physics and Biophysics, University of Leipzig , Leipzig, Germany
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27
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FACE analysis as a fast and reliable methodology to monitor the sulfation and total amount of chondroitin sulfate in biological samples of clinical importance. Molecules 2014; 19:7959-80. [PMID: 24927366 PMCID: PMC6271866 DOI: 10.3390/molecules19067959] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2014] [Revised: 05/23/2014] [Accepted: 05/27/2014] [Indexed: 01/11/2023] Open
Abstract
Glycosaminoglycans (GAGs) due to their hydrophilic character and high anionic charge densities play important roles in various (patho)physiological processes. The identification and quantification of GAGs in biological samples and tissues could be useful prognostic and diagnostic tools in pathological conditions. Despite the noteworthy progress in the development of sensitive and accurate methodologies for the determination of GAGs, there is a significant lack in methodologies regarding sample preparation and reliable fast analysis methods enabling the simultaneous analysis of several biological samples. In this report, developed protocols for the isolation of GAGs in biological samples were applied to analyze various sulfated chondroitin sulfate- and hyaluronan-derived disaccharides using fluorophore-assisted carbohydrate electrophoresis (FACE). Applications to biologic samples of clinical importance include blood serum, lens capsule tissue and urine. The sample preparation protocol followed by FACE analysis allows quantification with an optimal linearity over the concentration range 1.0–220.0 µg/mL, affording a limit of quantitation of 50 ng of disaccharides. Validation of FACE results was performed by capillary electrophoresis and high performance liquid chromatography techniques.
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Volpi N, Galeotti F, Yang B, Linhardt RJ. Analysis of glycosaminoglycan-derived, precolumn, 2-aminoacridone–labeled disaccharides with LC-fluorescence and LC-MS detection. Nat Protoc 2014; 9:541-58. [DOI: 10.1038/nprot.2014.026] [Citation(s) in RCA: 97] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
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29
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Bauerova K, Ponist S, Kuncirova V, Drafi F, Mihalova D, Paulovicova E, Volpi N. Effect of Nonanimal High- and Low-Molecular-Mass Chondroitin Sulfates Produced by a Biotechnological Process in an Animal Model of Polyarthritis. Pharmacology 2014; 94:109-14. [DOI: 10.1159/000366285] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2014] [Accepted: 07/30/2014] [Indexed: 11/19/2022]
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Henrotin Y, Mathy M, Sanchez C, Lambert C. Chondroitin sulfate in the treatment of osteoarthritis: from in vitro studies to clinical recommendations. Ther Adv Musculoskelet Dis 2012; 2:335-48. [PMID: 22870459 DOI: 10.1177/1759720x10383076] [Citation(s) in RCA: 108] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Chondroitin sulfate (CS) is recommended as a therapeutic intervention in the multimodal approach of osteoarthritis (OA) management. CS has been studied extensively to describe its pharmacology (pharmacokinetic, in vitro and in vivo effects) and its clinical efficacy. Various results have been reported depending on the system of evaluation (model, dosage and duration) and the source of CS (origin and quality). The purpose of this review was to gather most of the available information about CS and to discuss its potency in OA management.
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Affiliation(s)
- Yves Henrotin
- Bone and Cartilage Research Unit, Institute of Pathology, level 5, CHU Sart-Tilman, 4000 Liège, Belgium
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32
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Effect of 12 months treatment with chondroitin sulfate on cartilage volume in knee osteoarthritis patients: a randomized, double-blind, placebo-controlled pilot study using MRI. Clin Rheumatol 2012; 31:1347-57. [DOI: 10.1007/s10067-012-2022-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2011] [Revised: 05/21/2012] [Accepted: 06/04/2012] [Indexed: 02/04/2023]
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33
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Kouvidi K, Berdiaki A, Nikitovic D, Katonis P, Afratis N, Hascall VC, Karamanos NK, Tzanakakis GN. Role of receptor for hyaluronic acid-mediated motility (RHAMM) in low molecular weight hyaluronan (LMWHA)-mediated fibrosarcoma cell adhesion. J Biol Chem 2011; 286:38509-38520. [PMID: 21914806 DOI: 10.1074/jbc.m111.275875] [Citation(s) in RCA: 107] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Hyaluronan (HA) modulates key cancer cell functions through interaction with its CD44 and receptor for hyaluronic acid-mediated motility (RHAMM) receptors. HA was recently found to regulate the migration of fibrosarcoma cells in a manner specifically dependent on its size. Here, we investigated the effect of HA/RHAMM signaling on the ability of HT1080 fibrosarcoma cells to adhere onto fibronectin. Low molecular weight HA (LMWHA) significantly increased (p ≤ 0.01) the adhesion capacity of HT1080 cells, which high molecular weight HA inhibited. The ability of HT1080 RHAMM-deficient cells, but not of CD44-deficient ones, to adhere was significantly decreased (p ≤ 0.001) as compared with control cells. Importantly, the effect of LMWHA on HT1080 cell adhesion was completely attenuated in RHAMM-deficient cells. In contrast, adhesion of RHAMM-deficient cells was not sensitive to high molecular weight HA treatment, which identifies RHAMM as a specific conduit of the LMWHA effect. Western blot and real time-PCR analyses indicated that LMWHA significantly increased RHAMM transcript (p ≤ 0.05) and protein isoform levels (53%, 95 kDa; 37%, 73 kDa) in fibrosarcoma cells. Moreover, Western blot analyses showed that LMWHA in a RHAMM-dependent manner enhanced basal and adhesion-dependent ERK1/2 and focal adhesion kinase (FAK) phosphorylation in HT1080 cells. Utilization of a specific ERK1/2 inhibitor completely inhibited (p ≤ 0.001) LMWHA-dependent adhesion, suggesting that ERK1/2 is a downstream effector of LMWHA/RHAMM signaling. Likewise, the utilization of the specific ERK1 inhibitor resulted in a strong down-regulation of FAK activation in HT1080 cells, which identifies ERK1/2 as a FAK upstream activator. In conclusion, our results suggest that RHAMM/HA interaction regulates fibrosarcoma cell adhesion via the activation of FAK and ERK1/2 signaling pathways.
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Affiliation(s)
- Katerina Kouvidi
- Department of Histology-Embryology, University of Crete, Heraklion 71003, Greece
| | - Aikaterini Berdiaki
- Department of Histology-Embryology, University of Crete, Heraklion 71003, Greece
| | - Dragana Nikitovic
- Department of Histology-Embryology, University of Crete, Heraklion 71003, Greece
| | - Pavlos Katonis
- Department of Orthopaedics, Medical School, University of Crete, Heraklion 71003, Greece
| | - Nikos Afratis
- Laboratory of Biochemistry, Department of Chemistry, University of Patras, Patras 26110, Greece
| | - Vincent C Hascall
- Cleveland Clinic, Biomedical Engineering ND-20, Cleveland, Ohio 44195
| | - Nikos K Karamanos
- Laboratory of Biochemistry, Department of Chemistry, University of Patras, Patras 26110, Greece
| | - George N Tzanakakis
- Department of Histology-Embryology, University of Crete, Heraklion 71003, Greece.
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Advanced analysis of nutraceuticals. J Pharm Biomed Anal 2011; 55:758-74. [DOI: 10.1016/j.jpba.2010.11.033] [Citation(s) in RCA: 196] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2010] [Revised: 11/19/2010] [Accepted: 11/23/2010] [Indexed: 01/18/2023]
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Gatti R, Andreatta P, Gioia MG, Boschetti S. A SIMPLE AND VALIDATED LC METHOD FOR THE SIMULTANEOUS ANALYSIS OF GLUCOSAMINE AND CHONDROITIN SULFATE EQUIVALENT IN DIETARY PRODUCTS. J LIQ CHROMATOGR R T 2010. [DOI: 10.1080/10826076.2010.526829] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- Rita Gatti
- a University of Bologna , Department of Pharmaceutical Science , Bologna, Italy
| | - Paolo Andreatta
- b E-Pharma Trento S.P.A., Research and Development , Ravina (TN), Italy
| | - Maria G. Gioia
- c University of Bologna, Faculty of Pharmacy , Bologna, Italy
| | - Silvia Boschetti
- b E-Pharma Trento S.P.A., Research and Development , Ravina (TN), Italy
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Krevvata MI, Afratis N, Spiliopoulou A, Malavaki CJ, Kolonitsiou F, Anastassiou E, Karamanos NK. A modified protocol for isolation and purity evaluation of a staphylococcal acidic polysaccharide by chromatography and capillary electrophoresis. Biomed Chromatogr 2010; 25:531-4. [PMID: 20734357 DOI: 10.1002/bmc.1490] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2010] [Accepted: 06/24/2010] [Indexed: 11/10/2022]
Abstract
The extracellular slime of Staphylococcus epidermidis contains, amongst various macromolecules, an acidic polysaccharide (PS) of a molecular mass of 20 kDa with significant antigenic and biological properties. The isolation procedure used so far includes multiple fractionations in anion-exchange chromatographic columns before its final purification by gel filtration chromatography. This protocol is laborious, time-consuming and includes the risk of unnecessary loss of PS quantities. Because of the significance of this PS, a modified protocol resulting in an easier and quicker isolation procedure was developed. Furthermore, identification, purity, charge density and molecular integrity of the isolated polysaccharide were evaluated by a reverse-polarity capillary electrophoresis method.
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Affiliation(s)
- Maria I Krevvata
- Laboratory of Microbiology, School of Medicine, University of Patras, Patras, Greece
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37
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Recent advances of capillary electrophoresis in pharmaceutical analysis. Anal Bioanal Chem 2010; 398:29-52. [DOI: 10.1007/s00216-010-3741-5] [Citation(s) in RCA: 105] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2010] [Revised: 04/08/2010] [Accepted: 04/09/2010] [Indexed: 01/16/2023]
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TAT STEEVEKWAN, PELLETIER JEANPIERRE, MINEAU FRANÇOIS, DUVAL NICOLAS, MARTEL-PELLETIER JOHANNE. Variable Effects of 3 Different Chondroitin Sulfate Compounds on Human Osteoarthritic Cartilage/Chondrocytes: Relevance of Purity and Production Process. J Rheumatol 2010; 37:656-64. [DOI: 10.3899/jrheum.090696] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Objective.During osteoarthritis (OA), the altered metabolism of cartilage involves proinflammatory factors and matrix metalloprotease (MMP) activity. Studies showed that chondroitin sulfate (CS) may exert a positive effect on the cartilage. Because of differences in CS in terms of purity and the production/purification process, we compared the effects of 3 different types of CS on human OA cartilage.Methods.Three types of CS were tested: CS1 (porcine, purity 90.4%), CS2 (bovine, purity 96.2%), and CS3 (bovine, purity 99.9%). Treatment with CS at 200 and 1000 μg/ml was performed on human OA cartilage explants in the presence/absence of interleukin 1ß (IL-1ß), and the protein modulations of factors including prostaglandin E2 (PGE2), IL-6, and MMP-1 measured by ELISA. The CS effect on the expression of collagen type II was also investigated on OA chondrocytes using quantitative polymerase chain reaction.Results.In the presence of IL-1ß, CS2 at 1000 μg/ml significantly inhibited IL-6 and PGE2 production, and CS3 at 200 μg/ml markedly reduced the level of IL-6. CS1 was much less efficient at reducing the catabolic markers and in the absence of IL-1ß, it significantly increased IL-6 and MMP-1. IL-1ß significantly inhibited the gene expression level of collagen type II; only CS3 was able to limit this inhibition. CS1, in the presence or absence of IL-1ß, further markedly decreased collagen type II expression.Conclusion.Our data indicate that among the 3 tested CS, CS1 increased production of some catabolic pathways and inhibited the gene expression level of collagen type II. Our study provides new information in the context of prescribing CS for alleviating OA symptoms, as the purity and/or production/purification of the CS compound could orient the current OA disease process toward increased catabolic pathways.
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High-performance liquid chromatography and on-line mass spectrometry detection for the analysis of chondroitin sulfates/hyaluronan disaccharides derivatized with 2-aminoacridone. Anal Biochem 2009; 397:12-23. [PMID: 19769935 DOI: 10.1016/j.ab.2009.09.030] [Citation(s) in RCA: 54] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2009] [Revised: 09/11/2009] [Accepted: 09/16/2009] [Indexed: 11/23/2022]
Abstract
In this study, we developed an on-line reverse-phase high-performance liquid chromatography-electrospray ionization-mass spectrometry (RP-HPLC-ESI-MS) separation and structural characterization of hyaluronan (HA)/chondroitin sulfate (CS)/dermatan sulfate (DS) disaccharides released by enzymatic treatment and derivatized with 2-aminoacridone (AMAC), providing a high-resolution system also applicable by using a further fluorimetric detector (Fp) before ESI-MS spectral acquisition. Isomeric nonsulfated HA and CS/DS disaccharides, isomeric monosulfated and isomeric disulfated CS/DS disaccharides, and the trisulfated species were distinctly separated and unambiguously identified by their retention times and mass spectra in negative ionization mode. In general, no multiply charged ions were detected even for highly charged disaccharides, but the presence of desulfonated products for highly sulfated species due to the relative instability of sulfo groups was observed. RP-HPLC-ESI-MS of each AMAC disaccharide was found to be linear from 3 to 500 ng with very high coefficient of correlation values due to the high efficiency of separation and the sharp outline of the peaks. Various CS/DS samples were characterized for disaccharide composition, and minor oligomer species identified as GalNAcSO(4) at the nonreducing end of chains was observed as a common component of these macromolecules. Furthermore, purified endogenous normal human plasma CS disaccharides were also evaluated by means of RP-HPLC-(Fp)-ESI-MS.
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Mania VM, Kallivokas AG, Malavaki C, Asimakopoulou AP, Kanakis J, Theocharis AD, Klironomos G, Gatzounis G, Mouzaki A, Panagiotopoulos E, Karamanos NK. A comparative biochemical analysis of glycosaminoglycans and proteoglycans in human orthotopic and heterotopic bone. IUBMB Life 2009; 61:447-52. [DOI: 10.1002/iub.167] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Abstract
Chondroitin sulfate (CS) is an omnipresent glycosaminoglycan with significant biologic roles. Chondroitin sulfate has not one structure but its polysaccharide backbone is modified to a smaller or higher degree according to the cell, tissue, species localization, and/or physiopathological stimuli. The potential of chondroitin sulfate for the therapy of osteoarthritis has been under investigation in several clinical trials, which have shown that it is safe and well tolerated. However, there are many issues still unresolved, such as the structure-modifying effects of CS in osteoarthritis, symptom-modifying efficacy in certain groups of patients, structure-activity-pharmacokinetic relationships, knowledge of mechanism of action, and better quality control of the preparations. Furthermore, ongoing basic research on its biologic role will probably show other therapeutic applications.
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Affiliation(s)
- Fotini N Lamari
- Department of Pharmacy, Laboratory of Pharmacognosy & Chemistry of Natural Products, University of Patras, Patras, Greece.
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