OBJECTIVE: This study was aimed to assess the efficacy and safety of two oral Symptomatic Slow Acting Drugs for Osteoarthritis (SYSADOAs)-Glucosamine Sulfate, Chondroitin Sulfate, and their combination regimen in the management of knee osteoarthritis (KOA).
METHODS: This systematic review was conducted according to PRISMA 2020 guidelines. A detailed literature search was performed from 03/1994 to 31/12/2022 using various electronic databases including PubMed, Embase, Cochrane Library, and Google Scholar, using the search terms-Glucosamine sulfate (GS), Chondroitin sulfate (CS), Knee osteoarthritis, Joint pain, Joint disease, and Joint structure, for literature concerning glucosamine, chondroitin, and their combination in knee osteoarthritis treatment. Cochrane Collaboration\'s Risk assessment tool (version 5.4.1) was used for assessing the risk of bias and the quality of the literature. The data was extracted from the included studies and subjected to statistical analysis to determine the beneficial effect of Glucosamine Sulfate, Chondroitin Sulfate, and their combination.
RESULTS: Twenty-five randomized controlled trials (RCTs) were included in this systematic review. In short, exclusively 9 RCTs for GS, 13 RCTs for CS, and 3 RCTs for the combination of GS and CS. All these studies had their treatment groups compared with placebo. In the meta-analysis, CS showed a significant reduction in pain intensity, and improved physical function compared to the placebo; GS showed a significant reduction in tibiofemoral joint space narrowing. While the combination of GS and CS showed neither a reduction in pain intensity, nor any improvement in the physical function. However, the combination exhibited a non-significant reduction in joint space narrowing. In the safety evaluation, both CS and GS have shown good safety profile and were well tolerated.
CONCLUSIONS: This meta-analysis revealed that the CS (with decreased pain intensity and improvement in the physical function), and GS (with significant reduction in the joint space narrowing) have significant therapeutic benefits. However, their combination did not significantly improve the symptoms or modify the disease. This may be due to the limited trials that are available on the combination of the sulfate forms of the intervention. Hence, there is a scope for conducting multicentric randomised controlled trials to evaluate and conclude the therapeutic role of CS and GS combination in the management of KOA.

Chondroitin sulfate (CS) is a natural macromolecule polysaccharide that is extensively distributed in a wide variety of organisms. CS is of great interest to researchers due to its many in vitro and in vivo functions. CS production derives from a diverse number of sources, including but not limited to extraction from various animals or fish, bio-synthesis, and fermentation, and its purity and homogeneity can vary greatly. The structural diversity of CS with respect to sulfation and saccharide content endows this molecule with distinct complexity, allowing for functional modification. These multiple functions contribute to the application of CS in medicines, biomaterials, and functional foods. In this article, we discuss the preparation of CS from different sources, the structure of various forms of CS, and its binding to other relevant molecules. Moreover, for the creation of this article, the functions and applications of CS were reviewed, with an emphasis on drug discovery, hydrogel formation, delivery systems, and food supplements. We conclude that analyzing some perspectives on structural modifications and preparation methods could potentially influence future applications of CS in medical and biomaterial research.

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.

OBJECTIVE: To review the data about the efficacy of esophagus protective agent based on the fixed combination of hyaluronic acid and chondroitin sulfate dissolved in the bioadhesive carrier (poloxamer 407) in the complex therapy of patients with erosive gastroesophageal reflux disease (GERD).
METHODS: A search in MEDLINE/PubMed, EMBASE, Cochrane, and Russian Science Citation Index of Scientific Electronic Library electronic databases was performed. Relevant original controlled studies of a fixed combination of hyaluronic acid and chondroitin sulfate as an esophagus protective agent in a population of patients with erosive GERD were included.
RESULTS: The final analysis included three studies that enrolled 181 patients with erosive GERD. All the studies had a uniform design with the assessment of the primary endpoints (complete epithelialization of esophageal erosions and complete resolution of heartburn) 28 days after the start of therapy. Meta-analysis of the three controlled trials has demonstrated that combination therapy with proton pump inhibitors (PPIs) and esophagus protective agents is significantly more effective than PPI monotherapy for complete epithelialization of esophageal erosions at 28 days of treatment (relative risk 1.267, 95% confidence interval 1.082-1.483, p=0.003; I2=21.19%), but did not differ for complete resolution of heartburn on the day 28 of treatment (relative risk 1.638, 95% confidence interval 0.660-4.067, p=0.287; I2=92.59%).
CONCLUSIONS: Combined therapy with PPI and Alfasoxx is significantly more effective than PPI monotherapy for the epithelialization of esophageal erosions in patients with erosive GERD.
Цель. Обобщить данные об эффективности применения эзофагопротектора, состоящего из фиксированного комплекса гиалуроновой кислоты и хондроитин сульфата, растворенных в биоадгезивном носителе (полоксамер 407), в комплексной терапии пациентов с эрозивной формой гастроэзофагеальной рефлюксной болезни (ГЭРБ). Материалы и методы. Поиск исследований проводился в электронных базах данных MEDLINE/PubMed, EMBASE, Cochrane и Российский индекс научного цитирования на базе Научной электронной библиотеки. Включались релевантные оригинальные исследования контролируемого дизайна с применением фиксированного комплекса гиалуроновой кислоты и хондроитин сульфата в качестве эзофагопротектора на популяции пациентов с эрозивной формой ГЭРБ. Результаты. В итоговый анализ включено 3 исследования с участием 181 пациента с эрозивной формой ГЭРБ. Все работы выполнены по единообразному дизайну с оценкой основных конечных точек (полная эпителизация эрозий пищевода и полное разрешение изжоги) через 28 дней от начала терапии. Метаанализ 3 контролируемых исследований продемонстрировал, что комбинированная терапия с применением ингибиторов протонной помпы (ИПП) и эзофагопротектора достоверно эффективнее монотерапии ИПП для полной эпителизации эрозий пищевода на 28-е сутки лечения (относительный риск 1,267, 95% доверительный интервал 1,082–1,483, p=0,003; I2=21,19%), однако не различается относительно полного купирования изжоги на 28-е сутки лечения (относительный риск 1,638, 95% доверительный интервал 0,660–4,067, p=0,287; I2=92,59%). Заключение. Комбинированная терапия с применением ИПП и Альфазокса достоверно эффективнее монотерапии ИПП для эпителизации эрозий пищевода у пациентов с эрозивной формой ГЭРБ.

Currently, colorectal cancer is the third most common cancer in the world. Recently, glucosamine and chondroitin have gained popularity for their beneficial effects on cancer. They have already been recognized for their therapeutic role in osteoarthritis. This systematic review aims to analyze the relationship between the combined consumption of glucosamine and chondroitin and the prevention of colorectal cancer. Three databases: PubMed, Google Scholar, and Science Direct, were searched to collect relevant articles. After screening full-text articles, seven studies were included in the systematic review. The review found a supportive association between glucosamine and chondroitin and the decreased incidence of colorectal cancer. Through an anti-inflammatory effect on the cell signaling pathway, the supplementation caused a reduction in colorectal cancer occurrence. The dose, frequency of usage of the supplement, and weight of individuals, along with the use of non-steroidal anti-inflammatory drugs, also affected the efficacy. To further assess this relationship, it is necessary to conduct double-blind, randomized controls trials for the supplements in cancer prevention and further explore their safety and efficacy with different ethnicities, drugs, doses, and weight individuals.

Animal origin chondroitin sulfate is employed as anti-inflammatory drug and food supplement against anti-osteoarthritis, but also as antioxidant, antitumor, anticoagulant, and immune-regulatory agent or as biomaterial in tissue engineering scaffolds and in drug-delivery systems. As its biological properties depend on the structural characteristics, multi-analytical approaches are necessary to correlate specific features of its heterogenic composition to the different bioactivities. This is of paramount importance to assess the efficacy of pharmaceuticals and food supplements, beyond safety quality control. This review would address the issue of chondroitin sulfate characterization according to the Pharmacopeia testing monograph point of view giving an update of the analytical novelties reported in the last ten years that might be employed for the product testing and releasing on the market. Not-instrumental (e.g. colorimetric assays) and instrumental techniques, most of them coupling diverse chromatographic separation methods with spectroscopic and spectrometry detection techniques, mono and bi-dimensional NMR approaches, are compared as tools to evaluate identity, titer, purity grade, monosaccharide and disaccharide composition, averaged molecular weight and viscosity, charge and sulfate content, impurities and related substances including the presence of other glycosaminoglycans.

Ophthalmic viscoelastic devices (OVDs) are currently used in cataract surgery and have significantly improved the safety and effectiveness of this surgical procedure. OVDs are classified according to the zero-shear viscosity and the cohesion-dispersion index in cohesive, dispersive, and viscoadaptives. OVDs create and maintain anterior chamber depth and visibility, protecting the corneal endothelium and other intraocular tissues during surgery. The selection of the most adequate OVD is especially relevant when performing cataract surgery in challenging cases, such as in hard, mature cataracts, flat anterior chamber, pseudoexfoliation syndrome, intraoperative floppy iris syndrome, or glaucoma surgery. In such cases, OVD is crucial for facilitating the surgical procedure and the associated minimal complication rate. The use of a combination of OVDs (soft-shell technique and modifications), the use of blue-colored OVDs, and the combination of sodium hyaluronate with lidocaine have also been described as useful tools in some of these challenging cases.

Glucosamine and chondroitin sulfate have been proposed due to their physiological and functional benefits in the management of osteoarthritis in companion animals. However, the scientific evidence for their use is still controversial. The purpose of this review was to critically elucidate the efficacy of these nutraceutical therapies in delaying the progression of osteoarthritis, evaluating their impact on the synovial knee joint tissues and biochemical markers in preclinical studies by systematically reviewing the last two decades of peer-reviewed publications on experimental osteoarthritis. Three databases (PubMed, Scopus and, Web of Science) were screened for eligible studies. Twenty-two articles were included in the review. Preclinical studies showed a great heterogeneity among the experimental designs and their outcomes. Generally, the evaluated nutraceuticals, alone or in combination, did not seem to prevent the subchondral bone changes, the synovial inflammation or the osteophyte formation. However, further experimental studies may be needed to evaluate their effect at those levels. Regarding the cartilage status and biomarkers, positive responses were identified in approximately half of the evaluated articles. Furthermore, beneficial effects were associated with the pre-emptive administrations, higher doses and, multimodality approaches with some combined therapies. However, additional studies in the long term and with good quality and systematic design are required.

Glycosaminoglycans are native components of the extracellular matrix that drive cell behavior and control the microenvironment surrounding cells, making them promising therapeutic targets for a myriad of diseases. Recent studies have shown that recapitulation of cell interactions with the extracellular matrix are key in tissue engineering, where the aim is to mimic and regenerate endogenous tissues. Because of this, incorporation of glycosaminoglycans to drive stem cell fate and promote cell proliferation in engineered tissues has gained increasing attention. This review summarizes the role glycosaminoglycans can play in tissue engineering and the recent advances in their use in these constructs. We also evaluate the general trend of research in this niche and provide insight into its future directions.

Osteoarthritis (OA) is the most prevalent musculoskeletal disease and a major cause of negative relevant outcomes, associated with an ever-increasing societal burden. Pharmaceutical-grade chondroitin sulfate (CS) was repeatedly reported to reduce pain and improve function in patients with OA. This article aims to review the evidence for the role of highly purified (hp) CS (Condrosulf®, IBSA) in the treatment of OA. We collected and reported evidence concerning (1) efficacy of hpCS 800 mg/day in the treatment of OA affecting the knee, hand and hip; (2) efficacy and safety of hpCS 1200 mg/day also in the oral gel formulation; (3) the safety profile of hpCS; (4) the difference of hpCS and pharmaceutical-grade formulations versus food supplements; (5) pharmacoeconomic added value of hpCS. The data support that hpCS is an effective and safe treatment of OA, with its effect already evident at 30 days; in addition, its beneficial action is prolonged, being maintained for at least 3 months after the drug is discontinued. Full safety reports\' analyses confirm that CS is safe to use and has almost no side effects, in particular, it showed better gastrointestinal tolerance if compared with non-steroidal anti-inflammatory drugs (NSAIDs). Moreover, the therapeutic strategy has proved to be cost-effective: treatment with CS reduced the use of NSAIDs and their side effects.