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Osteoarthritis (OA) is one of the leading causes of disability in the world, but the efficacy and safety of its treatment remain extremely low. This review presents epidemiology of OA, mechanism of its development and modern possibilities of pharmacological regulation of immune-mediated inflammation in OA. We analyze the immunological aspects of oral tolerance phenomenon and the prospects for its use to suppress autoinflammation in OA using combined pharmaconutraceutical preparation Chondroguard® TRIO as an element of nutritional support for patients with this disease. It is emphasized that it is advisable to develop a scientifically based rational approach to the treatment of OA that alleviates symptoms, reduces autoinflammatory affection of articular cartilage and improves its regeneration with the involvement of extracellular matrix components.

In this study, HCl and H2SO4 were used to compare the best conditions for producing glucosamine from the dry chitin of shrimp shells. The results showed that for HCl hydrolysis, the most favored conditions were 12 M, 80 °C, 2 hours, and a chitin-to-acid volume ratio of 1:20, whereas, for H2SO4 hydrolysis, the most favored conditions were 6 M, 90 °C, 5 hours, and a chitin to acid volume ratio of 1:20. HCl produced pured glucosamine with a higher yield than H2SO4. Additionally, our findings indicated that glucosamine could be detected using a UV detector with a weak signal, whereas we recommended using an RI detector for a comparably stronger signal. Our production maximum yield of 283.9 ± 13.8 mg Gln g−1 chitin from HCl hydrolysis was comparable to that of other studies, with a comparison between using HCl and H2SO4 being highlighted.

Aim: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate the effects of the combined hydrolyzed type 2 collagen, methylsulfonylmethane (MSM), glucosamine sulfate (GS), and chondroitin sulfate (CS) supplement on knee pain intensity in patients with knee osteoarthritis (OA). Patients and methods: This multicenter, observational, noninterventional study included 98 patients (78 females, 20 males; mean age: 52.8±6.5 years; range, 40 to 64 years) who had Grade 1-3 knee OA between May 2022 and November 2022. The patients were prescribed the combination of hydrolyzed type 2 collagen, MSM, GS, and CS as a supplement for knee OA. The sachet form of the combined supplement containing 1250 mg hydrolyzed type 2 collagen, 750 mg MSM, 750 mg GS, and 400 mg CS was used once daily for two consecutive months. Patients were evaluated according to the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Visual Analog Scale (VAS)-pain, and Health Assessment Questionnaire (HAQ). Patients were scheduled to visit for follow-up four weeks (Visit 2) and eight weeks (Visit 3) after Visit 1 (baseline; day 0 of the study). Results: For the VAS-pain, WOMAC, WOMAC-subscale, and HAQ scores, the differences in improvement between the three visits were significant (p<0.001 for all). The patient compliance with the supplement was a median of 96.77%, both for Visit 2 and Visit 3. Conclusion: The combination of hydrolyzed type 2 collagen, MSM, GS, and CS for eight weeks in knee OA was considered an effective and safe nutritional supplement. [ABSTRACT FROM AUTHOR]

The data on the classification of drugs, which are prescribed for the treatment of patients with joint and spine diseases, such as osteoarthritis (OA) and rheumatoid arthritis (RA), are presented. The groups of drugs widely used in clinical practice are disease-modifying osteoarthritis drugs (DMOADs) and disease-modifying antirheumatic drugs (DMARDs). To help the practitioner, consolidated information is provided on the main differences between these groups according to the mechanism of action (immunomodulatory vs. immunosuppressive) and the main indications for use (autoinflammatory joint diseases (OA) vs. autoimmune joint diseases (RA, psoriatic arthritis, ankylosing spondyloarthritis)). The material of the article is focused on the clinicians to help them make a right choice of OA therapy, and to identify the problem of drug choice in RA. Information about the possibility of using nutritional support in patients with OA is presented.

A meeting of the Expert Council on September 9, 2023 considered the last challenges in the treatment of osteoarthritis (OA) including OA in comorbid patients. Leading experts in rheumatology, traumatology and other relevant disciplines participated in the meeting. The key goal of Expert Council was the discussion of potential application of a combination of undenatured (native) type II collagen, methylsulfonylmethane, boswellic acids, vitamins C and D (Artneo complex) as a part of complex OA therapy. The experts concluded that Artneo for stage I–III knee OA patients is not just non-inferior in comparison with a combination of chondroitin sulfate and glucosamine hydrochloride but excels it in the decrease of magnetic resonance imaging synovitis markers and dynamics of Lequesne index for knee osteoarthritis severity. The proven efficacy and the favorable safety profile of 6-months Artneo course deserve the attention of medical community and the active implementation of Artneo complex into ambulatory practice, first of all, for the treatment of patients with mild or moderate synovitis and/or burdened with comorbidities.

Introduction: Rheumatoid arthritis (RA) is a common health problem with a serious impact on quality of life. Hence, variable therapeutic regimens have been tested to ameliorate the symptoms and hinder the disease progression. Aim of the Work: To assess the therapeutic effect of ginger (GR) or glucosamine sulfate (GAS) separately versus their combined administration in a rat model of induced-RA. Materials and Methods: Sixty adult female albino rats were allocated into five groups; 20 rats were the control group I. RA was induced by a single intra-articular injection of 100 μL of Complete Freund’s Adjuvant (CFA) in the knee joints of the remaining forty rats, then distributed after 7 days into: RA group II, GR group III (received 400 mg GR/kg/day), GAS group IV (received 250 mg GAS/kg/day), and combined treatment group V. Treatment groups were euthanized after 28 days. Assessment of serum levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) was done. Right knee joints were dissected for gross macroscopic and scanning electron microscope (SEM) examinations. Left knee joints were processed for a histological examination by hematoxylin and eosin (H & E) and Masson’s trichrome stains. Results: In group V, serum levels of TNF-α and IL-6 restored nearly their control values. Gross and SEM examinations revealed mostly regular articular cartilage surfaces. Histologically, mostly smooth cartilage surfaces were observed with preserved joint space and distinct cartilage zones, in comparison to GR and GAS treated groups that exhibited limited surface irregularities and invasion of the joint space by pannus tissue, in some sections. Trichrome stained sections demonstrated a significant decline in percentage area of collagen within the pannus in group V as compared to RA group. Conclusion: The combined treatment enhanced the therapeutic effect of GR and GAS, thus resulted in the most prominent improvement in all assessed parameters. [ABSTRACT FROM AUTHOR]

The review examines pharmacological agents that can have potential disease-modifying osteoarthritis drugs (DMOADs) status. DMOADs prevent the progression and further structural joint damage (structure-modifying effect), leading to a decrease in symptoms severity (symptom-modifying effect), such as pain, and improvement of joint function. Approaches to potential DMOADs selection are discussed: (1) the preferred target (bone, cartilage, synovia); (2) action drug mechanism/anti-cytokine therapy (matrix metalloproteinase inhibitors, inhibitors of pro-inflammatory interleukins, etc.). The main delivery systems of drugs claiming to be of DMOADs status and possible contribution of immunological mechanisms to osteoarthritis pathogenesis are considered. Methods evaluating the effectiveness of DMOADs therapy are of great interest (cytology, microscopy, radiological research methods, blood and synovia biochemical markers). Based on research results analysis, the following substances can be considered as potential DMOADs: chondroitin sulfate, glucosamine sulfate, undenatured type II collagen, vitamin D. Each of them has symptom-modifying and structural-modifying effects.

Understanding the major pathological pathways and the key molecules involved in the pathogenesis of inflammatory processes in joints, particularly in osteoarthritis (OA), is crucial for drug and pharmaconutraceuticals development. OA is a degenerative joint disease that predominantly affects articular cartilage. Destruction of hyaline cartilage and restructuring of subchondral bone are accompanied by synovial inflammation in the joint, including the facet joint of the spine, manifested by pain in the joint, low back pain (LBP), and limitation of functional activity. The article discusses the relationship between immune and inflammatory mechanisms in OA of any location, including the joints of the spine. One of the mechanisms for the formation of a “vicious circle of inflammation” during the activation of discoidin receptors by endogenous type II collagen is discussed, leading to the induction of the synthesis of pro-inflammatory mediators: tumor necrosis factor α(TNFα), metalloproteinases (MMPs) 1 and 13, interleukins (IL) 1 and 6. Inflammation, in turn, leads to a decrease in the synthesis and destruction of endogenous type II collagen and, subsequently, to cartilage destruction. Cartilage fragments entering the joint space of the intercellular matrix enhance the synthesis of TNFα, IL, and MMP and exacerbate the inflammatory process. Oral ingestion of exogenous undenatured type II collagen(NK-II) helps, first, to inactivate the binding of fragments of destroyed endogenous type II collagen to discoidin receptors and to break the "vicious circle of inflammation"; secondly, through the mechanism of oral/intestinal tolerance via the lymphoid system in Peyer's patches of the small intestine, leads to the activation of immune cells (T-lymphocytes) and initiation of the immune response – the synthesis of anti-inflammatory mediators (transforming growth factor β, IL4 and IL10). The new pharmaconutraceutical Chondroguard®TRIO, which contains chondroprotectors (chondroitin sulfate and glucosamine sulfate) as well as NK-II, will make it possible to influence the key sites of the pathological process in OA.

The review considers the full spectrum of currently known autoantigens in osteoarthritis (OA) and discusses their role in the development and/or persistence of synovitis and the initiation of subsequent destruction of articular cartilage with the development of an autoimmune response and auto-inflammation. Of great interest are methods of drug prevention of OA considering autoimmunity responses and associated auto-inflammation, including the use of pharmaconutraceuticals.Preclinical and clinical studies of the safety and efficacy of pharmaconutraceuticals containing native type II collagen are presented. A clear relationship between the composition/chemical structure of the collagen components and its mechanism of action and efficacy is discussed. Taking into account the autoimmune pathogenesis of OA, new combined pharmaconutraceuticals aimed at reducing the manifestations of autoinflammation (chondroitin sulfate, glucosamine sulfate) are developed. They have an optimal ratio of active ingredients with a sufficient level of evidence, which allows enhancing their beneficial pharmacological effects.

Osteoarthritis (OA) is a painful and disabling disease that affects millions of people around the world. OA is the most common form of arthritis and is characterized by joint pain and stiffness, leading to a decrease in functional activity and loss of quality of life. Approaches to OA therapy are constantly being revised, as new molecules appear, data on drugs/molecules already in use, including data on adverse events, new randomized controlled trials results, new methods of adjunctive therapy become available. OA therapy and prevention, drugs with chondroprotective properties are prescribed according to the opinion of European experts (2019): chondroitin sulfate (CS), glucosamine sulfate (GS), diacerein, avocado soybean unsaponifiables, hyaluronic acid (HA) for intra-articular administering. Only CS and GS have proven effectiveness and the level of recommendations A1, they are included in clinical recommendations and standards of the Ministry of Health of the Russian Federation (MHRF), and international recommendations according to which CS and GS should be used for a long time (up to 6 months). The article focuses on the analysis of erroneous statements regarding the classification, composition and mechanisms of action of different drugs of this group. Differences in terminology of drug groups are given, such as: chondroprotectors, symptomatic slow acting drugs for osteoarthritis (SYSADOAs), disease-modifying osteoarthritis drugs, between which an equal sign cannot be placed. Based on the analysis, a conclusion was made about erroneous attitudes towards some SYSADOAs: 1) according to the Anatomical Therapeutic Chemical Classification, the active substances CS, GS, diacerein and HA are classified as nonsteroidal anti-inflammatory drugs due to their antiinflammatory activity; 2) quite often, drugs based on bioactive concentrate of small sea fish and glycoaminoglycan-peptide complex do not belong to SYSADOAs according to any of the existing generally recognized classifications, they do not contain a sufficient amount of active substances (CS or peptides), there is no proper level of evidence, they are not included in the recommendations of international medical communities and MHRF clinical recommendations and standards. In Russia, physicians must follow MHRF clinical guidelines and standards for OA therapy.

This study investigated the role of a pattern of microRNA (miRNA) as possible mediators of celecoxib and prescription-grade glucosamine sulfate (GS) effects in human osteoarthritis (OA) chondrocytes. Chondrocytes were treated with celecoxib (1.85 µM) and GS (9 µM), alone or in combination, for 24 h, with or without interleukin (IL)-1β (10 ng/mL). Cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, apoptosis and reactive oxygen species (ROS) by cytometry, nitric oxide (NO) by Griess method. Gene levels of miRNA, antioxidant enzymes, nuclear factor erythroid (NRF)2, and B-cell lymphoma (BCL)2 expressions were analyzed by quantitative real time polymerase chain reaction (real time PCR). Protein expression of NRF2 and BCL2 was also detected at immunofluorescence and western blot. Celecoxib and GS, alone or in combination, significantly increased viability, reduced apoptosis, ROS and NO production and the gene expression of miR-34a, -146a, -181a, -210, in comparison to baseline and to IL-1β. The transfection with miRNA specific inhibitors significantly counteracted the IL-1β activity and potentiated the properties of celecoxib and GS on viability, apoptosis and oxidant system, through nuclear factor (NF)-κB regulation. The observed effects were enhanced when the drugs were tested in combination. Our data confirmed the synergistic anti-inflammatory and chondroprotective properties of celecoxib and GS, suggesting microRNA as possible mediators. [ABSTRACT FROM AUTHOR]

In recent decades, there has been an increase in the prevalence and medical and social burden of osteoarthritis (OA) and nonspecific back pain in all countries of the world. The First Multidisciplinary Bilateral Russia-Uzbekistan Expert Council presented innovations in the prognosing, personalized prevention and adjuvant therapy of degenerative-dystrophic diseases of the joints and spine, the evidence base for the effectiveness and safety of the use of drugs that modify the course of OA (Disease-modifying osteoarthritis drugs, DMOADs): chondroitin sulfate, glucosamine sulfate, undenatured type II collagen for adjuvant pharmaconutraceutical support – prevention and adjuvant therapy (treatment) of OA and nonspecific lumbosacral pain. The expert counsil resolution presents an optimized algorithm for the management, prevention and adjuvant therapy of OA and non-specific back pain, maintaining the function of healthy joints after intense physical activity with the inclusion of the drug Chondroguard solution for intra-articular and intramuscular administration (INN – chondroitin sulfate) and a new pharmaconutraceutical from the DMOADs group – TRIO trademark Chondroguard® (Chondroguard®TRIO).

Backpain and pain in the limbs are often associate with the destruction of the cartilage and bone tissue of the joint, which affects the nerve terminals and leads to an exacerbation of pain symptoms (as happens, for example, in osteoarthritis). As a result, pain relief without protection and reconstruction of cartilage (chondroprotection), will be symptomatic. The chondroprotective effects of glucosamine sulfate (GS), chondroitin sulfate (CS) and undenatured type II collagen (UC-II) have different molecular mechanisms. Therefore, with the combined use of CS, GS and UC-II per os, different mechanisms of action of individual components will complement each other, increasing the effectiveness of pain pharmacotherapy.

Abstract Background Several studies have reported that glucosamine sulfate (GS) can improve knee osteoarthritis (OA) symptomatology. In parallel, the disease-modifying effects of non-steroidal anti-inflammatory drugs (NSAIDs) in knee OA have also been investigated. However, limited literature has reported the combined effect of GS and NSAIDs. The aim of this scoping review is to describe the scope and volume of the literature investigating the potential benefits and synergistic effect of a combination of GS and NSAIDs in patients with knee OA. Methods PubMed and Embase were searched for studies published from inception through April 2022, evaluating the effects of the combination of GS and NSAIDs in OA patients, versus either treatment alone. Data are reported narratively. Results Five studies were included in this review; 4 were randomized control trials and one was a prospective observational study. The duration of combination treatment was 6 to 12 weeks. The combination was compared to celecoxib in 2 studies, meloxicam in 1, etoricoxib in 1, and a conventional NSAID in 1 (ibuprofen or piroxicam). All 5 studies reported that in patients with knee OA, the combination of GS plus NSAID yielded a significantly greater benefit than single-agent therapy, in terms of outcomes including pain reduction, function, joint stiffness, and markers of inflammatory activity and cartilage degradation. Conclusion The 5 studies included in this scoping review all report a significantly greater clinical benefit with a combination of GS plus NSAID compared to either treatment alone. The evidence supports efficacy in reducing pain, improving function, and possibly regulating joint damage. However, further randomized trials with larger sample sizes are warranted to confirm these findings.

The relationship between the pathophysiology of osteoarthritis (OA) and metabolic disorders (metabolic syndrome, obesity) is provided not only by mechanical causes (increased body weight pressure on the joints). A complex of molecular mechanisms, which mediates OA effect on the development of obesity, was established. Excessive activity of toll receptors, the NF-κB cascade, and metabolic disorders of endogenous chondroitin sulfates (CS) lead to chronic inflammation and the development of a complex of comorbid pathologies, including OA, atherosclerosis, and obesity. The relationship between insulin resistance and CS metabolism is also mediated by impaired genomic DNA methylation. Exogenous CS and glucosamine sulfate (GS) used in the long-term treatment of OA also contribute to the inhibition of the pathophysiology of obesity. By inhibiting O-glucosamination of intranuclear proteins (i.e., p53), GS can accelerate lipolysis of visceral fat. Anti-inflammatory effects of CS and GS is associated with inhibition of toll receptors and NF-κB, increased levels of antioxidant enzymes, regulation of expression of fibroblast growth factor 21, activation of adenosine monophosphate-activated protein kinase, and inhibition of secretion of chemoattractant protein MCP-1 and pancreatic lipase. Positive effect of CS and its oligosaccharides exposure on the pathophysiology of metabolic disorders is associated not only with a decrease in inflammation and normalization of fat metabolism but also with an improvement in the state of the intestinal microbiota. Experimental and clinical studies confirm the effects of CS and GS on body mass control. CS and GS are effective and safe when used in patients with OA associated with metabolic syndrome and/or obesity.

Background. Osteoarthritis of the knee (OAK) causes severe pain and sometimes disability, which reduces the quality of life and work capacity of patients. Today, the prevalence of OAK is increases; therefore, the development of methods for its treatment and the use of means that slow down or stop the progression of OAK are relevant. Since OAK is a slowly progressive disease, the search for effective drugs with minimal toxicity and a long-lasting effect, which prevent the destruction of articular cartilage and improve the working conditions of the patient, is ongoing. Thus, the main goals of OAK treatment are to reduce symptoms and slow the progression of the disease, which can reduce the negative impact of OAK on the patient’s functional capacity, as well as improve quality of life. OAK is characterized by the progressive destruction of the articular cartilage, especially when it bears a load. In the joint, cartilage aggrecan is the main structural component that provides hydrophilicity and allows to withstand compression loads. Aggrecan is a complex of proteoglycans with hyaluronic acid and is characterized by a high content of chondroitin sulfate chains, while proteoglycan consists of protein and glycosaminoglycan chains (the precursor of the latter is glucosamine). Therefore, it is believed that the treatment of OAK with glucosamine sulfate and chondroitin sulfate can stimulate the synthesis of proteoglycan and thereby slow down the process of joint degeneration and promote their recovery in OAK. These cartilage metabolites are produced in the human body and are important components of joints for their functioning. Purpose: to conduct an analysis of literature data on the effectiveness of chondroprotective agents in comparison with other pharmacological groups for the elimination of pain and inflammation during the treatment of OAK. Materials and methods. The search for scientific information was carried out in PubMed, Google Scholar electronic databases. Results. A search for literature on chondroprotective agents was conducted and the effectiveness of chondroprotective agents to eliminate pain and inflammation in the treatment of OAK was analyzed in comparison with other pharmacological groups. Conclusions. Chondroprotective agents have particular advantages in the symptomatic treatment of OAK: chondroitin sulfate is a natural glycosaminoglycan (found in cartilage and extracellular matrix) and therefore has advantages in the symptomatic treatment of OAK due to its anti-inflammatory activity. Besides, in OAK, chondroitin sulfate provides resistance to compression, maintaining the structural integrity of cartilage, and homeostasis, slowing down its destruction and reducing pain in inflamed muscles. It is most often used in combination with glu cosamine sulfate for the treatment of OAK, as the latter plays a key role in the regulation of the processes of cell development and ad hesion, proliferation and differentiation of cartilage. These agents (glucosamine sulfate, chondroitin sulfate) are used as symptomatically slow-acting drugs in OAK. No serious side effects or overdos es have been reported in the literature, suggesting their safety in the long-term treatment of OAK. [ABSTRACT FROM AUTHOR]

Carbohydrate compounds are recognized potent green corrosion inhibitors owing to their structural properties and eco-friendliness. This study showed the effectiveness of glucosamine sulfate (GAS), an eco-friendly green inhibitor, in mitigating the deterioration of 6061 aluminium alloy reinforced with 2% SiC and 2% B _4 C hybrid composite (6061AA-HMMC) material in 0.1 M hydrochloric acid (HCl) medium. Electrochemical measurements were carried out to quantify the corrosion rate in the absence and presence of the GAS. The results were included in an acceptable adsorption isotherm model, and a suitable mechanism for the corrosion inhibition process was discussed in detail. To comprehend the method of adsorption, the Freundlich isotherm model was applied. Different characterization techniques were used to verify the adsorption of the investigated inhibitor. The optimized structure of the GAS was analysed using density functional theory to provide further insight into its interaction with the metal surface. The infrared (IR) and UV-visible (UV) spectra for the adsorption of the inhibitor molecule were compared with the IR and UV spectra calculated by B3LYP/6-311++G(d, p).

Standardized extracts of undenatured type II collagen (UC-II) are used as alternative approaches to the treatment of osteoarthritis (OA). The effect of UC-II extracts is associated with the modulation of the mechanisms of innate and acquired immunity, a decrease in the activity of proinflammatory cytokines and prostaglandins. Epitopes of native collagen in the structure of UC-II contribute to a decrease in the activity of autoimmune reactions that stimulate cartilage degradation. Interacting with discoidin receptors, UC-II accelerates the reconstruction of cartilage connective tissue and inhibits the pro-inflammatory effects of endogenous collagens. Experimental and clinical studies confirm the effectiveness of the use of standardized substances UC-II for acceleration of cartilage regeneration and reduce pain in OA and subclinical joint dysfunction.

The article presents new views on the treatment of pain syndromes in musculoskeletal diseases, in particular in osteoarthritis (OA) of various localizations (gonarthrosis, coxarthrosis). New recommendations (2019–2020) of international societies for the study of symptomatic delayedacting drugs (SYSADOA) and their use in the treatment of OA are presented. We present the opinions of experts from different communities: the American College of Rheumatology (ACR, 2019), the European Alliance of Associations for Rheumatology (EULAR, 2019), the European Society for the Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO, 2020) – on the prescription of SYSADOA, which include chondroitin sulfate (CS), glucosamine sulfate (GS), avocado and soy unsaponifiable compounds, diacerein, hyaluronic acid for intraarticular administration. New domestic clinical guidelines (2020–2021) for the treatment of OA are presented. The changes that have taken place in the terminology of pain and in the classification of pain syndromes, reflected in the new International Classification of Diseases of the 11th revision (ICD-11), are analyzed. New approaches to the stratification of OA, taking into account endo- and phenotyping, as well as new aspects in pain therapy associated with the molecular genetic mechanisms of SYSADOA are shown. According to the EULAR recommendations, there is indisputable evidence of the efficacy and safety of pharmaceutical CS, which is reflected in a meta-analysis (2019), a randomized placebo-controlled trial (2019), approved by the Russian Ministry of Health, and confirmed in Chondroguard’s meta-analysis of clinical trials (2020). New approaches in the treatment of pain syndromes provide for parenteral administration of CS and GS according to an intermittent scheme. The search and development of new molecules comparable in efficacy to SYSADOA in the treatment of pain in OA and low back pain have led to the emergence in clinical practice of biologically active compositions, including undenatured type II collagen, the effectiveness of which is associated with a neuroimmune mechanism of action.

Osteoarthritis (OA) is a multifactorial disease that can be caused by genetic factors, obesity, joint microtrauma, and excessive physical exercises. The key features of OA include gradual loss of articular cartilage, bone tissue remodeling, development of osteophytes, and subchondral sclerosis. The pathogenesis of OA is based on the loss of glycosaminoglycans, collagen disorganization, and inflammation mediated by a cytokine cascade. OA is a complex disease affecting not only cartilage, but also intraarticular and periarticular tissues. Together, these changes compromise joint function and cause chronic pain. Considerable attention has beer recently paid to OA phenotyping in order to introduce a tailored approach into patient management. Phenotypes are applicable to the three most common peripheral OA locations: gonarthrosis, coxarthrosis, and hand OA. An international group of experts of primary care has developed algorithms for OA patient management, including diagnostic criteria, treatment options, and criteria for referring the patient to a specialist (rheumatologist). Current guidelines recommend non-drug therapy, pharmacotherapy, and surgery. There is a growing interest in phytopharmaceuticals, a heterogeneous group of molecules with a high capacity of suppressing inflammation, oxidative stress, and pain, as well as improving joint function. Mucosate® in capsules (DIAMED-pharma, Russia) is one of currently available complex products with phytocompounds. It contains the NEM® complex (natural eggshell membrane), Harpagophytum root extract, glucosamine sulfate, chondroitin sulfate, and manganese sulfate monohydrate.

Back pain is one of the most common causes of a doctor visit and occupy the first place among all non-infectious diseases in terms of the number of years of life, lost due to persistent deterioration in health. Nonspecific (musculoskeletal) pain represents the most common cause of pain and can be caused by the intervertebral disc extrusion, the lesion of the facet joints, the sacroiliac joints pain (SJP), the myofascial syndrome. A comprehensive (interdisciplinary) approach to the treatment of chronic back pain is aimed not only at reducing pain, but also at increasing physical, social and domestic activity, improving the emotional state, and developing effective stereotypes of behavior. The personalized approach is based on the patient clarifying both anatomical causes of pain and social and psychological, including erroneous ideas about the causes of back pain and its forecast, depression, increased anxiety and insomnia. Kinesitherapy represents the most effective direction when conducting patients with chronic back pain and should be combined with avoiding excessive static and physical exertion. In addition to therapeutic exercises, regular walks are of great importance, the intensity and volume of which can gradually increase. Psychological methods of therapy, mainly cognitive-behavioral therapy (CBT), are effective for chronic nonspecific back pain, they also use in the presence of emotional disorders and insomnia. In case of damage to the facet joints, the SJP, combined osteoarthritis of the knee and hip joints for chronic back pain as additional therapy, combined drugs of chondroitin sulfate and glucosamine sulfate are used. Unfortunately, in our country, a personalized approach is rarely used, including the CBT, but its use can help many patients with chronic back pain.

Eggshell membrane (ESM), a thin membrane lining the eggshell of chicken eggs, is a natural byproduct attracting the attention of many researchers worldwide due to its valuable composition and beneficial biological activities. Its main active ingredients include collagen (types I, V, X), glucosamine sulfate, chondroitin/dermatan sulfate, and hyaluronic acid, so it possesses a beneficial value for maintaining healthy joints. Variation in eggshell color/breed of hens has been reported to affect the quality and composition of eggs and eggshells. So, the current study aimed to compare glucosamine sulfate content in ESM separated from white and brown eggs using the HPLC technique and UV detection at 195 nm. The peak area quantification method was used to determine the concentration of glucosamine in both samples. Results revealed that ESM separated from white eggs has a higher content of glucosamine sulfate (11.83% w/w) than ESM separated from brown eggs (10.68% w/w). We conclude that the use of ESM from white eggs may be more valuable than ESM from brown eggs in further biological studies to determine the effect of ESM in the prevention and management of osteoarthritis.

The aim of this study was to develop a topically applied formulation with the potential to alleviate arthritis ailments. A combination of two active ingredients, icariin from Epimedium L. (Species: Epimedium Koreanum) extract as a potential promoter of chondrogenesis and glucosamine sulfate as a precursor of cartilage tissues, was tested. In permeation studies, the potential for skin permeation of both substances was confirmed; however, the in vitro release test did not accurately reflect the degree of skin permeation. The in vitro release of icariin was at a level of 15.0–19.0% for the plant-extract-derived icariin and 29.0–35.0% for the pure substance. The level of glucosamine sulfate release was 38.4% (on average). For icariin of both origins, the release results were higher than those obtained via oral administration (about 12.0%), which shows the potential superiority of topical application. In addition, the physicochemical parameters that affect the in vitro release and performance of topical formulations were addressed. This preliminary research and permeation analysis of the formulation produced a promising picture of its prospects regarding arthritis treatment, although further investigation is needed. [ABSTRACT FROM AUTHOR]

Background: Several studies have reported that glucosamine sulfate (GS) can improve knee osteoarthritis (OA) symptomatology. In parallel, the disease-modifying effects of non-steroidal anti-inflammatory drugs (NSAIDs) in knee OA have also been investigated. However, limited literature has reported the combined effect of GS and NSAIDs. The aim of this scoping review is to describe the scope and volume of the literature investigating the potential benefits and synergistic effect of a combination of GS and NSAIDs in patients with knee OA. Methods: PubMed and Embase were searched for studies published from inception through April 2022, evaluating the effects of the combination of GS and NSAIDs in OA patients, versus either treatment alone. Data are reported narratively. Results: Five studies were included in this review; 4 were randomized control trials and one was a prospective observational study. The duration of combination treatment was 6 to 12 weeks. The combination was compared to celecoxib in 2 studies, meloxicam in 1, etoricoxib in 1, and a conventional NSAID in 1 (ibuprofen or piroxicam). All 5 studies reported that in patients with knee OA, the combination of GS plus NSAID yielded a significantly greater benefit than single-agent therapy, in terms of outcomes including pain reduction, function, joint stiffness, and markers of inflammatory activity and cartilage degradation. Conclusion: The 5 studies included in this scoping review all report a significantly greater clinical benefit with a combination of GS plus NSAID compared to either treatment alone. The evidence supports efficacy in reducing pain, improving function, and possibly regulating joint damage. However, further randomized trials with larger sample sizes are warranted to confirm these findings. [ABSTRACT FROM AUTHOR]

Joint endoprosthetics is a treatment of choice for patients with decompensated osteoarthritis (OA), who have exhausted the possibilities of pharmacotherapy and other methods of conservative treatment. Preparation for endoprosthetics and rehabilitation after surgery usually includes measures to improve the muscle condition and local blood circulation in the joint area, and if necessary, pain management. The unique spectrum of anti-inflammatory effect of chondroprotectors based on chondroitin sulfate and glucosamine sulfate includes inhibition of NF-κB cascade, toll-like receptors, pro-inflammatory cytokines, metalloproteinases, and significantly alleviates the course of OA. Reducing the severity of OA is important for preparing for surgery, subsequent rehabilitation, and preventing the revision surgery.

This study investigated the role of a pattern of microRNA (miRNA) as possible mediators of celecoxib and prescription-grade glucosamine sulfate (GS) effects in human osteoarthritis (OA) chondrocytes. Chondrocytes were treated with celecoxib (1.85 µM) and GS (9 µM), alone or in combination, for 24 h, with or without interleukin (IL)-1β (10 ng/mL). Cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, apoptosis and reactive oxygen species (ROS) by cytometry, nitric oxide (NO) by Griess method. Gene levels of miRNA, antioxidant enzymes, nuclear factor erythroid (NRF)2, and B-cell lymphoma (BCL)2 expressions were analyzed by quantitative real time polymerase chain reaction (real time PCR). Protein expression of NRF2 and BCL2 was also detected at immunofluorescence and western blot. Celecoxib and GS, alone or in combination, significantly increased viability, reduced apoptosis, ROS and NO production and the gene expression of miR-34a, -146a, -181a, -210, in comparison to baseline and to IL-1β. The transfection with miRNA specific inhibitors significantly counteracted the IL-1β activity and potentiated the properties of celecoxib and GS on viability, apoptosis and oxidant system, through nuclear factor (NF)-κB regulation. The observed effects were enhanced when the drugs were tested in combination. Our data confirmed the synergistic anti-inflammatory and chondroprotective properties of celecoxib and GS, suggesting microRNA as possible mediators.

The aim of this study was to evaluate the effect of glucosamine sulfate on morphological changes investigated on the articular cartilage of knee joint during development of osteoarthritis in rabbits following collagenase-induced osteoarthritis. A total of 32 New Zealand White male and female rabbits were used in this study. All animals were kept in standard conditions at Research Institute of Livestock Production in Nitra. Animals were divided into 4 groups: healthy control group, osteoarthritic untreated group and two experimental groups. After collagenase-induced osteoarthritis daily oral administration of glucosamine sulfate ( 80 mg.kg-1 and 160mg.kg-1 of live weight) was performed. At the end of the eight week, the rabbits were sacrificed and their both right and left knees with proximal femur and distal tibia were harvested. Gross morphology of knee joint was tested. Basal statistical indicators were calculated from obtained data using Statgraphics software and analysis of variance. Morphological changes in osteoarthritic group without treatment were seen on both, medial and lateral region, but markedly on medial condyle. Articular cartilage was characterized by a rough and hypertrophic appearance with severe erosions. The severity of cartilage damage was generally lower in glucosamine treated groups in comparison with osteoarthritis group. The gross morphological examination of healthy control revealed very little or no changes. Gross morphological grading of cartilage damage showed significantly lower extent of damage in glucosamine treated groups.

The objective of this research was to evaluate the effect of glucosamine sulfate on histological changes of articular cartilage degeneration in rabbits. Knee joints during development of osteoarthritis in rabbits following collagenase-induced osteoarthritis were investigated. A total of 32 New Zealand White male and female rabbits were used in this study. All animals were kept in standard conditions at Research Institute of Livestock Production in Nitra. Animals were divided into 4 groups: healthy control group, osteoarthritic untreated group and two experimental groups. After collagenase-induced osteoarthritis daily oral administration of glucosamine sulfate (80 mg.kg-1 and 160 mg.kg-1 of live weight) was performed. After completion of the experiment, rabbits were subjected to euthanasia. After euthanasia, femur and fibula together were dissected for morphological and histological examination. Histopathological degeneration was assessed from histological slides. All parameters evaluated in osteoarthritic groups have specific stage of development of osteoarthritis, thickening of cartilage surface, cartilage thickness, number and distribution of chondrocytes and overall morphology. Morphological and histological evaluation of the femoral condyles in glucosamine-treated groups showed a lower extent and severity of the destruction of the cartilage in comparison with osteoarthritic control group.

Background. The complex mechanisms of action of chondroitin sulfate (CS) and glucosamine sulfate (GS) at the molecular level make it possible to assert the applicability of the corresponding drugs far beyond chondroprotection. Inhibition of proinflammatory mechanisms (NF-κB, activation of toll-receptors, increased levels of cytokines, degranulation of mast cells, etc.) by CS and GS provide the prospects for their use to inhibit inflammation in the respiratory tracts, allergic processes and to enhance the effects of glucocorticoids.Objective: to systemize data on the effects of chondroitin sulfate and glucosamine sulfate on pathophysiological processes in pulmonary pathology.Material and methods. Using the methods of the theory of text topological analysis an intellectual analysis of 1273 publications on fundamental and clinical studies of the relationship of CS and GS with lung function was carried out. The search was performed by a key query “(glucosamine OR chondroitin) AND (lung OR lungs OR pulmonary OR pulmonology)” in the Pubmed/MEDLINE database. As a result, 59 informative biomedical terms were identified.Results. The chemoproteomic study of CS and GS showed that their intake promoted an increase in the expression of 19 antitumor proteins and a decrease in the expression of 25 pro-inflammatory proteins involved in lung function. CS and GS can be used in the complex therapy of infectious diseases of the lungs, with fibrotic changes in the respiratory tracts and, as well, help to reduce the risk of neoplastic diseases of the lungs.Conclusion. The results of this analysis allow us to assert the promising nature of the use of CS and GS in several neoplastic diseases of the lungs, as well as the high safety of drugs based on pharmaceutical standardized forms of CS and GS in terms of lung function.

Background. Long-term use of chondroprotective agents – chondroitin sulfate (CS) and glucosamine sulfate (GS) in the treatment of osteoarthritis puts forward increased requirements for the safety of drugs, primarily in terms of effects on the liver and kidneys.Objective: systematization of data on the effect of chondroprotectors on liver structure and functions.Material and methods. Using the methods of the theory of topological text analysis, an intellectual analysis of 2319 publications on fundamental and clinical studies of the relationship of CS and GS with liver function was carried out. The search was performed by a key query “(chondroitine OR glucosamine) AND (liver OR hepatic OR hepatocy*)” in the PubMed/MEDLINE database.Results. The systematic analysis indicated a pronounced hepatoprotective effect of CS and GS pharmaceutical substances with a high degree of purification from inorganic and organic impurities. By regulating inflammation processes, lymphocyte function, fat and carbohydrate metabolism in the liver, standardized forms of CS and GS have a beneficial effect on fat metabolism, reduce chronic inflammation in the liver, exhibit antitumor and pronounced hepatoprotective effects on various models of liver intoxication.Conclusion. The results of this analysis allow us to assert the high safety of drugs based on pharmaceutical standardized forms of CS and GS in terms of liver function.

Of undoubted interest is the search for new drugs comparable in effectiveness to nonsteroidal anti-inflammatory drugs (NSAIDs), but with a safer application profile. NSAIDs are characterized by a good analgesic effect due to the modulation of prostaglandin metabolism by inhibition of cyclooxygenase-2. One of the promising directions of pharmacotherapy of degenerative-dystrophic joint lesions is the use of symptom-modifying drugs of delayed action, which include chondroitin sulfate (CS). CS has antiresorptive activity, anti-inflammatory and anti-inflamaging effects. In addition to the direct effect on pain syndrome severity, he also have a modulating level effect of systemic inflammation of cartilage tissue. According to experts of international and Russian societies, pharmaceutical prescription-quality CS is a basic part of the treatment of osteoarthritis. One of the advantages of CS over NSAIDs is the preservation of the effect for 24 months after the treatment. Against the background of the use of CS, it is possible to reduce the dose or completely cancel NSAIDs, which helps to reduce the frequency of adverse events associated with their intake. CS has a favorable safety profile, which is important for elderly patients and those with comorbid diseases (cardioprotective effects). CS drugs can be administered per orally, intramuscularly, intra-articularly and in combination with different administration methods. Several clinical trials of CS (Chondrogard), including randomized, were conducted in Russia. The Russia Health Ministry approved the appointment of parenteral CS in clinical guidelines: Chronic pain in elderly and senile patients (2020), Falls in elderly and senile patients(2020), "Knee osteoarthritis" (2021), "Hip osteoarthritis" (2021).

The pharmacoinformation approach to the assessment and modeling of drugs involves the use of modern methods of data mining. These methods include: 1) analysis of big data (selection of texts of scientific publications, search for new biomarkers); 2) computer analysis of texts (automatic classification of texts by content, identification of pseudoscientific texts); 3) analysis of metric maps (visualization and analysis of complex patterns, including clustering) and 4) chemoinformation analysis, including the assessment of the effect of drugs on the transcriptome, proteome and microbiome of a person. The article provides examples of the application of these methods of pharmacoinformatics to chondroprotectors containing standardized forms of chondroitin sulfate and glucosamine sulfate.

Blend nanofibres composed of synthetic polymers with biological macromolecules, such as natural biopolymers, and 3D structures created via electrospinning technique, have a high potential for modification to promote cell growth and function. In this study, 5 and 7 wt% of glucosamine sulfate (GAS), as one of the key components in the extracellular matrix (ECM) of natural cartilage tissue, were added to poly (3-hydroxybutyrate)-chitosan (PHB-CS)/functionalized multiwalled carbon nanotubes (f-MWCNTs) solution (100:20:1) for production of electrospun scaffolds. Prepared fibrous scaffolds are characterized by SEM, FTIR, XRD, TGA, and DSC. Tensile tests are used to study their mechanical properties and their hydrophilicity is also assessed. subsequently, the drug release profile of the scaffolds, adipose stem cell proliferation, cell viability, and the differentiation of adipose stem cells to chondrocyte cells were evaluated for further cartilage tissue engineering application. Our results showed that the addition GAS has a positive effect on the hydrophilicity of the fibers and the initiation of chondrogenic differentiation. Without, effects on tensile strength of the scaffolds by adding 5%. So, that PHB-CS/f-MWCNTs scaffold containing GAS has more acceptable properties than the PHB or PHB-CS for cartilage tissue engineering. [ABSTRACT FROM AUTHOR]

Toll-like receptors (TLRs) act as receptors for bacterial lipopolysaccharides (LPS) and participate in innate immunity. Excessive TLRs activity leads to chronic inflammation and the development of several comorbid pathologies, including osteoarthritis (OA). Computer analysis of 52,312 publications devoted to TLRs was made to systematically describe the mechanisms of biological action of TLRs and their influence on the OA pathophysiology. In addition, we identified the mechanisms by which slow-acting drugs based on standardized forms of chondroitin sulfate (CS), which have symptom-modifying and structural-modifying effects, can decrease TLRs activity and be used in the treatment of OA. Our conclusions are supported by the results of TLRs chemoreactom analysis, as well as by clinical and experimental data.

AIM: Glucosamine derivatives have been found to have anticancer effects in many cancer cell lines in previous investigations. The effect of glucosamine sulfate on neuroblastoma, however, is uncertain. The potential cytotoxic effects of glucosamine sulfate on the SH-SY5Y cell line were investigated in this study. The underlying mechanisms of this cytotoxicity have also been studied. MATERIAL AND METHODS: In this study, the SH-SY5Y cell lines were used. The cells were treated with various concentrations of glucosamine sulfate (0.3125, 0.625, 1.25 and 2.5 µg/mL) and the viability of the cells was determined using the XTT assay after 24 hours. The quantities of cleaved PARP, BCL-2, 8-Hydroxy-desoxyguanosine (8-oxo-dG), cleaved caspase 3, Bax, total oxidant, and total antioxidant in the cells were determined by ELISA kits. RESULTS: At doses of 0.3125, 0.625, 1.25 and 2.5 µg/mL, glucosamine sulfate dramatically reduced cell viability in SH-SY5Y cells (p<0.001). ELISA tests demonstrated that 1.25 µg/mL glucosamine sulfate considerably increased the amounts of 8-oxo-dG, cleaved caspase 3, Bax, cleaved PARP and total oxidant. However, 1.25 µg/mL glucosamine sulfate treatment did not change the quantity of BCL-2 protein. CONCLUSIONS: Altogether, glucosamine sulfate produced considerable cytotoxicity in SH-SY5Y cells by triggering oxidative stress, inducing DNA damage, and finally causing apoptosis. In addition, more research is needed to determine the efficacy of glucosamine sulfate as an anticancer drug in the treatment of neuroblastoma (Fig. 5, Ref. 39). Text in PDF www.elis.sk [ABSTRACT FROM AUTHOR]

A systematic analysis of 37 post-genomic osteoarthritis (OA) studies (genomics, transcriptomics, proteomics, metabolomics) allowed to isolate 483 genes and corresponding proteins, their levels and activity disturbances are involved in the pathogenesis of the disease. These proteins can be conditionally subdivided into three groups: 1) structural proteins of connective tissue (CT); 2) proteins that support the activity of CT growth factors; 3) proteins that promote CT remodeling and degradation, as well as proteins associated with the regulation of inflammation (cellular response to tumor necrosis factor α, interleukin 1, bacterial lipopolysaccharides, NF-κB activation, etc.). It is important to note the epigenetic effects (DNA hypomethylation) associated with the pathogenesis of OA, which indicates the need for the use of vitamins group B in the therapy. Chondroprotectors (symptomatic slow-acting drugs) – chondroitin sulfate (CS) and glucosamine sulfate (GS), – in addition to reducing inflammation through inhibition of NF-κB and lipopolysaccharide receptors (Toll-receptors), also contribute to an increase in the expression of genes for structural CT proteins, CT growth factors and modulate the activity of CT remodeling and degradation proteins. These effects of CS/GS allowed to describe the complex mechanisms of the pathogenetic action of CS/GS in the treatment of OA.

The article focuses on the review of a pharmacotherapeutic approach to the therapy of hand osteoarthritis (HO). Apart from non-steroid antiinflammatory drugs (NSAID), promising therapeutic means of HO therapy include steroid drugs, chondroitin sulfate (CS), glucosamine sulfate (GS), and vitamin D. Transdermal application of NSAID and steroid drugs reduces the side effects without a decrease in the effectiveness of the therapy. Reconstructive therapy of cartilaginous and connective tissue of hands includes a long-term application of CS/GS, and in the acute period, injections of CS/GS.

Chronic pain (CP) is still one of the urgent problems of modern medicine. The paper provides a review of the main pharmacotherapeutic approaches from the standpoint of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) guidelines. When preparing this material, the authors have analyzed the publications available in the resources: PubMed, EMBASE, Cochrane, and еLIBRARY. The paper presents the main pathogenetic mechanisms of pain syndrome development in osteoarthritis (OA), including synovial inflammation and associated immune disorders. It considers the types of development of pain syndrome and the main prognostic outcomes according the mechanism of pain, providing a rationale for the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and/or chondroprotectors (CPs). In accordance with the ESCEO guidelines, it is noted that when starting OA therapy, CPs should be considered as the first step (in their long-term prescription and pharmaceutical quality), then NSAIDs should be added (topically), then (if ineffective) orally, by excluding patients with hip OA. It is known that the intramuscular administration of CPs (chondroitin sulfate (CS) in particular) can increase their bioavailability. The use of glucosamine sulfate (GS) is recommended for patients over 60 years of age. According to the recommendations of the 2019 ESCEO experts, CS and GS should be used as a disease-modifying OA drug from the first step and at all subsequent stages.

Introduction. The pharmaceutical drugs used in the treatment of osteoarthritis (OA) differ not only in the mechanisms of anti-inflammatory action but also in the effects on the human microbiome.Purpose. Evaluation of the influence of some drugs used in the therapy of OA on the human microbiome by the method of chemoinformation analysis.Materials and methods. Сomparative chemomicrobiome analysis of glucosamine sulfate (GS), diclofenac, acetylsalicylic acid (ASA), and three prebiotics (lactose, lactulose, fructose) as molecules of comparison. For each substance, estimates of the area under the curve (AUC) were obtained for a representative sampling of human microbiota (38 commensal bacteria). The minimum inhibitory concentrations (MIC) were established for more than 120 pathogenic bacteria.Results. On average, according to a representative sampling of microbiota, the profile of the action of GS on the microbiome was almost identical to the profile of the action of lactose (AUC=0.23±0.18). The most effective growth of the microbiome was provided by fructose and lactulose (AUC=0.58±0.21). The effects of diclofenac and ASA on the commensals of microbiome were comparable to the effects of GS (AUC=0.27±0.22). However, the analysis of the obtained MIC values for pathogenic bacteria showed that diclofenac supported the growth of the pathogenic flora (MIC=35±1.4 μg/ml) to a greater extent than GS (MIC=16±1.5 μg/ml) and ASA (MIC=23±2.2 μg/ml).Conclusion. The effects of GS on the microbiome are comparable to the effects of the prebiotic lactose whereas the inhibitory effect of GS and ASA on pathogenic bacteria is more pronounced than that of diclofenac. The inhibition of pathogenic bacteria by the GS helps to reduce inflammation.

Chondroitin sulfate (CS) and glucosamine sulfate (GS) are used in the treatment of osteoarthritis and exhibit a pronounced anti-inflammatory effect. CS/GS inhibit the NF-kB signaling cascade, which realizes the biological effects of tumor necrosis factor (TNFa). Excessive activity of NF-kB also stimulates the development of atherosclerosis. The results of experimental and clinical studies show that inhibition of NF-kB by CS/GS will inhibit the formation and growth of atherosclerotic plaques also reducing levels of other markers of inflammation.

The chondroprotectors glucosamine sulfate (GS) and chondroitin sulfate (CS) show a complex anti-inflammatory effect and therefore may be used in the therapy of many diseases concurrent with osteoarthritis.Objective: to carry out a systematic analysis of the relationship between the molecular pathophysiology of tenosynovitis and the potential mechanisms of pathogenic action of CS/GS in this disease.Material and methods. The texts of 15 097 publications were systemized using the current methods for topographic big data analysis, which had been developed as part of topological and metric approaches to recognition/classification problems.Results and discussion. The investigators created a map showing the molecular pathophysiology of tendosynovitis and including 15 molecular mechanisms and 27 comorbidities and identified mechanisms, through which GS/CS could prevent the development of tenosynovitis, such as inhibition of the effects of proinflammatory cytokines (IL-1, IL-8, γ-interferon, and TNF-α), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein, NLRP3 inflammasome, NF-κB and JAK/STAT signaling pathways, and O-glucosamination of proteome proteins. To date, no randomized clinical or cohort (non-interventional) studies of the effects of CS/GS have been conducted in patients with tendosynovitis and comorbidities. However, preclinical studies of GS and CS in the treatment of tendinopathies showed that the drugs had analgesic properties, alleviated chronic inflammation and edema, and improved the maturation of collagen bundles and therefore the mechanical properties of connective tissue in the tendons and ligaments.Conclusion. The experimental and clinical studies indicate that pharmaceutical-grade GS/CS preparations of high standardization are promising in treating tenosynovitis.

Abstract Purpose To evaluate the repairing effects of glucosamine sulfate combined with etoricoxib on articular cartilages of patients with knee osteoarthritis (KOA). Methods A total of 106 KOA patients were randomly divided into control (n = 40) and experimental groups (n = 66) and treated with etoricoxib alone and glucosamine sulfate plus etoricoxib, respectively. Changes in WOMAC score and clinical efficacy were observed. The synovial fluid was extracted. Bone metabolism indices, growth factors, inflammatory factors, matrix metalloproteinases (MMPs), and NO-induced apoptosis-related factors were measured by ELISA. JNK and Wnt5a mRNA levels were determined using RT-PCR. Results After treatment, the total WOMAC scores of both groups significantly declined (P < 0.05), being lower in experimental group. The total effective rate of experimental group was higher (P < 0.05). BGP and OPG levels rose, especially in experimental group (P < 0.05). CTX-II, COMP, and RANKL levels decreased, particularly in experimental group (P < 0.05). TGF-β, IGF-1, and FGF-2 levels increased, especially in experimental group (P < 0.05). Both groups, particularly experimental group, had decreased levels of IL-1β, IL-17, IL-18, TNF-α, MMP-3, MMP-9, and MMP-13 (P < 0.05). JNK and Wnt5a mRNA levels of both groups dropped, which were lower in experimental group (P < 0.05). NO and LPO levels reduced, being lower in experimental group. SOD level rose, especially in experimental group (P < 0.05). Conclusion Glucosamine sulfate plus etoricoxib can repair the articular cartilages of KOA patients. Probably, JNK and Wnt5a are downregulated to inhibit the secretion of MMPs through lowering the levels of inflammatory factors, thereby delaying cartilage matrix degradation. NO-induced chondrocyte apoptosis may be suppressed via the SOD pathway.

Introduction. Chondroitin sulfate (CS) and glucosamine sulfate (GS), widely used as chondroprotectors, can maintain the normal functioning of the urinary system but their effect has not been analyzed systematically.Aim: to perform a systematic analysis of the possibilities of using CS and GS in patients with pathology of the kidneys and urinary system.Materials and methods. Predictive analysis of 2,093 publications on the interactions of CS/GS with the functioning of the kidneys and other organs of the urinary system found at the request “(urinary OR bladder OR kidney) AND (glucosamine OR chondroitin)” by methods of the theory of topological data analysis.Results. Disorders of cholesterol and glucosamine metabolism are characteristic of cystitis, glomerular nephritis, urinary tract infections (UTIs), urolithiasis, proteinuria, and formation of diabetic nephropathy. In addition to inhibiting the pro-inflammatory cascade NF-kB, CS/GS contribute to eliminating the deficiency of glycosaminoglycans in the pathology of urothelium, inhibit urolithiasis, inhibit the synthesis of pro-inflammatory nitric oxide NO in macrophages, and modulate O-glycosylation processes.Conclusion. The results of fundamental and clinical studies show that subsidies of CS/GS substances of pharmacological quality per os and CS instillation in the bladder (in particular, in combination with hyaluronic acid) are the means of choice for patients suffering from osteoarthritis and diseases of the urinary system. Highly purified pharmacological CS substances are part of the preparation Chondroguard.

Background: Recent trends suggest using novel host-modulating agents as a treatment strategy for chronic periodontitis. Glucosamine sulfate (GS) was proven to have anti-inflammatory actions related to its ability to suppress neutrophil functions. Orthoboon, an anti-arthritic and anti-inflammatory drug, has shown to have a positive therapeutic effect due to its constituents made of a combination of GS, Vitamin C, and collagen. The aim of the study was to evaluate the host modulatory effects of Orthoboon on periodontal status and to estimate the C reactive protein (CRP) levels before and after nonsurgical periodontal therapy (NSPT). Materials and Methods: A total number of 40 patients with chronic periodontitis were randomly divided into two groups of 20 patients each. The test group patients (n = 20) received 500 mg Orthoboon three times daily for 45 days. Prior to the initiation of Orthoboon, all patients in both test group and control group were subjected to Phase I periodontal therapy. CRP levels were estimated immediately after phase I therapy and 45 days after therapy. Clinical parameters including plaque index, gingival index, and bleeding index were recorded before and after NSPT for the two groups. Results: The mean CRP levels were reduced significantly in the test group before and after administration of Orthoboon and also there were statistically significant differences in the mean CRP levels at the end of 45 days between the test group and the control group. Conclusion: Administration of Orthoboon, i.e., GS, with a combination of Vitamin C and collagen was proved to be of a significant benefit in the test group than in the control group.

The aim of this study was to develop a topically applied formulation with the potential to alleviate arthritis ailments. A combination of two active ingredients, icariin from Epimedium L. (Species: Epimedium Koreanum) extract as a potential promoter of chondrogenesis and glucosamine sulfate as a precursor of cartilage tissues, was tested. In permeation studies, the potential for skin permeation of both substances was confirmed; however, the in vitro release test did not accurately reflect the degree of skin permeation. The in vitro release of icariin was at a level of 15.0–19.0% for the plant-extract-derived icariin and 29.0–35.0% for the pure substance. The level of glucosamine sulfate release was 38.4% (on average). For icariin of both origins, the release results were higher than those obtained via oral administration (about 12.0%), which shows the potential superiority of topical application. In addition, the physicochemical parameters that affect the in vitro release and performance of topical formulations were addressed. This preliminary research and permeation analysis of the formulation produced a promising picture of its prospects regarding arthritis treatment, although further investigation is needed.

Aging is an independent risk factor for the development of many diseases and geriatric syndromes. Osteoarthritis (OA), as the most common joint disease in the elderly, can be attributed to age - associated conditions. And the most significant geriatric syndrome, which dramatically affects the management and prognosis of an elderly, is frailty. The review provides current information on the prevalence of OA and frailty, their clinical and prognostic significance, and also shows the mutually aggravating role of these two conditions. The difference between non - and medication management of patients with OA and frailty is emphasized.

Background. So-called rational drug design is suboptimal when it comes to finding effective and safe drug-based treatment for COVID-19. Another approach seems promising: to reprofile the pharmaceuticals registered in the Anatomical, Therapeutic, and Chemical Classifier (ATC).Material and methods. Chemoreactome screening, a method that simulates the results of inhibiting viral growth in a cell culture, models the effects of pharmaceuticals on the human virome, and estimates the adverse effects of medicines, was used to reprofile about 2700 pharmaceuticals from the ATC. The information technology behind chemoreactome analysis is based on the topological recognition theory advanced by the Institute of Pharmaceutical Informatics, Federal Research Center for Informatics and Control, Russian Academy of Sciences.Results. Sixty two pharmaceuticals and 20 micronutrients were found to have a pronounced antiviral effect with minimal side effects. Comparison against data of basic research and clinical trials showed 31 out of 62 pharmaceuticals to have been independently confirmed usable in COVID-19 treatment. These inhibit coronaviral proteins and/or function as adaptogenic molecules that improve the functioning of cells exposed to viral stress. Glucosamine sulfate was found to have the best safety profile and minimum effects on the healthy human virome out of all the tested anticoronaviral micronutrients.Conclusions. Reprofiling of pharmaceuticals registered in the ATC could significantly speed up the search for more effective and safer drugbased COVID-19 treatments. Several micronutrients show promise for long-term coronavirus prevention, especially in the elderly.

Osteoarthritis (OA) is a widespread disease accompanied by persistent joint damage with obvious functional failure, which leads to early disability in patients. In OA, different groups of joints are involved in the pathological process. Hand joints are one of the classical sites of OA. The paper discusses the role of mechanical load, genetic factors, and sex hormone deficiency in the development of the disease. The treatment policy includes a set of non-pharmacological, pharmacological, and surgical methods.

ABSTRACT The effect of different nitrogen sources (glucosamine sulfate, ammonium sulfate, aspartic acid, phenylalanine and peptone) in comparison to sodium nitrate, the major nitrogen compound in basal agar Czapek’s synthetic medium growth were studied on the linear growth of Rhizoctonia solani and its pathogenicity on faba bean germinated seeds. Ammonium sulfate exhibited faster liner growth and showed the same effect as the basal medium with sodium nitrate while, glucosamine sulfate showed less growth rate compared with sodium nitrate. Glucosamine sulfate and ammonium sulfate showed significant reduction in number of infection cushions which led to significant decrease of disease index in vitro. Our results showed strongly significant positive correlations between disease index and both of diameters of hyphae and number of infection cushions while, very weak correlation coefficient was found between disease index and linear growth of R. solani. Under greenhouse conditions, glucosamine sulfate or peptone as a sole nitrogen sources in food requirements of Rhizoctonia solani inoculum depressed the virulence of the fungus. The effect of different amounts of glucosamine sulfate was determined on fungal growth rate, infection cushions, disease index in vitro and polyphenol oxidase activity. Increasing amount of glucosamine sulfate showed significantly reduction of growth rate in comparison to the basal medium with sodium nitrate. All seeds subjected to R. solani grown on different amount of glucosamine sulfate showed the lower number of infection cushions, disease index and polyphenol oxidase activity compared with sodium nitrate. Under greenhouse conditions, disease index showed significantly decreased effect when glucosamine sulfate used as soil applications and showed better effect on shoot weight and root weight compared with control plants treated with sodium nitrate. Our study proposes that glucosamine sulfate may acts as controlling factor of pathogenicity genes of R. solani. Key words: Rhizoctonia solani, faba bean, Vicia faba, nitrogen sources, glucosamine sulfate, pathogenicity.