Fibroblast growth factor 21 (FGF21) plays a crucial role in metabolism and brain function. Glucosamine (GLN) has been recognized for its diverse beneficial effects. This study aimed to elucidate the modulation of FGF21 production by GLN and its impact on learning and memory functions. Using both in vivo and in vitro models, we investigated the effects of GLN on mice fed with a normal diet or high-fat diet and on mouse HT22 hippocampal cells, STHdhQ7/Q7 striatal cells, and rat primary cortical neurons challenged with GLN. Our results indicated that GLN promotes learning and memory functions in mice and upregulates FGF21 expression in the hippocampus, cortex, and striatum, as well as in HT22 cells, STHdhQ7/Q7 cells, and cortical neurons. In animals receiving GLN together with an FGF21 receptor FGFR1 inhibitor (PD173074), the GLN-enhanced learning and memory functions and induction of FGF21 production in the hippocampus were significantly attenuated. While exploring the underlying molecular mechanisms, the potential involvement of NF-κB, Akt, p38, JNK, PKA, and PPARα in HT22 and NF-κB, Akt, p38, and PPARα in STHdhQ7/Q7 were noted; GLN was able to mediate the activation of p65, Akt, p38, and CREB in HT22 and p65, Akt, and p38 in STHdhQ7/Q7 cells. Our accumulated findings suggest that GLN may increase learning and memory functions by inducing FGF21 production in the brain. This induction appears to be mediated, at least in part, through GLN’s activation of the NF-κB, Akt, p38, and PKA/CREB pathways.

Alcohol liver disease (ALD) is a liver disease caused by long-term heavy drinking. Glucosamine (GLC) is an amino monosaccharide that plays a very impo…

Glucosamine hydrochloride (GAH) is a natural component of glycoproteins present in almost all human tissues and participates in the construction of human tissues and cell membranes. GAH has a wide range of biological activities, particularly in anti-inflammatory and osteogenic damage repair. At present, little is known about how GAH functions in angiogenesis. To determine the role of GAH on vascular development and impairment repair, we used the inhibitors VRI, DMH1, and dorsomorphin (DM) to construct vascular-impaired models in Tg(kdrl: mCherry) transgenic zebrafish. We then treated with GAH and measured its repair effects on vascular impairment through fluorescence intensity, mRNA, and protein expression levels of vascular-specific markers. Our results indicate that GAH promotes vascular development and repairs impairment by regulating the vascular endothelial growth factor (VEGF) signaling pathway through modulation of bone morphogenetic protein (BMP) signaling. This study provides an experimental basis for the development of GAH as a drug to repair vascular diseases.

Anti-Inflammatory Properties of Glucosamine Used in Combination with Plants Extracts on Adjuvant Arthritis Rat. PubMed, SCI, Scopus, ESCI, PMC indexed

Radiotherapy is a very important tool in the treatment of cancer; nevertheless, its side effects are a hindrance to its use. The present study is designed to ev...

Osteoarthritis (OA) is one of the major joint diseases, and the synovial inflammation is involved in the pathogenesis and progression of OA. Glucosamine (GlcN) is widely used as a dietary supplement for OA, and is expected to exert the antiinflammatory action in OA. However, the detailed mechanism for the antiinflammatory action of GlcN remains poorly understood. In this study, to elucidate the molecular mechanism involved in the GlcN-medicated regulation of synovial cell activation, we comprehensively analyzed the effect of GlcN on the gene expression using a human synovial cell line MH7A by DNA microarray. The results indicated that GlcN significantly downregulates the expression of 187 genes (≤1/1.5-fold) and upregulates the expression of 194 genes (≥1.5-fold) in IL-1β-stimulated MH7A cells. Interestingly, pathway analysis indicated that among the 10 pathways into which the GlcN-regulated genes are categorized, the 4 pathways are immune-related. Furthermore, GlcN suppressed the expression of proinflammatory cytokine genes (such as IL-6, IL-8, IL-24 and TNF-α genes). In addition, GlcN-mediated O-GlcNAc modification was involved in the downregulation of TNF-α and IL-8 genes but not IL-6 and IL-24 genes, based on the effects of alloxan, an O-GlcNAc transferase inhibitor. Thus, GlcN likely exerts an antiinflammatroy action in OA by suppressing the expression of proinflammatory cytokine genes in synovial MH7A cells by O-GlcNAc modification-dependent and -independent mechanisms.

Osteoarthritis is a degenerative disease that causes substantial changes in joint tissues, such as cartilage degeneration and subchondral bone sclerosis. Chondroitin sulfate and glucosamine are commonly used products for the symptomatic treatment of osteoarthritis. The aim of the present study was to investigate the effects of these products when used as structure-modifying drugs on the progression of osteoarthritis in the rabbit temporomandibular joint. Thirty-six New Zealand rabbits were divided into 3 groups (n = 12/group): control (no disease); osteoarthritis (disease induction); and treatment (disease induction and administration of chondroitin sulfate and glucosamine). Osteoarthritis was induced by intra-articular injection of monosodium iodoacetate. Animals were killed at 30 and 90 days after initiation of therapy. The treatment was effective in reducing disease severity, with late effects and changes in the concentration of glycosaminoglycans in the articular disc. The results indicate that chondroitin sulfate and glucosamine may have a structure-modifying effect on the tissues of rabbit temporomandibular joints altered by osteoarthritis.

About Authors: Priya M. Padalia*, Manthan A. Padalia Dagon Pharmaceuticals Pvt. Ltd. *modiyapriya@gmail.com

Author summary Cryptococcal meningitis claims half a million lives each year. There is no clinically available vaccine and the current antifungal therapies have serious limitations. Thus identifying cryptococcal specific programs that can be targeted for antifungal or vaccine development is of great value. We have shown previously that switching from the yeast to the hypha form drastically attenuates/abolishes cryptococcal virulence. Cryptococcal cells in the filamentous form also trigger host immune responses that can protect the host from a subsequent lethal challenge. However, self-filamentation is rarely observed in serotype A isolates that are responsible for the vast majority of cryptococcosis cases. In this study, we found that glucosamine stimulated self-filamentation in genetically distinct strains of the Cryptococcus species complex, including the most commonly used serotype A reference strain H99. We demonstrated that filamentation elicited by glucosamine did not depend on the pheromone pathway, but it requires the calcineurin transcription factor Crz1. Glucosamine promotes nuclear translocation of Crz1, which is positively controlled by the phosphatase calcineurin and is suppressed by the HOG pathway. These findings raise the possibility of manipulating genetic pathways controlling fungal morphogenesis against diseases caused by the Cryptococcus species complex.

Glucosamine (GlcN) is a naturally occurring derivative of glucose and an over-the-counter food additive. However, the mechanism underlying GlcN action on cells is unknown. In this study, we investigated the effect of GlcN on natural killer (NK) cells. We demonstrate that GlcN affects NK-92 cell cytotoxicity by altering the distribution of cathepsin C, a cysteine protease required for granzyme processing in cytotoxic granules. The relocation of cathepsin C due to GlcN was shown to be accompanied by a decrease in the intracellular enzyme activity and its extracellular secretion. Similarly, the relocation of endosomal aspartic cathepsin E was observed. Furthermore, we elucidated that repositioning of cathepsin C is a consequence of altered signaling pathways of cytotoxic granule movement. The inhibition of phosphorylation upstream and downstream of ERK by GlcN disturbed the polarized release of cytotoxic vesicles. Considerable changes in the ERK phosphorylation dynamics, but not in those of p38 kinase or JNK, were observed in the IL2-activated NK-92 cells. We found decreased phosphorylation of the transcription factor FOXO1 and simultaneous prolonged phosphorylation of ERK as well as its nuclear translocation. Additionally, a protein downstream of the ERK phosphorylation cascade, paxillin, was less phosphorylated, resulting in a diffuse distribution of cytotoxic granules. Taken together, our results suggest that dietary GlcN affects signaling pathway activation of NK-92 immune cells.

To assess the association of different sedentary behaviors and glucosamine use with the risk of kidney stones and examine the modification of genetic …

Background The relationship of glucosamine use with incident dementia in the older population remains uncertain. We aimed to evaluate the longitudinal association between habitual glucosamine supplement and the risk of cause-specific dementia and examine the possible effect modifiers on this association. Methods The study included 214,945 participants over the age of 60 who had available information on glucosamine use and did not have dementia at baseline in the UK Biobank. The APOE genotypes were determined by a combination variant of rs429358 and rs7412. The primary outcome was incident vascular dementia, incident Alzheimer’s disease, and incident frontotemporal dementia, respectively. Results Over a median follow-up duration of 12 years, 1039, 1774, and 122 participants developed vascular dementia, Alzheimer’s disease, and frontotemporal dementia, respectively. Overall, habitual glucosamine use was significantly associated with a lower risk of incident vascular dementia (adjusted HR, 0.82; 95%CI, 0.70–0.96), but not significantly associated with incident Alzheimer’s disease (adjusted HR, 1.02; 95%CI, 0.92–1.14) and incident frontotemporal dementia (adjusted HR, 0.95; 95%CI, 0.63–1.43). Moreover, the inverse association between habitual glucosamine use and incident vascular dementia was more pronounced in participants with concomitant supplement of calcium (P-interaction = 0.011), and those without concomitant supplement of zinc (P-interaction = 0.018). However, APOE ε4 dosage and baseline cognitive function did not significantly modify the relationships of glucosamine use with incident vascular dementia or Alzheimer’s disease (All P-interactions > 0.05). Conclusions Regardless of APOE genotypes and baseline cognitive function, habitual glucosamine use was significantly inversely associated with incident vascular dementia in the older population.

Glucosamine hydrochloride (GAH) is a kind of natural hexose, which is used to promote the synthesis of mucopolysaccharides and improve the metabolism of articular cartilage. In this paper, the solubility of GAH in pure water and aqueous system with the presence of three kinds of additives (HCl, NaCl, KCl) at temperatures ranging from 278.15 K to 323.15 K was determined by gravimetric method. When there are additives in water, the solubility of GAH increases with the increase of temperature and decreases with the increase of concentration of the three kinds of additives. When the additives were at similar mole fractions, HCl led to the lowest solubility of GAH. The modified Apelblat model and van’t Hoff model were used to correlate the solubility data. The average relative deviation (ARD) data of Apelblat and van’t Hoff models were less than 5%, indicating good fitting results. Based on the thermodynamic data, the cooling crystallization process of GAH was performed. It was found that the additives could affect the crystal morphology, particle size, and yield of GAH products. This study supplemented the thermodynamic data of GAH and studied the cooling crystallization process in the presence of GAH additives, which provided important guidance for the optimization of the crystallization process.

Glucosamine hydrochloride (GAH) is a marine biological preparation derived from natural chitin and improves articular cartilage metabolism. In this st…

To evaluate the association between regular glucosamine intake and heart failure (HF) and to explore whether the association is mediated by relevant c…

Kidney fibrosis is closely associated with the progression of chronic kidney disease (CKD). Furthermore, copper-containing secretory amine oxidases, such as lysyl oxidase (LOX) and LOX-like 1-4 (LOXL1-4), play pivotal roles in the regulation of extracellular components and facilitate fibrosis. In th …

Background To investigate the ameliorative effects of glucosamine (GS), chondroitin sulphate (CS) and glucosamine plus chondroitin sulphate (GC) on rheumatoid arthritis (RA) in rats, and to explore the mechanism of GS, CS and GC in improving RA based on the gut microbiota. Methods RA rat models were effectively developed 14 days after CFA injection, and then garaged with GS, CS and GC. Body weight and paw volume of rats were monitored at multiple time points at the beginning of CFA injection. Until D36, serum and ankle tissue specimens were used to measure levels of circulating inflammatory factors (TNF-α, IL-1β, MMP-3, NO and PGE2) and local inflammatory indicators (TLR-4 and NF-κB). On D18, D25, and D36, intergroup gut microbiota was compared using 16S rRNA gene sequencing and bioinformatics analysis. We also performed the correlation analysis of gut bacteria, joint swelling and inflammatory indicators. Results GC, rather than GS and CS, could reduce right paw volumes, levels of TLR-4 and NF-κB in synovial tissues. In addition, enriched genera in RA model rats screened out by LEfSe analysis could be inhibited by GC intervention, including potential LPS-producing bacteria (Enterobacter, Bacteroides, Erysipelotrichaceae_unclassified and Erysipelotrichaceae_uncultured) and some other opportunistic pathogens (Esherichia_Shigella, Nosocomiicoccus, NK4A214_group, Odoribacter, Corynebacterium and Candidatus_Saccharimonas.etc.) that positively correlated with pro-inflammatory cytokines, right paw volume, and pathology scores. Furthermore, the gut microbiota dysbiosis was observed to recover before alleviating joint swelling after interventions. Conclusions GC could inhibit potential LPS-producing bacteria and the activation of TLR-4/NF-κB pathway in RA rats, thus alleviating RA-induced joint injury.

Purpose: SYSADOAs (symptomatic slow-acting drugs for osteoarthritis) are a heterogeneous group of drugs that have the ability to modify the symptoms of osteoarthritis (OA) slowly and independently of NSAIDs, analgesics or any other therapeutic option. The main drugs included in this group are glucosamine (sulphate or hydrochloride) (GS) and chondroitin sulphate (CS), widely prescribed for the treatment of OA in some countries. Although the efficacy of GS and CS for the treatment of OA remains controversial, several human, animal and laboratory studies have suggested that both drugs show anti-inflammatory properties that could reduce the risk of several diseases.

To evaluate the efficacy and safety of chondroitin sulfate and/or glucosamine hydrochloride in alleviating symptoms and improving the dysfunction of Kashin-Beck disease (KBD) patients.

Recognizing the composition and modulation of the microbiome, a viable therapeutic tool for multi-targeted therapy is a new strategy that has recently been explored. Glucosamine (GS) is being studied for its prebiotic potential in addition to being the most abundant and naturally occurring amino monosaccharide. The current study focuses on glucosamine’s prebiotic potential by assessing the stability of various GS concentrations (1% - 5%) in the gastrointestinal tract (GIT) and its ability to be fermented by the gut microbiota. The results showed that GS stimulated the most growth in L. acidophilus even after a longer incubation time than B. bifidum and L. acidophilus growth was concentration-dependent, with maximum growth at 3% with a simultaneous decrease in pH (5.6 - 1.7). The decrease in GS concentration with time also represented the growth of bacterial species, demonstrating the species’ utilization of GS. Furthermore, at 3%, GS also represented the prebiotic index of 1.9. In addition, the concentration of GS in various simulated GIT fluids was estimated in both fast and fed conditions to examine GS stability at various levels in the gut. The results showed that GS remained unaffected and non-digestible in all of the simulated GIT fluids (salivary, gastric, intestinal, and colonic), but there was a slight decrease in GS concentration (2.8%) in the fasted state of gastric fluid due to low pH levels (1.6). As a result, the findings are conclusive and suggest that GS possesses prebiotic properties.

The anti-inflammatory properties of glucosamine and chondroitin suggest that they may have potential effects in cancer prevention. We performed this meta-analysis to assess the protective function ...

Background Growing evidence has showed an association between habitual glucosamine use and type 2 diabetes (T2D). However, the effect of habitual glucosamine use on risk of dementia remains poorly understood. Our study aimed to examine the association between glucosamine use and risk of dementia and further to identify the mediating role of T2D in the association. Methods A total of 495,942 participants from UK Biobank who completed a questionnaire on habitual glucosamine use were included at baseline (2006–2010) and then followed up for incidence of dementia until 2020. Cox proportional hazard regressions were performed to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident dementia. Markov multi-state models were used to explore the role of incidence of T2D during the follow-up in the association. Results Overall, 18.80% of the participants reported habitual use of glucosamine at baseline. A total of 6831 dementia events were recorded during a median follow-up of 11 years. In fully adjusted models, habitual glucosamine use was associated with a significantly lower risk of dementia (HR = 0.87, 95% CI: 0.82–0.93). Multi-state models showed that the association between glucosamine use and dementia was mediated by the incidence of T2D during the follow-up (HR of dementia without T2D: 0.92, 95% CI: 0.86–0.99; HR of post-T2D dementia: 0.79, 95% CI: 0.67–0.93). Conclusions Our findings reveal that habitual use of glucosamine supplement is associated with a lower risk of dementia, which might be explained by incidence of T2D.

Objective: The level of precursors involved in the biosynthesis of glycosaminoglycan (GAG), glucosamine synthase, and N-acetyl glucosamine (NAG), are significantly reduced in inflammatory bowel dis...

Clinical Efficacy of Glucosamine plus Sodium Hyaluronate for Osteoporosis Complicated by Knee Osteoarthritis and Its Influence on Joint Function and Bone Metabolic Markers: Background. Osteoporosis (OP) associated with knee osteoarthritis (KOA) is common in older men and postmenopausal women, and it is important to find reliable and effective treatments for this disease to improve joint function and bone metabolism in this population. Objective. To clarify the clinical efficacy of glucosamine (GlcN) plus sodium hyaluronate (SH) for OP complicated by KOA (OP + KOA) and its influence on joint function and bone metabolic markers (BMMs). Methods. Admitted from July 2019 to July 2021, 126 patients with OP + KOA were selected, including 76 cases (observation group) treated with GlcN plus SH and 50 cases (control group) given GlcN alone. The pain, joint function, BMMs, and clinical efficacy were evaluated and compared. Pain and joint function assessments employed the Visual Analogue Scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) plus Lysholm Knee Scoring Scale, respectively. BMMs mainly measured bone gla protein (BGP), serum tartrate-resistant acid phosphatase variant (TRACP)-5b, type I collagen cross-linked C-telopeptide (CTX-1), and bone-specific alkaline phosphatase (BALP). Results. Higher posttreatment VAS scores were determined in observation group as compared to control group; observation group showed lower WOMAC scores of joint function and higher Lysholm scores than control group; in terms of BMMs, TRACP-5b and CTX-1 were lower while BGP and BALP were higher in observation group; the curative effect was also higher in observation group. All the above differences were statistically significant. Conclusions. GlcN plus SH has definite clinical efficacy in the treatment of OP + KOA, which can not only significantly improve patients’ joint function and bone metabolism but also relieve pain, with high clinical popularization value.

Glucosamine, an amino-polysaccharide, has been widely used for alleviating osteoarthritis. . In the present study, attempts have been made to evaluate the potential role of glucosamine, a caloric r...

Objective. To assess the application value of comprehensive rehabilitation therapy plus glucosamine hydrochloride for exercise-induced knee injuries and its effect on knee function. Methods. A total of 96 patients with an exercise-induced knee injury who were admitted to our hospital from February 2019 to February 202 were recruited and assigned at a ratio of 1 : 1 with matched general information to a control group (n = 45) or an experimental group (n = 51). Both groups of patients received comprehensive rehabilitation therapy, and the patients in the experimental group were daily given additional glucosamine hydrochloride tablets for 8 weeks. Results. The experimental group showed a higher treatment efficacy than the control group (). After the treatment, the VAS scores and C-reactive protein of the two groups showed a decline, with a lower result in the experimental group than in the control group (). The Lysholm knee scores were increased in the two groups after the treatment, and the experimental group had a higher score (). After the treatment, patients of both groups showed reduced five-times-sit-to-stand-test (FTSST) results, with a better outcome obtained in the experimental group (). Conclusion. Comprehensive rehabilitation therapy plus glucosamine hydrochloride effectively improves the clinical efficacy of exercise-induced knee joint injuries and enhances the knee joint rehabilitation of the patients.

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 ...