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We have previously reported an application of lower range of molecular weight of xanthan gum (LRWXG) for inhibiting cartilage matrix destruction and preventing mitochondrial damage in rabbit osteoarthritis (OA) model. However, whether LRWXG exerts its anti-OA activity through intrinsic bax-mitochondria cytochrome c-caspase signaling pathway in OA still requires further study. To address this problem, the OA model was induced by anterior cruciate ligament transection (ACLT) in rabbit and then treated with LRWXG. The results showed that LRWXG could inhibit the loss of collagen in cartilage matrix, protect trabecular bone in subchondral, decrease the apoptosis of chondrocytes, down-regulate the expressions of active caspase-9, active caspase-3 and bax, and up-regulate the expression of bcl-2. In addition, LRWXG could up-regulate the expression of cyt-c in mitochondria, while down-regulate the expression of cyt-c in cytoplasm. These findings show that LRWXG inhibits cartilage degradation via an intrinsic bax-mitochondria cytochrome c-caspase pathway in OA. [ABSTRACT FROM AUTHOR]

The polysaccharides used in the treatment of osteoarthritis (OA) mainly include sodium hyaluronate, chondroitin sulfate, chitosan, xanthan gum, Low molecular weight heparin, alginate and other polysaccharides. This review summarizes the recent advances in the chemistry and biological activities of polysaccharides for the treatment of OA. [ABSTRACT FROM AUTHOR]

We have previously reported the application of low molecular weight XG(LM-XG), with molecular weights ranging from 1 × 10 6 Da to 1.5 × 10 6 Da for treating osteoarthritis. In this study, we investigated the anti-apoptotic activity of LM-XG under oxidative stress conditions, activated by hydrogen peroxide (H 2 O 2 )-treated chondrocytes in vitro . Chondrocytes were pretreated with various doses of LM-XG (0, 10, 100, 500, or 1000 μg/mL) or 1000 μg/mL sodium hyaluronate for 12 h, and then exposed to 0.5 mmol/L H 2 O 2 for another 12 h. After treatment, chondrocyte viability was evaluated using a cell counting kit-8; DNA fragmentation was detected using Hoechst33258 staining; the percentage of DNA fragmentation was evaluated using the diphenylamine DNA assay kit; the apoptosis rate was evaluated using flow cytometry; chondrocyte ultra-microscopic morphology was observed using transmission electron microscopy; intracellular reactive oxygen species levels were observed and quantified using 2,7-dichlorofuorescin diacetate, mitochondrial permeability transition analysis was performed using MitoTracker Red CMXRos and 4′,6-diamidino-2-phenylindole staining; and finally, caspase-3 activity was detected by western blot. The results showed that, compared with H 2 O 2 -treated chondrocytes, LM-XG improved cell viability, decreased the percentage of DNA fragmentation, reduced the apoptosis rate, decreased the levels of intracellular reactive oxygen species and mitochondrial permeability transition, reverted the morphological damage, and downregulated cleaved caspase-3 levels. These results demonstrate that LM-XG has anti-apoptotic activity in H 2 O 2 -treated chondrocytes. [ABSTRACT FROM AUTHOR]

In this study, we evaluated the immunomodulatory effects of xanthan gum (XG) in RAW264.7 macrophages and the underlying molecular mechanisms. We used scanning electron microscopy (SEM) to analyze the morphology of XG-treated RAW264.7 cells with and without lipopolysaccharide (LPS) stimulation and investigated the subsequent effects on nitric oxide (NO), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor (TNF-α), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) levels in LPS-activated mouse RAW264.7 macrophages. We also analyzed the binding affinity of XG to Toll-like receptor 4 (TLR4) with surface plasmon resonance (SPR) analysis and observed that XG decreased NO, IL-6 and TNF-α secretion into the culture medium and iNOS and COX-2 protein levels induced by LPS. This study reveals a two-way immunomodulatory effect of XG on inflammatory mediators in RAW264.7 macrophages that may involve the TLR4 signal pathway, providing a pharmacological basis for the use of XG in the control of inflammatory disorders. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is one of the most common chronic diseases and characterized by degradation of articular cartilage. We have previously reported xanthan gum (XG) injection preparation with high molecular weights ( Mw ) in ranging from 3 × 10 6 Da to 5 × 10 6 Da (HM-XG) could enhance the viscosity of synovial fluid, protect joint cartilage in rabbit, and the therapeutical effect has no significance difference with an existing clinical medication (sodium hyaluronate, SH) at the same injection frequency (once weekly for 5 weeks). Herein, we prepared a XG injection preparation with a low M w (LM-XG) in ranging from 1 × 10 6 Da to 1.5 × 10 6 Da, and evaluated the therapeutical effect for OA therapy at once every 2 weeks for 5 weeks with an SH at once weekly for 5 weeks as reference. The model of OA was induced using anterior cruciate ligament transection (ACLT) in a rabbit in vivo and also using sodium nitroprusside (SNP) in cell culture in vitro . The results showed that LW-XG could also protect cartilage from damage, decrease the concentration of nitric oxide (NO) in synovial fluid and reverse the amplification of the knee joint width similar to HM-XG as our previously reported. At the cellular level, LW-XG promotes proliferation while decreases apoptosis of chondrocytes. Mechanistically at the molecular level, these effects are elicited via down-regulation of the protein levels of caspase-3 and bax and up-regulation of the protein levels of bcl-2 in cartilage in both in vivo and in vitro. These results showed that LW-XG maybe become an excellent candidate long-acting drug for treating OA. [ABSTRACT FROM AUTHOR]

A practical molecular weight determination model of xanthan gum (XG), based on near-infrared (NIR) spectroscopy, was built in this study. Two sample measurement modules, integrating sphere module and fiber-optic probe module, were compared, and the best partial least square (PLS) regression model was based on fiber-optic probe module. The values of coefficient of determination in calibration ( R 2 c ), coefficient of determination in prediction ( R 2 p ), residual predictive deviation (RPD) and root mean square error of prediction (RMSEP) were 0.967, 0.975, 6.028 and 0.250 × 10 6 Da, respectively. The molecular weight range, linearity, accuracy and precision of the established method were also validated. Furthermore, influence factors on this method were discussed in order to establish an appropriate measurement protocol. Results showed that the proposed NIR method may be suitable for practical applications in manufacturing plants and probably be accepted as a good alternative approach for fast determination of molecular weight of XG in production process. [ABSTRACT FROM AUTHOR]

Abstract: The objective of this study was to evaluate the alleviative effect of intra-articular (IA) injection of xanthan gum (XG) on pain and cartilage degradation in a model of monosodium iodoacetate (MIA)-induced knee osteoarthritis (OA). The rheological study and hyaluronidase (HAse) degradation analysis of XG injection were presented. The effect of pain relief was determined by measurements of paw withdrawal threshold and weight bearing by hind limbs. The protective effect on the cartilage was evaluated by gross morphological observation and histological evaluation of knee joints. The effect was investigated in two protocols: a therapeutic treatment protocol, and a prophylactic treatment protocol. Our results showed that HAse had no effect on the rheological properties of XG injection. Local XG administration in both protocols could reduce OA pain and alleviate the joint cartilage degradation induced by MIA. IA injection of XG might be an effective method for OA treatment in human. [Copyright &y& Elsevier]

Abstract: We have previously shown that intra-articular injection of xanthan gum (XG) could protect the joint cartilage and reduce osteoarthritis progression. In this study, we investigated the preliminary cytotoxicity of XG on chondrocytes, evaluated the effects of XG on the proliferation and the protein expression of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinase-1 (TIMP-1) in interleukin-1β (IL-1β)-induced rabbit chondrocytes. Primary rabbit chondrocytes were cultured. After treatment with various concentrations of XG with or without 10ng/mL IL-1β, the proliferation of chondrocytes was evaluated using the MTT assay and the expression levels of MMPs and TIMP-1 were evaluated using ELISA. The results showed that XG alone displayed no adverse effects on cell viability and reversed significantly IL-1β-reduced cell proliferation in a dose-dependent manner. Furthermore, XG showed a dose-dependent inhibition in the IL-1β-induced release of MMPs while increasing TIMP-1 expression. These results strongly suggest that XG affords protection on IL-1β induced rabbit chondrocytes. [Copyright &y& Elsevier]

Abstract: This study was conducted to evaluate the protective effect of intra-articular (IA) injection of xanthan gum (XG) on articular cartilage in the papain-induced osteoarthritis (OA) model. The purified XG and injection were prepared and their qualities were evaluated. The rabbit knee OA model was induced through IA injection of papain and the protective effect on articular cartilage was evaluated through recording the width of knee joint, performing the morphological observation and histological evaluation of articular cartilage and synovium, measuring the sulphated glycosaminoglycans (GAGs) in cartilage. Our results showed that XG injection was of high transparency, low protein and endotoxin-free. IA injection of XG could protect the joint cartilage and this was probably an effective therapeutic method of OA. [Copyright &y& Elsevier]