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Abstract: In this study, an oxidative stress model was first developed in a mouse macrophage cell line (RAW264.7 cells) by infecting the cells with porcine circovirus type 2 (PCV2). The regulatory effect of Sophora subprosrate polysaccharide (SSP) on PCV2-induced oxidative stress was investigated. The results showed that after infection with PCV2, reactive oxygen species (ROS) and nitric oxide (NO) production, myeloperoxidase (MPO) activity, and inducible nitric oxide synthase (iNOS) expression were significantly increased. Meanwhile, the ratio of reduced glutathione to oxidized glutathione (GSH/GSSG) and hydroxyl radical prevention capacity were greatly reduced. These data indicate successful creation of an oxidative stress model in RAW264.7 cells. A dramatic decrease in cell viability was observed in the cells exposed to oxidative stress compared to the control. When the cells were treated with SSP in concentrations of 100, 200 or 400μg/mL post PCV2 infection, an increase in the GSH/GSSG ratio and hydroxyl radical prevention capacity was observed. We also observed decreased ROS and NO production, MPO activity, and iNOS expression in the infected cells. Our results demonstrated that PCV2 infection was able to induce oxidative stress in RAW264.7 cells and that SSP could reduce the negative effects resulting from the PCV2 infection. [Copyright &y& Elsevier]

Abstract: The objective of the current study is to investigate the protective effect of carboxymethylpachymaran (CMP) on the immune system of mice via multiple infections with porcine circovirus type 2 (PCV2). The in vivo results showed that CMP administration significantly improved the spleen or thymus index, promoted the proliferation activities of T or B lymphocytes, and increased the production of glutathione, the superoxidase dismutase capacity, and the total antioxidant capacity in the spleen or thymus of PCV2-infected mice. The administration of different CMP doses to PVC2-inoculated mice resulted in the upregulation of IL-2 and IFN-α or the downregulation of IL-10 levels in the serum. These findings suggest that CMP has potential applications in regulating immunological functions to overcome the immunosuppresion caused by PCV2 infection in mice. The findings may also prove useful in designing effective therapies against PCV2 infection. [Copyright &y& Elsevier]

The purpose of this study was to investigate the regulation of Sophora subprosrate polysaccharide (SSP) on inflammatory response and histone acetylation modification of RAW264.7 cells (mouse mononuclear macrophage cell line) infected with porcine circovirus type 2 (PCV2). We further explored the role of inflammatory response and histone acetylation modification on the basis of the original study. The results showed that SSP decreased the secretion levels of TNF-α and IL-6 and the intracellular iNOS, COX-2 enzyme activities and their mRNA expression levels in PCV2 infected RAW264.7 cells, but increased the level of IL-10 secretion and its mRNA expression. SSP inhibited the phosphorylation levels of proteins of p65, ERK1/2, p38 and c-Jun in RAW264.7 cells infected with PCV2. The activities of HAT and HDAC enzymes and the mRNA expression levels of HAT1 and HDAC1 were increased when the PCV2-infected RAW264.7 cells were treated by SSP. Meanwhile, the expression of acetylation modification of histones both H3 and H4 was obviously inhibited. In conclusion, SSP may reduce the acetylation levels of both H3 and H4 and activate NF-κB/MAPKs/c-Jun signaling pathway by increasing the activity of HADC enzyme and the expression of HDAC mRNA, further inhibiting inflammatory response by regulating the gene expression levels of inflammatory factors. The findings indicated that the molecular mechanism of how traditional Chinese medicine polysaccharide regulates inflammatory signal pathways and inflammatory factors by regulating histone acetylation. [ABSTRACT FROM AUTHOR]

In the present study, effect of Sophora subprosrate polysaccharide on PCV2 infection-induced inflammation and histone acetylation modification in swine alveolar macrophage 3D4/2 cells was described for the first time. The relationship between histone acetylation modifications and inflammation response was investigated. The results showed that PCV2 infection induced inflammation by promoting the secretion of TNF-α, IL-1β, IL-6 and IL-10 in 3D4/2 cells. The production of TNF-α, IL-1β and IL-6 and their mRNA expression levels markedly decreased while the level and mRNA expression of IL-10 were elevated when the cells were treated with Sophora subprosrate polysaccharide. The SSP also decreased the activity of HATs, histone H3 acetylation (Ac-H3) and histone H4 acetylation (Ac-H4), p65 phosphorylation (P-p65) in the cells infected with PCV2 while HDACs activity was down-regulated, which involved in the inhibitory effect of SSP on histone acetylation and NF-κB signaling pathways activation. Down-regulation of HAT1 mRNA expression and up-regulation of HDAC1 mRNA expression further support the inhibitory effect of SSP on histone acetylation. In conclusion, Sophora subprosrate polysaccharide antagonized inflammatory responses induced by PCV2, via mechanisms involved in histone acetylation and NF-κB signaling pathways. [ABSTRACT FROM AUTHOR]

In the present study, the inhibitory effect of Sophora subprosrate polysaccharide (SSP) on PCV-2-induced mitochondrial respiratory burst in RAW264.7 cells was first investigated. The findings suggested that SOD activity and the anti-superoxide anion radical activity of the RAW264.7 cells were significantly decreased after PCV-2 infection, and MnSOD mRNA levels were significantly decreased, while NOX2 mRNA levels and protein expression were increased. Meanwhile, the O 2 •− levels and mitochondrial membrane potentials were significantly increased. After treatment with SSP, significant increases in the activities of SOD, anti-superoxide anion radical activities, and MnSOD mRNA levels in the PCV-2 infected cells were observed. Meanwhile, significant increases in NOX2 mRNA levels and protein expression, O 2 •− levels and mitochondrial membrane potentials were also observed. The results showed that PCV2 infection resulted in the mitochondria oxidative stress of RAW264.7 cells as indicated by an increasing mitochondrial membrane potential, which was then inhibited by SSP. It was concluded that RAW264.7 cells treated with SSP could suffer from mitochondrial damage, which may be mediated by the inhibition of the mitochondrial membrane potential. [ABSTRACT FROM AUTHOR]

Abstract: The aim of the present study was to investigate the immunomodulatory effect and antioxidant activity of carboxymethylpachymaran on cyclophosphamide-induced immunosuppression in mice in vivo. The results showed that carboxymethylpachymaran could be used to overcome the cyclophosphamide-induced immunosuppression in mice. Moreover, it significantly increased the thymus and spleen indices, lysozyme, catalase and superoxidase dismutase activities, and total antioxidant capacity. In contrast, it decreased xanthine oxidase activity and malondialdehyde levels. The results indicated that carboxymethylpachymaran might play an important role in the prevention of oxidative damage in the immunological system. [Copyright &y& Elsevier]

Abstract: Potentilla anserine polysaccharide (PAP) was studied in vivo to investigate its antioxidant activity using the model of dexamethasone-induced oxidative stress in mice. The investigation demonstrated that PAP at 50, 100 or 200mg/kg body weight for 7 days respectively increased thymus index and spleen index, glutathione level, superoxidase dismutase activity and total antioxidant capacity in both thymus and spleen and decreased the content of H2O2 in spleen and NOthymus and spleen of mice. The results revealed that PAP was able to overcome dexamethasone-induced oxidative stress and might play an important role in repairs of oxidative damage in immunological system. [Copyright &y& Elsevier]