NCPP treatment alleviates ConA-induced hepatitis via reducing CD4+T activation and NO production.
ABSTRACT Corynebacterium parvum (CP), a kind of immunomodulator, has been well documented in many diseases. Non-cell C. parvum product (NCPP) is a newly-found nano-preparation. To investigate the effect of NCPP on Con A-induced murine severe hepatitis, we pretreated mice with NCPP intraperitoneally. After 12 h , ConA (25 μg/g body wt) was injected intravenously to provoke severe hepatitis and the degree of liver injury was evaluated by serum transaminase analysis and heptatic tissue pathology. Results have shown that levels of serum transaminase and degree of liver injury in ConA/NCPP groups had significantly declined than those in ConA/PBS groups. Notably, results of flow cytometry have demonstrated that activation of CD4+T cells in ConA/NCPP groups has been down-regulated, compared with ConA/PBS groups. Further, levels of serum and KC-related nitric oxide (NO) was displayed significantly lower in ConA/NCPP groups than those in ConA/PBS groups. The results indicate that NCPP may alleviate ConA-induced hepatitis by reducing CD4+T activation and NO production.
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ABSTRACT: Paeoniflorin (PF) is one of the main effective components of the total glucosides of peony, which has been reported to have anti-inflammatory ability. However, the effects of paeoniflorin on concanavalin A (Con A)-induced hepatitis have not been carefully examined. The aim of this study was to investigate the protective effect of paeoniflorin and elucidate potential mechanisms of paeoniflorin on Con A-induced hepatitis. C57BL/6 mice were divided randomly into the following four experimental groups: PBS group, PF group, Con A group, and Con A+PF group. Mice received paeoniflorin (50mg/kg) by tail vein before Con A intravenous administration. We found that paeoniflorin pretreatment can significantly reduce the elevated plasma aminotransferase levels and liver necrosis in Con A-induced hepatitis. Also, paeoniflorin pretreatment suppressed the secretion of proinflammatory cytokines (TNF-α, INF-γ, IL-6), compared with Con A group. Meanwhile, paeoniflorin pretreatment decreased CD4(+), CD8(+) and NKT cell infiltration in the liver. Besides, we observed that paeoniflorin pretreatment can decrease the expression level of Toll-like receptor (TLR) 4 mRNA or protein in liver tissues. Further results showed that paeoniflorin pretreatment was capable of suppressing the activation of the NF-κB pathway by inhibiting IκBα kinase and p65 phosphorylation in Con A-induced liver injury. These results suggest that paeoniflorin pretreatment protects mice against Con A-induced liver injury via inhibition of several inflammatory mediators and, at least in part, by suppressing CD4(+), CD8(+) and NKT cell infiltration in liver. The beneficial effect of paeoniflorin may be related to the downregulation of TLR4 expression and the inhibition of NF-κB activation. Copyright © 2014. Published by Elsevier B.V.International Immunopharmacology 11/2014; 24(1):42-49. DOI:10.1016/j.intimp.2014.11.006 · 2.71 Impact Factor