Paeoniflorin protects against concanavalin A-induced hepatitis in mice

• It is firstly reported that paeoniflorin provides a protective effect on Con A-induced hepatitis in mice.
• Paeoniflorin pretreatment protects mice against Con A-induced hepatitis via inhibition of several inflammatory mediators and, at least in part, by suppressing CD4+, CD8+ and NKT cells infiltration in liver.
• The NF-κB and TLR4 signaling pathways may be involved in the protective effects of paeoniflorin.

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 (50 mg/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.