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Paeoniflorin Inhibits Systemic Inflammation and Improves Survival in Experimental Sepsis
Author(s) -
Jiang WangLin,
Chen XiGuang,
Zhu HaiBo,
Gao YuBai,
Tian JingWei,
Fu FengHua
Publication year - 2009
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2009.00415.x
Subject(s) - paeoniflorin , lipopolysaccharide , sepsis , pharmacology , myeloperoxidase , inflammation , medicine , intraperitoneal injection , systemic inflammation , chemistry , immunology , chromatography , high performance liquid chromatography
The present study was carried out to investigate the effects of paeoniflorin in cultured RAW264.7 cell line as well as in an experimental model of sepsis induced by cecal ligation and puncture, and intraperitoneal injection (i.p.) of lipopolysaccharide in rats. Results showed that paeoniflorin concentration‐dependently down‐regulated the levels of TNF‐α, IL‐6 and high‐mobility group‐box 1 protein in lipopolysaccharide‐induced RAW264.7 cell, inhibited the IκB kinase pathway and modulated NF‐κB. Intravenous injection (i.v.) of paeoniflorin alone or in combination with imipenem reduced i.p. of lipopolysaccharide or cecal ligation and puncture‐induced lethality in rats. In addition, serum levels of TNF‐α, IL‐6, high‐mobility group‐box 1 protein, triggering receptor expressed on myeloid cells and endotoxin were down‐regulated; by contrast, serum levels of IL‐10 were up‐regulated. Amelioration of hemodynamics, decrease of enzyme levels, decrease of myeloperoxidase in lung, liver, and small intestine were also found after paeoniflorin injection. These data indicate that the anti‐sepsis effect of paeoniflorin was mediated by decreasing local and systemic levels of a wide spectrum of inflammatory mediators. This work provides the first evidence that paeoniflorin has the capacity to inactivate inflammatory response in sepsis and the anti‐inflammatory mechanism of paeoniflorin may inhibit activation of the NF‐κB pathway by inhibiting IκB kinase activity.