Paeoniflorin inhibits systemic inflammation and improves survival in experimental sepsis.
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-alpha, IL-6 and high-mobility group-box 1 protein in lipopolysaccharide-induced RAW264.7 cell, inhibited the IkappaB kinase pathway and modulated NF-kappaB. 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-alpha, 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-kappaB pathway by inhibiting IkappaB kinase activity.
Jiang
Wang-Lin
WL
College of Marine Life Science, Ocean University of China, Qingdao, China.
Chen
Xi-Guang
XG
Zhu
Hai-Bo
HB
Gao
Yu-Bai
YB
Tian
Jing-Wei
JW
Fu
Feng-Hua
FH
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D001806:Blood Urea Nitrogen; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D002432:Cecum / Q000293:injuries / Q000601:surgery; D002460:Cell Line; D004796:Clinical Enzyme Tests; D004268:DNA-Binding Proteins / Q000032:analysis; D004731:Endotoxins / Q000097:blood / Q000633:toxicity; D005960:Glucosides / Q000494:pharmacology*; D006439:Hemodynamics / Q000502:physiology; D015378:Imipenem / Q000494:pharmacology; D007249:Inflammation / Q000473:pathology*; D018836:Inflammation Mediators / Q000097:blood / Q000502:physiology; D007421:Intestine, Small / Q000187:drug effects / Q000201:enzymology; D019344:Lactic Acid / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D008264:Macrophages / Q000737:chemistry / Q000187:drug effects; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D051379:Mice; D039821:Monoterpenes; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011971:Receptors, Immunologic / Q000097:blood; D012772:Shock, Septic / Q000139:chemically induced / Q000401:mortality*; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D006027:Glycosides
D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001565:Benzoates; D001952:Bridged-Ring Compounds; D004268:DNA-Binding Proteins; D004731:Endotoxins; D005960:Glucosides; D015378:Imipenem; D018836:Inflammation Mediators; D019344:Lactic Acid; D008562:Membrane Glycoproteins; D039821:Monoterpenes; D009195:Peroxidase; D011971:Receptors, Immunologic; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; C408842:TREM1 protein, human; C015423:peoniflorin; D006027:Glycosides