Protective effect of Acanthopanax senticosus extract against endotoxic shock in mice.
OBJECTIVE
In this study, we evaluated protective effect of Acanthopanax senticosus extract (ASE) and a possible signaling pathway involved during endotoxic shock induced by intraperitoneal injection lipopolysaccharide (LPS) and D-galactosamine (D-GalN) in BALB/c mice.


METHODS
Mice were intraperitoneal administrated with ASE (100, 200 or 400mg/kg) prior to injection of 50 microg/kg LPS and 1g/kg D-GalN. The levels of tumor necrosis-alpha (TNF-alpha) and interleukin-10 (IL-10) in serum and liver. Nitric oxide (NO) production in serum and inducible nitric oxide synthase (iNOS) protein level were investigated. Nuclear factor-kappa B (NF-kappaB) activation in liver was determined. Furthermore, we evaluated the effect of ASE pretreatment on infiltration of inflammatory cells into the heart, liver and lung of mice.


RESULTS
Treatment of mice with ASE prior to LPS/D-GalN injection significantly improved the survival rate. ASE pretreatment inhibited the elevation of TNF-alpha in serum and liver. ASE also decreased iNOS level in liver and the overproduction of nitric oxide (NO) in serum. In addition, IL-10 levels in serum and liver were markedly enhanced. ASE pretreatment inhibited NF-kappaB activation in liver of mice. Moreover, infiltration of inflammatory cells into the heart, liver and lung of mice was also attenuated by ASE pretreatment.


CONCLUSIONS
These results suggested that ASE protected mice against LPS/D-GalN-induced endotoxic shock involving inhibition of NF-kappaB activation, which caused down-regulation of TNF-alpha and involved up-regulation of IL-10. Acanthopanax senticosus may thus prove beneficial in the prevention of endotoxic shock.
Lin
Qiu-Ye
QY
Department of Bioscience and Biotechnology, Dalian University of Technology, Ganjingzi District, Dalian, People's Republic of China.
Jin
Li-Ji
LJ
Cao
Zhen-Hui
ZH
Li
Hua-Qiang
HQ
Xu
Yong-Ping
YP
D000818:Animals; D004305:Dose-Response Relationship, Drug; D028001:Eleutherococcus; D005260:Female; D016753:Interleukin-10 / Q000032:analysis / Q000097:blood; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000097:blood; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use*; D012772:Shock, Septic / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000097:blood
D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide