δ-Amyrone inhibits lipopolysaccharide-induced inflammatory cytokines and protects against endotoxic shock in mice.
δ-Amyrone (13(18)-Oleanen-3-one), which is an active constituent extracted and separated from Sedum lineare Thunb., has been found to possess a potent anti-inflammatory effect in different inflammation model animals. But its effects on lipopolysaccharide (LPS)-induced endotoxic shock have not been previous explored. The aim of this study is to evaluate the effect of δ-Amyrone on LPS-induced inflammatory cytokines and the protective effect on endotoxic shock mice. Experimental animals received δ-amyrone (4 and 8 mg/kg, i.p.) and dexamethasone (DEX) (5 mg/kg, i.p.) at 24 and 1 h before LPS injection. δ-Amyrone treatment significantly decreased mortality rate, tissues myeloperoxodase (MPO) activity, p65 NF-κB protein expression when compared with the LPS groups. The levels of tumor nectosis factor-alphagene (TNF-α) and interleukin-6 (IL-6) both in serum and lung, liver, kidney tissues, as well as the accumulation of nitric oxide (NO) in serum were decreased by δ-amyrone in response to p65 nuclear factors-kappa B (NF-κB). These results suggest that the protective activity of δ-amyrone on LPS-induced endotoxic shock is attributed to reducing NO production and mediating the pro-inflammatory cytokines, inhibited NF-κB expression.
School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, PR China. Electronic address: niuxf@mail.xjtu.edu.cn.
Xiaofeng
X
Niu
School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, PR China.
Huan
H
Yao
School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, PR China. Electronic address: liwf@mail.xjtu.edu.cn.
Weifeng
W
Li
School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, PR China.
Qingli
Q
Mu
School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, PR China.
Huani
H
Li
School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, PR China.
Yu
Y
Wang
School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, PR China.
Hailin
H
Zhang
D000818:Animals; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced*; D015850:Interleukin-6 / Q000097:blood; D007668:Kidney / Q000201:enzymology; D008070:Lipopolysaccharides; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000097:blood; D009195:Peroxidase / Q000737:chemistry; D020011:Protective Agents / Q000494:pharmacology*; D012772:Shock, Septic / Q000517:prevention & control*; D014315:Triterpenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D020011:Protective Agents; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; C511312:amyrone; D009195:Peroxidase
Endotoxic shock; Inflammatory cytokines; Lipopolysaccharide; NF-κB; δ-Amyrone