Ethanol extract from Artemisia vestita, a traditional Tibetan medicine, exerts anti-sepsis action through down-regulating the MAPK and NF-kappaB pathways.
Artemisia vestita Wall., a traditional Tibetan medicine, has wide clinical application for inflammatory diseases. However, its molecular mechanism of anti-inflammatory effect is poorly understood. In the present study, we investigated the anti-inflammatory activity and underlying mechanism of the ethanol extract from Artemisia vestita (AV-ext) on lipopolysaccharide (LPS)-induced sepsis. Pretreatment with AV-ext significantly decreased the levels of tumor necrosis factor-alpha (TNF-alpha) in serum and liver and lung tissues, and improved the survival of mice with experimental sepsis. AV-ext also remarkably reduced the expression levels of TNF-alpha, interleukin-1beta and cyclooxygenase-2 in LPS-stimulated RAW 264.7 macrophages and dose dependently suppressed the activation of mitogen-activated protein kinases (MAPKs), such as p38, extracellular signal-regulated kinase (ERK1/2) and c-Jun NH2-terminal kinase (JNK). Furthermore, pretreatment with AV-ext dose dependently inhibited the activation of nuclear factor-kappaB (NF-kappaB), as well as the degradation and phosphorylation of inhibitory kappaB (IkappaB) in LPS-activated RAW 264.7 macrophages. These results collectively reveal that AV-ext inhibits TNF-alpha release from macrophages by suppressing MAPK and NF-kappaB signaling pathways and suggest that AV-ext may be beneficial for the treatment of endotoxin shock or sepsis.
Sun
Yang
Y
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, PR China.
Li
Yi-Hua
YH
Wu
Xing-Xin
XX
Zheng
Wei
W
Guo
Zong-Hui
ZH
Li
Yang
Y
Chen
Ting
T
Hua
Zi-Chun
ZC
Xu
Qiang
Q
D000818:Animals; D019306:Artemisia / Q000737:chemistry*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D000431:Ethanol / Q000737:chemistry; D015870:Gene Expression / Q000187:drug effects; D020672:I-kappa B Proteins / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D038861:Medicine, Tibetan Traditional; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D018805:Sepsis / Q000378:metabolism / Q000401:mortality / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects; D013047:Specific Pathogen-Free Organisms; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D020672:I-kappa B Proteins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D000431:Ethanol; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases