Icariin attenuates LPS-induced acute inflammatory responses: involvement of PI3K/Akt and NF-kappaB signaling pathway.
This study aimed to investigate the mechanism underlying the attenuation of LPS-induced lung inflammation by icariin in vivo and in vitro. The anti-inflammatory effects of icariin on LPS-induced acute inflammatory and the molecular mechanism were investigated. Pretreatment with icarrin (20mg/kg) could attenuate acute lung inflammation by inhibiting mRNA expressions of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), metalloproteinase cycloxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) in the lung of LPS-treated mice. In addition, icariin suppressed the secretion of TNF-alpha, prostaglandin E2 (PGE(2)) and nitric oxide (NO) as well as NF-kappaB p65 activation. Furthermore, decreased myeloperoxidase (MPO) activity was observed in the lung tissue and LPS-induced cytotoxicity in the RAW 264.7 macrophages cells was also markedly attenuated by icariin. Western blotting analysis and confocal microscopy showed that icariin pretreatment reduced the nucleus transportation and constant level of NF-kappaB p65 in the RAW 264.7 macrophage cells. However, the protective effects of icariin were reversed by a PI3K/Akt inhibitor (wortmannin). Our in vitro and in vivo results suggested that activation of the PI3K/Akt pathway and the inhibition of NF-kappaB were involved in the protective effects of icariin on LPS-induced acute inflammatory responses.
Lab of Lung, Inflammation and Cancers, Huashan Hospital, Fudan University, Shanghai, 200040, China.
Chang-Qing
CQ
Xu
Bao-Jun
BJ
Liu
Jin-Feng
JF
Wu
Yan-Chun
YC
Xu
Xiao-Hong
XH
Duan
Yu-Xue
YX
Cao
Jing-Cheng
JC
Dong
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
D005419:Flavonoids; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D009195:Peroxidase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C056599:icariin