Isofraxidin exhibited anti-inflammatory effects in vivo and inhibited TNF-α production in LPS-induced mouse peritoneal macrophages in vitro via the MAPK pathway.
Isofraxidin (IF) is a Coumarin compound that can be isolated from medicinal plants, such as Sarcandra glabra (Thunb.). Nakai is widely used in Asian countries for the treatment of anti-bacterial, anti-inflammatory and anti-tumour action. The present investigation was designed to evaluate the effect of IF on inflammation and nociception. In addition, we investigated a potential novel mechanism to explain the anti-inflammatory properties of IF. In vivo, xylene-induced mouse ear edema, carrageenan-induced rat paw edema, LPS-induced mouse endotoxic shock, acetic acid-induced mice writhing and formalin-induced mouse pain models were used to evaluate the anti-inflammatory activity of IF. In vitro, we examined the effects of IF inhibition on TNF-α production and the regulation of ERK1/2 and p38 phosphorylation activity in LPS-induced mouse peritoneal macrophages. Our results demonstrated that IF can significantly decrease xylene-induced ear edema, carrageenan-induced paw edema, acetic acid-induced writhing and formalin-induced pain. Moreover, IF greatly inhibited the production of TNF-α in the serum of LPS-stimulated mice and peritoneal macrophages, and it decreased phospho-p38 and ERK1/2 protein expression in LPS-stimulated mouse peritoneal macrophages. Overall, our data suggest that IF possesses significant analgesic and anti-inflammatory activities that may be mediated through the regulation of pro-inflammatory cytokines, TNF-α and the phosphorylation of p38 and ERK1/2.
School of Medicine, Xi'an Jiaotong University, Xi'an 710061, P.R. China.
Xiaofeng
X
Niu
Wei
W
Xing
Weifeng
W
Li
Ting
T
Fan
Hua
H
Hu
Yongmei
Y
Li
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D002351:Carrageenan / Q000008:administration & dosage; D002478:Cells, Cultured; D003374:Coumarins / Q000008:administration & dosage*; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D005557:Formaldehyde / Q000008:administration & dosage; D008070:Lipopolysaccharides / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014992:Xylenes / Q000008:administration & dosage; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003374:Coumarins; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D014992:Xylenes; D005557:Formaldehyde; C008182:isofraxidin; D002351:Carrageenan; D048051:p38 Mitogen-Activated Protein Kinases