Icariin derivative inhibits inflammation through suppression of p38 mitogen-activated protein kinase and nuclear factor-kappaB pathways.
In this study we investigated the anti-inflammatory effects of an icariin derivative (3,5-dihydroxy-4'-methoxy-6'',6''-dimethy1-4'',5''-dihydropyrano[2'',3'':7,8]-flavone). We found that this icariin derivative inhibits tumor necrosis factor-alpha (TNF-alpha) production, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA expression, and protein expression in lipopolysaccharide (LPS) stimulated RAW264.7 macrophages. It also alleviates paw edema induced by carrageenan in mice. To clarify the molecular mechanisms underlying these anti-inflammatory effects, we examined the effects of this compound on the phosphorylation of mitogen-activated protein kinase (MAPK), phosphorylation of inhibitory kappaBalpha (IkappaBalpha), and nuclear translocation of p65 subunit of nuclear factor (NF)-kappaB, and found it suppresses the activation of p38 MAPK and inhibits translocation of NF-kappaB p65 to the nucleus through decreasing the phosphorylation of IkappaBalpha. As a result of these properties, this icariin derivative can be considered as a potential drug for inflammatory diseases.
Chen
Shao-Rui
SR
Laboratory of Pharmacology and Toxicology, Sun Yat-Sen University, Guangzhou, China.
Xu
Xiang-Zhen
XZ
Wang
Yu-Hua
YH
Chen
Jian-Wen
JW
Xu
Suo-Wen
SW
Gu
Lian-Quan
LQ
Liu
Pei-Qing
PQ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D015153:Blotting, Western; D018929:Cell Culture Techniques; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D047309:Flavones / Q000737:chemistry / Q000494:pharmacology*; D005419:Flavonoids / Q000737:chemistry*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D021381:Protein Transport; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051996:Transcription Factor RelA / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
C554101:3,5-dihydroxy-4'-methoxy-6',6'-dimethyl-4',5'-dihydropyrano(2',3'-7,8)flavone; D000894:Anti-Inflammatory Agents, Non-Steroidal; D047309:Flavones; D005419:Flavonoids; D008070:Lipopolysaccharides; D016328:NF-kappa B; D051996:Transcription Factor RelA; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D048051:p38 Mitogen-Activated Protein Kinases; C056599:icariin