Anti-inflammatory effect of 2-methoxy-4-vinylphenol via the suppression of NF-κB and MAPK activation, and acetylation of histone H3.
Although inflammation acts as host defense mechanism against infection or injury and is primarily a self limiting process, inadequate resolution of inflammatory responses leads to various chronic disorders. This work aimed to elucidate the anti-inflammatory effects of 2-methoxy-4-vinylphenol (2M4VP) isolated from pine needles in LPS-stimulated RAW264.7 cells. Some key pro-inflammatory mediators including nitric oxide (NO), prostaglandins (PGE(2)), inducible NO synthase (iNOS), and cyclooxygenase-2 (COX-2) were studied by sandwich ELISA and western blot. In addition, suppression of NF-κB and MAPK activation, and histone acetylation was studied by western blot analysis and immunostaining. 2M4VP dosedependently inhibited NO and PGE(2) production and also blocked LPS-induced iNOS and COX-2 expression. In addition, 2M4VP potently inhibited the translocation of NF-κB p65 into the nucleus by IκB degradation following IκB-α phosphorylation and the phosphorylation of MAPKs such as p38, ERK1/2, and JNK. Also, 2M4VP inhibited hyper-acetylation of histone H3 (Lys9/Lys14) induced by LPS. Taken together, our results suggest that 2M4VP, a naturally occurring phenolic compound, exert potent anti-inflammatory effects by inhibiting LPS-induced NO, PGE(2), iNOS, and COX-2 in RAW264.7 cells. These effects are mediated by suppression of NF-κB and MAPK activation and histone acetylation.
Medicinal Plant Resources Major, Andong National University, Andong, 760749, Korea. jjb8376@gmail.com
Jin Boo
JB
Jeong
Se Chul
SC
Hong
Hyung Jin
HJ
Jeong
Jin Suk
JS
Koo
D000107:Acetylation; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D006139:Guaiacol / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D006657:Histones / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D028223:Pinus / Q000737:chemistry; D010936:Plant Extracts / Q000494:pharmacology*; D014753:Vinyl Compounds / Q000302:isolation & purification / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006657:Histones; D016328:NF-kappa B; D010936:Plant Extracts; D014753:Vinyl Compounds; D006139:Guaiacol; C526552:2-methoxy-4-vinylphenol; D020928:Mitogen-Activated Protein Kinases