Morin modulates the oxidative stress-induced NF-kappaB pathway through its anti-oxidant activity.
Morin is a flavone that has anti-inflammatory effects through a mechanism that is not well understood. Based on the extreme sensitive nature of the transcription factor, NF-kB to redox change, it is postulated that morin's anti-NF-kappaB activation likely depends on its ability to scavenge excessive reactive species [RS]. The present study assessed the extent of morin's ability to modulate RS-induced NF-kappaB activation through its scavenging activity. Results indicate that morin neutralized RS in vitro and inhibited t-BHP-induced RS generation. It also examined morin for suppressed redox-sensitive transcription factor NF-kappaB activation via reduced DNA binding activity, I kappaB alpha phosphorylation and p65/p50 nuclear translocation. The more important finding was that suppression of the NF-kappaB cascade by morin was modulated through the ERK and p38 MAPKs signal transduction pathways in endothelial cells. As a consequence, morin's anti-oxidant effect extended expression level of NF-kappaB dependent pro-inflammatory genes, thereby reducing COX-2, iNOS and 5-LOX. The data indicate that morin has strong anti-oxidative power against RS-induced NF-kappaB modulation through the ERK and p38 MAPKs signalling pathways by its RS scavenging activity. The significance of the current study is the new revelation that morin may have potential as an effective anti-inflammatory therapeutic agent.
Kim
Ji Min
JM
Department of Pharmacy and Molecular Inflammation Research Center for Aging (MRCA) Intervention, Pusan National University, Busan, Korea.
Lee
Eun Kyeong
EK
Park
Gwangli
G
Kim
Mi Kyung
MK
Yokozawa
Takako
T
Yu
Byung Pal
BP
Chung
Hae Young
HY
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D001665:Binding Sites; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D051550:I-kappa B Kinase; D018836:Inflammation Mediators / Q000378:metabolism; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D051996:Transcription Factor RelA / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D020122:tert-Butylhydroperoxide / Q000494:pharmacology; D047309:Flavones
D000893:Anti-Inflammatory Agents; D001094:Arachidonate 5-Lipoxygenase; D051546:Cyclooxygenase 2; D004247:DNA; D048049:Extracellular Signal-Regulated MAP Kinases; D005419:Flavonoids; D016166:Free Radical Scavengers; D051550:I-kappa B Kinase; D018836:Inflammation Mediators; D008981:Molsidomine; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D052247:Nitric Oxide Synthase Type II; D051996:Transcription Factor RelA; D048051:p38 Mitogen-Activated Protein Kinases; D020122:tert-Butylhydroperoxide; C498145:Rela protein, rat; C002385:linsidomine; C008548:morin; D047309:Flavones; C496318:Nos2 protein, rat; C489691:Ptgs2 protein, rat