Methylalpinumisoflavone inhibits lipopolysaccharide-induced inflammation in microglial cells by the NF-kappaB and MAPK signaling pathway.
Neuroinflammation is chronic inflammation within the brain that is attributed to prolonged activation of microglial cells and results in neurodegenerative events, such as neuronal dysfunction and neuronal loss. Therefore, suppression of neuroinflammation would theoretically slow progression of neurodegenerative disease. In this study, we investigated the anti-inflammatory effects of 4'-O-methylalpinumisoflavone (methylalpinumisoflavone), isolated from Cudrania tricuspidata, against LPS-induced microglial activation in BV2 cells. Exposure of BV2 cells to LPS (0.5 µg/mL) significantly increased production of pro-inflammatory mediators, including NO, PGE(2), and pro-inflammatory cytokines. Conversely, pre-treatment with methylalpinumisoflavone (10 and 20 µg/mL) prior to treatment with LPS resulted in a significant decrease of LPS-induced production of pro-inflammatory mediators in a dose-dependent manner. In addition, reduction of pro-inflammatory mediators by treatment with methylalpinumisoflavone prior to treatment with LPS was accompanied by a decrease in translocation of NF-κB p50 and p65 from the cytoplasm to the nucleus and by a decrease in activation of mitogen-activated protein kinases (MAPKs), such as ERK1/2 and JNK. Taken together, these results suggest that methylalpinumisoflavone suppressed LPS-induced microglial activation and production of pro-inflammatory mediators by decreasing NF-κB signaling and by phosphorylation of MAPKs. These results suggest the potential of methylalpinumisoflavone as an anti-inflammatory drug candidate.
Environmental Toxico-Genomic and Proteomic Center, College of Medicine, Korea University, Seoul 136-701, Korea.
Ji-Youn
JY
Lim
Bang Yeon
BY
Hwang
Kwang-Woo
KW
Hwang
So-Young
SY
Park
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism*; D007529:Isoflavones / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism
C507553:4'-O-methylalpinumisoflavone; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D007529:Isoflavones; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases; D015232:Dinoprostone