The neoflavonoid latifolin isolated from MeOH extract of Dalbergia odorifera attenuates inflammatory responses by inhibiting NF-κB activation via Nrf2-mediated heme oxygenase-1 expression.
In Korea and China, the heartwood of Dalbergia odorifera T. Chen is an important traditional medicine used to treat blood disorders, ischemia, swelling, and epigastric pain. In this study, we investigated the inhibitory effects of latifolin, a major neoflavonoid component isolated from the MeOH extract of D. odorifera, on the inflammatory reaction of thioglycollate-elicited peritoneal macrophages exposed to lipopolysaccharide, with a particular focus on heme oxygenase-1 (HO-1) expression and nuclear factor-κB (NF-κB) signaling. Latifolin significantly inhibited the protein and mRNA expression of inducible nitric oxide synthase and COX-2, reduced NO, prostaglandins E2, tumor necrosis factor-α, and interleukin-1β production in primary murine peritoneal macrophages exposed to lipopolysaccharide. Latifolin also suppressed inhibitor κB-α levels, NF-κB nuclear translocation, and NF-κB DNA-binding activity. Furthermore, latifolin upregulated HO-1 expression via nuclear transcription factor-E2-related factor 2 (Nrf2) nuclear translocation. In addition, using inhibitor tin protoporphyrin IX (SnPP), an inhibitor of HO-1, it was verified that the inhibitory effects of latifolin on the proinflammatory mediators and NF-κB DNA-binding activity were associated with the HO-1 expression. These results suggested that the latifolin-mediated up-regulation of HO-1 expression played a critical role in anti-inflammatory effects in macrophages. This study therefore identified potent therapeutic effects of latifolin, which warrants further investigation as a potential treatment for inflammatory diseases.
Hanbang Body Fluid Research Center, Wonkwang University, Iksan, 570-749, Korea.
Dong-Sung
DS
Lee
Kyoung-Su
KS
Kim
Wonmin
W
Ko
Bin
B
Li
Samell
S
Keo
Gil-Saeng
GS
Jeong
Hyuncheol
H
Oh
Youn-Chul
YC
Kim
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D035782:Dalbergia / Q000737:chemistry*; D015232:Dinoprostone / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D020672:I-kappa B Proteins / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010636:Phenols / Q000302:isolation & purification / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D020672:I-kappa B Proteins; D053583:Interleukin-1beta; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495636:Nfe2l2 protein, mouse; C000606205:Nfkbia protein, mouse; D010636:Phenols; D014409:Tumor Necrosis Factor-alpha; C543734:latifolin; D000072000:NF-KappaB Inhibitor alpha; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D015232:Dinoprostone
Dalbergia odorifera; heme oxygenase-1; inflammation; latifolin; macrophages; nuclear factor-κB