Neoflavonoid Latifolin Isolated from MeOH Extract of Dalbergia odorifera Attenuates Inflammatory Responses by Inhibiting NF‐κB Activation via Nrf2‐Mediated Heme Oxygenase‐1 Expression

• Published in: Phytotherapy research Vol. 28; no. 8; pp. 1216 - 1223
• Main Authors: Lee, Dong‐Sung, Kim, Kyoung‐Su, Ko, Wonmin, Li, Bin, Keo, Samell, Jeong, Gil‐Saeng, Oh, Hyuncheol, Kim, Youn‐Chul
• Format: Journal Article
• Language: English
• Published: England J. Wiley 01-08-2014; Blackwell Publishing Ltd
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Cells, Cultured; Cyclooxygenase 2 - metabolism; Dalbergia; Dalbergia - chemistry; Dalbergia odorifera; Dinoprostone - metabolism; gene expression; gene expression regulation; heartwood; hematologic diseases; heme; heme oxygenase-1; Heme Oxygenase-1 - metabolism; I-kappa B Proteins - metabolism; inducible nitric oxide synthase; inflammation; Inflammation - metabolism; interleukin-1beta; Interleukin-1beta - metabolism; ischemia; latifolin; lipopolysaccharides; macrophages; Macrophages, Peritoneal - drug effects; Membrane Proteins - metabolism; messenger RNA; Mice; Mice, Inbred C57BL; necrosis; NF-E2-Related Factor 2 - metabolism; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; NF-KappaB Inhibitor alpha; nitric oxide; Nitric Oxide Synthase Type II - metabolism; nuclear factor-κB; pain; Phenols - isolation & purification; Phenols - pharmacology; primary productivity; prostaglandins; protoporphyrin; Signal Transduction - drug effects; therapeutics; tin; traditional medicine; transcription factor NF-kappa B; tumor necrosis factor-alpha; Tumor Necrosis Factor-alpha - metabolism; China; Korean Peninsula; nuclear factor-κB; macrophages; Dalbergia odorifera; heme oxygenase-1; inflammation; latifolin
• ISSN: 0951-418X; 1099-1573
• DOI: 10.1002/ptr.5119

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. Copyright © 2014 John Wiley & Sons, Ltd.