title: A Dalbergia odorifera extract improves the survival of endotoxemia model mice by inhibiting HMGB1 release.
abstract: BACKGROUND
  Dalbergia odorifera T. Chen (Leguminosae) is an indigenous medicinal herb that is widely used as a popular remedy in northern and eastern Asia. However, the cellular mechanisms underlying the biological activity of D. odorifera are not fully elucidated.
  
  
  METHODS
  Anti-inflammatory effect of D. odorifera extract (DOE) was determined through intraperitoneal injection in a mouse model of endotoxemia induced by lipopolysaccharide (LPS). RAW 264.7 cells, a murine macrophage, were also treated with LPS to generate a cellular model of inflammation, and investigated the anti-inflammatory activity and underlying mechanisms of DOE and its constituent isoliquiritigenin.
  
  
  RESULTS
  DOE dose-dependently inhibited LPS-induced release of high mobility group box 1 (HMGB1), a late proinflammatory cytokine, and decreased cytosolic translocation of HMGB1 in RAW264.7 cells. This inhibitory effect of DOE on HMGB1 release was observed in cells treated with DOE before or after LPS treatment, suggesting that DOE is effective for both treatment and prevention. In addition, DOE significantly inhibited LPS-induced formation of nitric oxide (NO) and expression of inducible NO synthase (iNOS) in a dose-dependent manner. These effects of DOE were accompanied by suppression of HMGB1 release triggered by LPS, suggesting a possible mechanism by which DOE modulates HMGB1 release through NO signaling. Isoriquiritigenin, a constituent of DOE, also attenuated LPS-triggered NO formation and HMGB1 release in RAW264.7 cells, indicating that isoriquiritigenin is an indexing molecule for the anti-inflammatory properties of DOE. Furthermore, c-Jun N-terminal kinase, but not extracellular signal-regulated kinase and p38, mediated DOE-dependent inhibition of HMGB1 release and NO/iNOS induction in RAW 264.7 cells exposed to LPS. Notably, administration of DOE ameliorated survival rates in a mouse model of endotoxemia induced by LPS, where decreased level of circulating HMGB1 was observed.
  
  
  CONCLUSIONS
  These results suggest that DOE confers resistance to LPS-triggered inflammation through NO-mediated inhibitory effects on HMGB1 release.
authors.affiliation: College of Animal Bioscience & Technology, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Korea.
authors.forename: Hyuk Soo
authors.initials: HS
authors.lastname: Choi
authors.affiliation: Department of Veternary Pharmacology and Toxicology, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Korea.
authors.forename: Jin-A
authors.initials: JA
authors.lastname: Park
authors.affiliation: College of Animal Bioscience & Technology, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Korea.
authors.forename: Jung Seok
authors.initials: JS
authors.lastname: Hwang
authors.affiliation: College of Animal Bioscience & Technology, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Korea.
authors.forename: Sun Ah
authors.initials: SA
authors.lastname: Ham
authors.affiliation: College of Animal Bioscience & Technology, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Korea.
authors.forename: Taesik
authors.initials: T
authors.lastname: Yoo
authors.affiliation: College of Animal Bioscience & Technology, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Korea.
authors.forename: Won Jin
authors.initials: WJ
authors.lastname: Lee
authors.affiliation: Department of Nursing, Semyung University, Semyung-ro, Jechon, Chungbuk, 390-711, Korea.
authors.forename: Kyung Shin
authors.initials: KS
authors.lastname: Paek
authors.affiliation: Department of Veternary Pharmacology and Toxicology, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Korea.
authors.forename: Ho-Chul
authors.initials: HC
authors.lastname: Shin
authors.affiliation: College of Animal Bioscience & Technology, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Korea.
authors.forename: Chi-Ho
authors.initials: CH
authors.lastname: Lee
authors.affiliation: College of Animal Bioscience & Technology, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Korea. hgseo@konkuk.ac.kr.
authors.forename: Han Geuk
authors.initials: HG
authors.lastname: Seo
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000302:isolation & purification / Q000627:therapeutic use*; D035782:Dalbergia / Q000737:chemistry*; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000139:chemically induced / Q000188:drug therapy*; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use*; D000067996:RAW 264.7 Cells; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D024243:HMGB1 Protein; D008070:Lipopolysaccharides; D010936:Plant Extracts; D009569:Nitric Oxide; D048031:JNK Mitogen-Activated Protein Kinases
keywords: Dalbergia Odorifera; Endotoxemia; HMGB1; Inflammation; Nitric oxide