title: Anti-inflammatory coumarins from Paramignya trimera.
abstract: BACKGROUND
  Paramignya trimera (Oliv.) Burkill (Rutaceae) has been used to treat liver diseases and cancer. However, the anti-inflammatory effects of this medicinal plant and its components have not been elucidated.
  
  
  OBJECTIVE
  This study investigated chemical constituents of the P. trimera stems and evaluated anti-inflammatory effects of isolated compounds.
  
  
  METHODS
  Cytotoxicity of isolated compounds (5-40 μM) toward BV2 cells was tested using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) for 24 h. Inhibitory effects of isolated compounds (5-40 μM) on nitrite and PGE2concentrations were determined using Griess reaction and PGE2ELISA kit, respectively (pretreated with the compounds for 3 h and then stimulated for 18 h with LPS). Inhibitory effects of compounds (5-40 μM) on iNOS and COX-2 protein expression were evaluated by Western blot analysis (pretreated with the compounds for 3 h and then stimulated for 24 h with LPS).
  
  
  RESULTS
  Seven coumarins were isolated and identified as: ostruthin (1), ninhvanin (2), 8-geranyl-7-hydroxycoumarin (3), 6-(6',7'-dihydroxy-3',7'-dimethylocta-2'-enyl)-7-hydroxycoumarin (4), 6-(7-hydroperoxy-3,7-dimethylocta-2,5-dienyl)-7-hydroxycoumarin (5), 6-(2-hydroxyethyl)-2,2-dimethyl-2H-1-benzopyran (6), and luvangetin (7). Compounds 1-4 and 7 inhibited NO and PGE2production in LPS-stimulated BV2 cells, with IC50values ranging from 9.8 to 46.8 and from 9.4 to 52.8 μM, respectively. Ostruthin (1) and ninhvanin (2) were shown to suppress LPS-induced iNOS and COX-2 protein expression.
  
  
  CONCLUSIONS
  The present study provides a scientific rationale for the use of P. trimera in the prevention and treatment of neuroinflammatory diseases. Ostruthin and ninhvanin might have potential therapeutic effects and should be considered for further development as new anti-neuroinflammatory agents.
authors.affiliation: a Institute of Marine Biochemistry , Vietnam Academy of Science and Technology (VAST) , Cau Giay , Hanoi , Vietnam.
authors.forename: Hoang Le
authors.initials: HL
authors.lastname: Tuan Anh
authors.affiliation: b College of Pharmacy , Wonkwang University , Iksan , Republic of Korea.
authors.forename: Dong-Cheol
authors.initials: DC
authors.lastname: Kim
authors.affiliation: b College of Pharmacy , Wonkwang University , Iksan , Republic of Korea.
authors.forename: Wonmin
authors.initials: W
authors.lastname: Ko
authors.affiliation: a Institute of Marine Biochemistry , Vietnam Academy of Science and Technology (VAST) , Cau Giay , Hanoi , Vietnam.|b College of Pharmacy , Wonkwang University , Iksan , Republic of Korea.
authors.forename: Tran Minh
authors.initials: TM
authors.lastname: Ha
authors.affiliation: a Institute of Marine Biochemistry , Vietnam Academy of Science and Technology (VAST) , Cau Giay , Hanoi , Vietnam.
authors.forename: Nguyen Xuan
authors.initials: NX
authors.lastname: Nhiem
authors.affiliation: a Institute of Marine Biochemistry , Vietnam Academy of Science and Technology (VAST) , Cau Giay , Hanoi , Vietnam.
authors.forename: Pham Hai
authors.initials: PH
authors.lastname: Yen
authors.affiliation: a Institute of Marine Biochemistry , Vietnam Academy of Science and Technology (VAST) , Cau Giay , Hanoi , Vietnam.
authors.forename: Bui Huu
authors.initials: BH
authors.lastname: Tai
authors.affiliation: c Southern Institute of Ecology , Vietnam Academy of Science and Technology (VAST) , Ho Chi Minh City , Vietnam.
authors.forename: Luu Hong
authors.initials: LH
authors.lastname: Truong
authors.affiliation: c Southern Institute of Ecology , Vietnam Academy of Science and Technology (VAST) , Ho Chi Minh City , Vietnam.
authors.forename: Vu Ngoc
authors.initials: VN
authors.lastname: Long
authors.affiliation: d Khanh Hoa Association for Conservation of Nature and Environment , Khanh Hoa , Vietnam.
authors.forename: Tran
authors.initials: T
authors.lastname: Gioi
authors.affiliation: a Institute of Marine Biochemistry , Vietnam Academy of Science and Technology (VAST) , Cau Giay , Hanoi , Vietnam.|b College of Pharmacy , Wonkwang University , Iksan , Republic of Korea.
authors.forename: Tran
authors.initials: T
authors.lastname: Hong Quang
authors.affiliation: a Institute of Marine Biochemistry , Vietnam Academy of Science and Technology (VAST) , Cau Giay , Hanoi , Vietnam.
authors.forename: Chau Van
authors.initials: CV
authors.lastname: Minh
authors.affiliation: b College of Pharmacy , Wonkwang University , Iksan , Republic of Korea.
authors.forename: Hyuncheol
authors.initials: H
authors.lastname: Oh
authors.affiliation: b College of Pharmacy , Wonkwang University , Iksan , Republic of Korea.
authors.forename: Youn-Chul
authors.initials: YC
authors.lastname: Kim
authors.affiliation: a Institute of Marine Biochemistry , Vietnam Academy of Science and Technology (VAST) , Cau Giay , Hanoi , Vietnam.
authors.forename: Phan Van
authors.initials: PV
authors.lastname: Kiem
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D003374:Coumarins / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D018547:Plant Stems; D027821:Rutaceae
chemical_list: D000893:Anti-Inflammatory Agents; D003374:Coumarins; D018836:Inflammation Mediators; D010936:Plant Extracts
keywords: 6-(2-hydroxyethyl)-2,2-dimethyl-2H-1-benzopyran; 6-(6′,7′-dihydroxy-3′,7′-dimethylocta-2′-enyl)-7-hydroxycoumarin; 6-(7-hydroperoxy-3,7-dimethylocta-2,5-dienyl)-7-hydroxycoumarin; 8-geranyl-7-hydroxycoumarin; BV2 microglia; Rutaceae; luvangetin; ninhvanin; ostruthin