title: Identification of cytotoxic and anti-inflammatory constituents from the bark of Toxicodendron vernicifluum (Stokes) F.A. Barkley.
abstract: BACKGROUND
  Toxicodendron vernicifluum (Stokes) F.A. Barkley (Anacardiaceae) has traditionally been used as a food supplement and in traditional herbal medicine to treat inflammatory diseases and cancers for centuries in Korea. This study was designed to isolate the bioactive constituents from the ethanol extract of Toxicodendron vernicifluum bark and evaluate their cytotoxic and anti-inflammatory activities.
  
  
  METHODS
  Bioassay-guided fractionation and chemical investigation of the ethanol extract of Toxicodendron vernicifluum bark resulted in the isolation and identification of three new polyphenols (1-3) and six flavonoids (4-9). The structures of the isolated compounds were elucidated by spectroscopic analysis, including 1D and 2D nuclear magnetic resonance (NMR) ((1)H, (13)C, COSY, HMQC and HMBC experiments), and high resolution (HR)-mass spectrometry, and their absolute configurations were further confirmed by chemical methods and circular dichroism (CD) data analysis. Compounds 1-9 were evaluated for their antiproliferative activities against four human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and HCT-15), and anti-inflammatory activities by measuring nitric oxide (NO) levels in the medium of murine microglia BV-2 cells.
  
  
  RESULTS
  The isolated compounds were characterized as in the following: three new polyphenols, rhusopolyphenols G-I (1-3) and six flavonoids including two aurones, 2-benzyl-2,3',4',6-tetrahydroxybenzo[b]furan-3(2H)-one (4), sulfuretin (5), two dihydroflavonols, (+)-(2S,3R)-fustin (6), (+)-epitaxifolin (7), one chalcone, butein (8), and one flavonol, fisetin (9). The published NMR assignments of 4 were corrected by the detailed analysis of spectroscopic data in this study. Among the tested compounds, compounds 4-9 showed antiproliferative activity against the tested cells, with IC50 values of 4.78-28.89 μM. Compounds 5 and 8 significantly inhibited NO production in lipopolysaccharide (LPS)-stimulated BV-2 cells with IC50 values of 23.37 and 11.68 μM, respectively.
  
  
  CONCLUSIONS
  Polyphenols including flavonoids were one of the main constituents of Toxicodendron vernicifluum bark, and activities demonstrated by the isolated compounds support the ethnopharmacological use of Toxicodendron vernicifluum as anti-cancer and/or anti-inflammatory agents.
authors.affiliation: Natural Products Laboratory, School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Ki Hyun
authors.initials: KH
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Gachon University, #191 Hambakmoero, Yeonsu-gu, Incheon 406-799, Republic of Korea.
authors.forename: Eunjung
authors.initials: E
authors.lastname: Moon
authors.affiliation: Korea Research Institute of Chemical Technology, Deajeon 305-600, Republic of Korea.
authors.forename: Sang Un
authors.initials: SU
authors.lastname: Choi
authors.affiliation: School of Chemical Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Changhyun
authors.initials: C
authors.lastname: Pang
authors.affiliation: College of Pharmacy, Gachon University, #191 Hambakmoero, Yeonsu-gu, Incheon 406-799, Republic of Korea.
authors.forename: Sun Yeou
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Natural Products Laboratory, School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea. Electronic address: krlee@skku.edu.
authors.forename: Kang Ro
authors.initials: KR
authors.lastname: Lee
mesh_terms: D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D024301:Plant Bark / Q000737:chemistry*; D012251:Toxicodendron / Q000737:chemistry*
chemical_list: D000893:Anti-Inflammatory Agents; D000972:Antineoplastic Agents, Phytogenic
keywords: (+)-(2S,3R)-Fustin (PubChem CID: 72282); (+)-Epitaxifolin (PubChem CID: 443758); Anacardiaceae; Anti-inflammation; Anti-tumor activity; Butein (PubChem CID: 5281222); Doxorubicin (PubChem CID: 31703); Fisetin (PubChem CID: 5281614); Flavonoids; N(G)-monomethyl-l-arginine (PubChem CID: 135242); Polyphenols; Sulfuretin (PubChem CID: 5281295); Toxicodendron vernicifluum