title: Identification and characterization of [6]-shogaol from ginger as inhibitor of vascular smooth muscle cell proliferation.
abstract: METHODS
  Vascular smooth muscle cell (VSMC) proliferation is involved in the pathogenesis of cardiovascular disease, making the identification of new counteracting agents and their mechanisms of action relevant. Ginger and its constituents have been reported to improve cardiovascular health, but no studies exist addressing a potential interference with VSMC proliferation.
  
  
  RESULTS
  The dichloromethane extract of ginger inhibited VSMC proliferation when monitored by resazurin metabolic conversion (IC50 = 2.5 μg/mL). The examination of major constituents from ginger yielded [6]-shogaol as the most active compound (IC50 = 2.7 μM). In the tested concentration range [6]-shogaol did not exhibit cytotoxicity toward VSMC and did not interfere with endothelial cell proliferation. [6]-shogaol inhibited DNA synthesis and induced accumulation of the VSMC in the G0 /G1 cell-cycle phase accompanied with activation of the nuclear factor-erythroid 2-related factor 2 (Nrf2)/HO-1 pathway. Since [6]-shogaol lost its antiproliferative activity in the presence of the heme oxygenase-1 (HO-1) inhibitor tin protoporphyrin IX, HO-1 induction appears to contribute to the antiproliferative effect.
  
  
  CONCLUSIONS
  This study demonstrates for the first time inhibitory potential of ginger constituents on VSMC proliferation. The presented data suggest that [6]-shogaol exerts its antiproliferative effect through accumulation of cells in the G0 /G1 cell-cycle phase associated with activation of the Nrf2/HO-1 pathway.
authors: Department of Pharmacognosy, University of Vienna, Vienna, Austria; Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, P. R. China.
authors: Rongxia
authors: R
authors: Liu
authors: Elke H
authors: EH
authors: Heiss
authors: Nadine
authors: N
authors: Sider
authors: Andreas
authors: A
authors: Schinkovitz
authors: Barbara
authors: B
authors: Gröblacher
authors: Dean
authors: D
authors: Guo
authors: Franz
authors: F
authors: Bucar
authors: Rudolf
authors: R
authors: Bauer
authors: Verena M
authors: VM
authors: Dirsch
authors: Atanas G
authors: AG
authors: Atanasov
mesh_terms: D000818:Animals; D002396:Catechols / Q000302:isolation & purification* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D020939:Zingiber officinale / Q000737:chemistry*; D051547:Heme Oxygenase-1 / Q000502:physiology; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D051267:NF-E2-Related Factor 2 / Q000502:physiology; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002396:Catechols; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; C495637:Nfe2l2 protein, rat; D010936:Plant Extracts; C040115:shogaol; D051547:Heme Oxygenase-1
keywords: Ginger; Heme oxygenase-1; Nrf2; Vascular smooth muscle cell; [6]-Shogaol
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