title: Effects of gintonin on the proliferation, migration, and tube formation of human umbilical-vein endothelial cells: involvement of lysophosphatidic-acid receptors and vascular-endothelial-growth-factor signaling.
abstract: BACKGROUND
  Ginseng extracts are known to have angiogenic effects. However, to date, only limited information is available on the molecular mechanism underlying the angiogenic effects and the main components of ginseng that exert these effects. Human umbilical-vein endothelial cells (HUVECs) are used as anin vitromodel for screening therapeutic agents that promote angiogenesis and wound healing. We recently isolated gintonin, a novel ginseng-derived lysophosphatidic acid (LPA) receptor ligand, from ginseng. LPA plays a key role in angiogenesis and wound healing.
  
  
  METHODS
  In the present study, we investigated thein vitroeffects of gintonin on proliferation, migration, and tube formation of HUVECs, which express endogenous LPA1/3 receptors.
  
  
  RESULTS
  Gintonin stimulated proliferation and migration of HUVECs. The LPA1/3 receptor antagonist, Ki16425, short interfering RNA against LPA1 or LPA3 receptor, and the Rho kinase inhibitor, Y-27632, significantly decreased the gintonin-induced proliferation, migration, and tube formation of HUVECs, which indicates the involvement of LPA receptors and Rho kinase activation. Further, gintonin increased the release of vascular endothelial growth factors from HUVECs. The cyclooxygenase-2 inhibitor NS-398, nuclear factor kappa B inhibitor BAY11-7085, and c-Jun N-terminal kinase inhibitor SP600125 blocked the gintonin-induced migration, which shows the involvement of cyclooxygenase-2, nuclear factor kappa B, and c-Jun N-terminal kinase signaling.
  
  
  CONCLUSIONS
  The gintonin-mediated proliferation, migration, and vascular-endothelial-growth-factor release in HUVECs via LPA-receptor activation may be one ofin vitromechanisms underlying ginseng-induced angiogenic and wound-healing effects.
authors.affiliation: Department of Pharmaceutical Engineering, College of Health Sciences, Sangji University, Wonju, Korea.
authors.forename: Sung-Hee
authors.initials: SH
authors.lastname: Hwang
authors.affiliation: Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul, Korea.
authors.forename: Byung-Hwan
authors.initials: BH
authors.lastname: Lee
authors.affiliation: Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul, Korea.
authors.forename: Sun-Hye
authors.initials: SH
authors.lastname: Choi
authors.affiliation: Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul, Korea.
authors.forename: Hyeon-Joong
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Physiology, School of Medicine, Konkuk University, Chungju, Korea.
authors.forename: Kyung Jong
authors.initials: KJ
authors.lastname: Won
authors.affiliation: Department of Cosmetic Science, College of Natural Science, Hoseo University, Asan, Korea.
authors.forename: Hwan Myung
authors.initials: HM
authors.lastname: Lee
authors.affiliation: Center for Neuroscience, Korea Institute of Science and Technology, Seoul, Korea.
authors.forename: Hyewon
authors.initials: H
authors.lastname: Rhim
authors.affiliation: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, Korea.
authors.forename: Hyoung-Chun
authors.initials: HC
authors.lastname: Kim
authors.affiliation: Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul, Korea.
authors.forename: Seung-Yeol
authors.initials: SY
authors.lastname: Nah
keywords: LPA receptors; Panax ginseng; gintonin; human umbilical-vein endothelial cells