Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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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

  • Hwang, Sung-Hee (Department of Pharmaceutical Engineering, College of Health Sciences, Sangji University) ;
  • Lee, Byung-Hwan (Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University) ;
  • Choi, Sun-Hye (Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University) ;
  • Kim, Hyeon-Joong (Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University) ;
  • Won, Kyung Jong (Department of Physiology, School of Medicine, Konkuk University) ;
  • Lee, Hwan Myung (Department of Cosmetic Science, College of Natural Science, Hoseo University) ;
  • Rhim, Hyewon (Center for Neuroscience, Korea Institute of Science and Technology) ;
  • Kim, Hyoung-Chun (Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University) ;
  • Nah, Seung-Yeol (Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University)
  • Received : 2015.08.26
  • Accepted : 2015.10.19
  • Published : 2016.10.15
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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 an in vitro model 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 the in vitro effects 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. Conclusion: The gintonin-mediated proliferation, migration, and vascular-endothelial-growth-factor release in HUVECs via LPA-receptor activation may be one of in vitro mechanisms underlying ginsenginduced angiogenic and wound-healing effects.

Keywords

References

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