Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Gintonin-mediated release of astrocytic vascular endothelial growth factor protects cortical astrocytes from hypoxia-induced cell damages

  • Choi, Sun-Hye (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University) ;
  • Kim, Hyeon-Joong (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University) ;
  • Cho, Hee-Jung (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University) ;
  • Park, Sang-Deuk (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University) ;
  • Lee, Na-Eun (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University) ;
  • Hwang, Sung-Hee (Department of Pharmaceutical Engineering, College of Health Sciences, Sangji University) ;
  • Rhim, Hyewon (Center for Neuroscience, Korea Institute of Science and Technology Seoul) ;
  • Kim, Hyoung-Chun (Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University) ;
  • Cho, Ik-Hyun (Department of Convergence Medical Science, College of Oriental Korean Medicine, Kyung Hee University) ;
  • Nah, Seung-Yeol (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University)
  • Received : 2018.05.02
  • Accepted : 2018.05.28
  • Published : 2019.04.15
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Abstract

Background: Gintonin is a ginseng-derived exogenous ligand of the G protein-coupled lysophosphatidic acid (LPA) receptor. We previously reported that gintonin stimulates gliotransmitter release in primary cortical astrocytes. Astrocytes play key roles in the functions of neurovascular systems. Although vascular endothelial growth factor (VEGF) is known to influence the normal growth and maintenance of cranial blood vessels and the nervous system, there is little information about the effect of gintonin on VEGF regulation in primary astrocytes, under normal and hypoxic conditions. Methods: Using primary cortical astrocytes of mice, the effects of gintonin on the release, expression, and distribution of VEGF were examined. We further investigated whether the gintonin-mediated VEGF release protects astrocytes from hypoxia. Results: Gintonin administration stimulated the release and expression of VEGF from astrocytes in a concentration- and time-dependent manner. The gintonin-mediated increase in the release of VEGF was inhibited by the LPA1/3 receptor antagonist, Ki16425; phospholipase C inhibitor, U73122; inositol 1,4,5- triphosphate receptor antagonist, 2-APB; and intracellular $Ca^{2+}$ chelator, BAPTA. Hypoxia further stimulated astrocytic VEGF release. Gintonin treatment stimulated additional VEGF release and restored cell viability that had decreased due to hypoxia, via the VEGF receptor pathway. Altogether, the regulation of VEGF release and expression and astrocytic protection mediated by gintonin under hypoxia are achieved via the LPA receptor-VEGF signaling pathways. Conclusion: The present study shows that the gintonin-mediated regulation of VEGF in cortical astrocytes might be neuroprotective against hypoxic insults and could explain the molecular basis of the beneficial effects of ginseng on the central nervous system.

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References

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