Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Prophylactic role of Korean Red Ginseng in astrocytic mitochondrial biogenesis through HIF-1α

  • Park, Jinhong (Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University) ;
  • Lee, Minjae (Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University) ;
  • Kim, Minsu (Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University) ;
  • Moon, Sunhong (Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University) ;
  • Kim, Seunghee (Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University) ;
  • Kim, Sueun (Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University) ;
  • Koh, Seong-Ho (Department of Neurology, Hanyang University Guri Hospital) ;
  • Kim, Young-Myeong (Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University) ;
  • Choi, Yoon Kyung (Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University)
  • Received : 2021.03.02
  • Accepted : 2021.07.07
  • Published : 2022.05.01
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Abstract

Background: Korean Red Ginseng extract (KRGE) has been used as a health supplement and herbal medicine. Astrocytes are one of the key cells in the central nervous system (CNS) and have bioenergetic potential as they stimulate mitochondrial biogenesis. They play a critical role in connecting the brain vasculature and nerves in the CNS. Methods: Brain samples from KRGE-administered mice were tested using immunohistochemistry. Treatment of human brain astrocytes with KRGE was subjected to assays such as proliferation, cytotoxicity, Mitotracker, ATP production, and O2 consumption rate as well as western blotting to demonstrate the expression of proteins related to mitochondria functions. The expression of hypoxia-inducible factor-1α (HIF-1α) was diminished utilizing siRNA transfection. Results: Brain samples from KRGE-administered mice harbored an increased number of GFAP-expressing astrocytes. KRGE triggered the proliferation of astrocytes in vitro. Enhanced mitochondrial biogenesis induced by KRGE was detected using Mitotracker staining, ATP production, and O2 consumption rate assays. The expression of proteins related to mitochondrial electron transport was increased in KRGE-treated astrocytes. These effects were blocked by HIF-1α knockdown. The factors secreted from KRGE-treated astrocytes were determined, revealing the expression of various cytokines and growth factors, especially those related to angiogenesis and neurogenesis. KRGE-treated astrocyte conditioned media enhanced the differentiation of adult neural stem cells into mature neurons, increasing the migration of endothelial cells, and these effects were reduced in the background of HIF-1α knockdown. Conclusion: Our findings suggest that KRGE exhibits prophylactic potential by stimulating astrocyte mitochondrial biogenesis through HIF-1α, resulting in improved neurovascular function.

Keywords

Acknowledgement

Active form of HIF-1α overexpressing vector (pcDNA3.1/HIF-1αP402A/P564G) was thankfully provided by Dr. Gregg L. Semenza (Johns Hopkins University, USA).

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