Prophylactic role of Korean Red Ginseng in astrocytic mitochondrial biogenesis through HIF-1α

Jinhong Park; Minjae Lee; Minsu Kim; Sunhong Moon; Seunghee Kim; Sueun Kim; Seong-Ho Koh; Young-Myeong Kim; Yoon Kyung Choi

doi:10.1016/j.jgr.2021.07.003

Prophylactic role of Korean Red Ginseng in astrocytic mitochondrial biogenesis through HIF-1α

J Ginseng Res. 2022 May;46(3):408-417. doi: 10.1016/j.jgr.2021.07.003. Epub 2021 Jul 12.

Authors

Jinhong Park¹, Minjae Lee¹, Minsu Kim¹, Sunhong Moon¹, Seunghee Kim¹, Sueun Kim¹, Seong-Ho Koh², Young-Myeong Kim³, Yoon Kyung Choi¹

Affiliations

¹ Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul, Republic of Korea.
² Department of Neurology, Hanyang University Guri Hospital, Guri, Republic of Korea.
³ Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, Republic of Korea.

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: Angiogenesis; Astrocytic mitochondrial biogenesis; Hypoxia-inducible factor-1α; Korean Red Ginseng; Neural stem cell differentiation.