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Therapeutic potential of ginsenoside Rg3 and Rf for Huntington’s disease

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Abstract

Ginseng is a popular herbal medicine and known to have protective and therapeutic effects in various diseases. Ginsenosides are active gradients representing the diverse pharmacological efficacy of ginseng. Huntington’s disease (HD) is incurable genetic disorder associated with mutant huntingtin (mHtt) aggregation in the central nervous system. This study was conducted to investigate the effects of ginsenoside Rg3 and Rf on mHtt aggregation, cell viability, mitochondrial function, and apoptotic molecules on HD model. To investigate the effect of ginsenosides on HD, neural stem cells were isolated from the R6/2 mouse brain and used as a cellular model of HD. Nuclear aggregation of mHtt was measured by immunocytochemistry, and expressions of mitochondrial biogenesis and apoptotic molecules were investigated by western blot. As a result, the number of mHtt aggregates positive cells has decreased by ginsenoside Rg3 and Rf treatment in cellular model of HD. Mitochondrial biogenesis-related molecules such as PGC-1α and phosphorylated CREB were increased or showed increased tendency by ginsenoside Rg3 and Rf. Apoptotic molecules, p53, Bax, and cleaved caspase-3, were down-regulated by treatment of ginsenoside Rg3 and Rf. In addition, Lysotracker staining result showed that cellular lysosomal content was reduced by ginsenoside Rg3 and Rf. Given that ginsenoside Rg3 and Rf have the potential to reduce mHtt aggregation and cellular apoptosis, these ginsenosides can be possible therapeutic candidates for treating HD phenotypes.

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Funding

This work was supported by the Brain Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2016M3C7A1914002), SNUH research fund (26-2017-0030), and by a grant from the Korean Society of Ginseng funded by the Korea Ginseng Corporation (2015).

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  1. Mijung Lee and Jae-Jun Ban contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea

    Mijung Lee, Jae-Jun Ban, Bo Hee Won, Wooseok Im & Manho Kim

  2. Institute of Women’s Life Medical Science, Gangnam Severance Hospital, Seoul, South Korea

    Wooseok Im

  3. Neuroscience Research Institute, College of Medicine, Seoul National University , Seoul, South Korea

    Manho Kim

  4. Protein Metabolism and Neuroscience Dementia Research Center, College of Medicine, Seoul National University, Seoul, South Korea

    Manho Kim

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  1. Mijung Lee
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Correspondence to Wooseok Im or Manho Kim.

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Editor: Tetsuji Okamoto

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Lee, M., Ban, JJ., Won, B.H. et al. Therapeutic potential of ginsenoside Rg3 and Rf for Huntington’s disease. In Vitro Cell.Dev.Biol.-Animal 57, 641–648 (2021). https://doi.org/10.1007/s11626-021-00595-1

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