4.3 Article

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

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SPRINGER
DOI: 10.1007/s11626-021-00595-1

关键词

Huntington's disease; Mutant huntingtin; Ginsenoside; Ginseng

资金

  1. Brain Research Program through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT & Future Planning [2016M3C7A1914002]
  2. SNUH research fund [26-2017-0030]
  3. Korean Society of Ginseng - Korea Ginseng Corporation

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The study found that ginsenosides Rg3 and Rf have inhibitory effects on mHtt aggregation and cellular apoptosis in the Huntington's disease cellular model, increase mitochondrial biogenesis, and reduce the expression of apoptotic molecules.
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-1 alpha 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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