Ginsenoside Rk1 is a novel inhibitor of NMDA receptors in cultured rat hippocampal neurons

Nayeon Ryoo, Md Ataur Rahman, Hongik Hwang, Sung Kwon Ko, Seung Yeol Nah, Hyoung Chun Kim, Hyewhon Rhim

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Background: Ginsenoside Rk1, a saponin component isolated from heat-processed Panax ginseng Meyer, has been implicated in the regulation of antitumor and anti-inflammatory activities. Although our previous studies have demonstrated that ginsenoside Rg3 significantly attenuated the activation of NMDA receptors (NMDARs) in hippocampal neurons, the effects of ginsenosides Rg5 and Rk1, which are derived from heat-mediated dehydration of ginsenoside Rg3, on neuronal NMDARs have not yet been elucidated. Methods: We examined the regulation of NMDARs by ginsenosides Rg5 and Rk1 in cultured rat hippocampal neurons using fura-2–based calcium imaging and whole-cell patch-clamp recordings. Results: The results from our investigation showed that ginsenosides Rg3 and Rg5 inhibited NMDARs with similar potencies. However, ginsenoside Rk1 inhibited NMDARs most effectively among the five compounds (Rg3, Rg5, Rk1, Rg5/Rk1 mixture, and protopanaxadiol) tested in cultured hippocampal neurons. Its inhibition is independent of the NMDA- and glycine-binding sites, and its action seems to involve in an interaction with the polyamine-binding site of the NMDAR channel complex. Conclusion: Taken together, our results suggest that ginsenoside Rk1 might be a novel component contributable to the development of ginseng-based therapeutic treatments for neurodegenerative diseases.

Original languageEnglish
Pages (from-to)490-495
Number of pages6
JournalJournal of Ginseng Research
Issue number3
StatePublished - May 2020


  • Ginsenoside Rk1
  • Hippocampal neurons
  • Intracellular Ca
  • NMDA receptors
  • Whole-cell patch-clamp


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