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

doi:10.1016/j.jgr.2019.04.002

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

J Ginseng Res. 2020 May;44(3):490-495. doi: 10.1016/j.jgr.2019.04.002. Epub 2019 Apr 13.

Authors

Nayeon Ryoo¹, Md Ataur Rahman¹, Hongik Hwang¹, Sung Kwon Ko², Seung-Yeol Nah³, Hyoung-Chun Kim⁴, Hyewhon Rhim^{1

5}

Affiliations

¹ Center for Neuroscience, Korea Institute of Science and Technology, Seoul, Republic of Korea.
² Department of Oriental Medical Food & Nutrition, Semyung University, Jecheon, Republic of Korea.
³ Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul, Republic of Korea.
⁴ College of Pharmacy, Kangwon National University, Chuncheon, Republic of Korea.
⁵ Division of Bio-Medical Science and Technology, KIST School, Korea University of Science and Technology, Seoul, Republic of Korea.

Abstract

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.

Keywords: Ginsenoside Rk1; Hippocampal neurons; Intracellular Ca2+; NMDA receptors; Whole-cell patch-clamp.