Neuroprotective effects of ginsenoside Rg3 against homocysteine-induced excitotoxicity in rat hippocampus

Jong Hoon Kim, Soo Yeun Cho, Jun Ho Lee, Sang Min Jeong, In Soo Yoon, Byung Hwan Lee, Joon Hee Lee, Mi Kyung Pyo, Sang Mok Lee, Jun Mo Chung, Sunoh Kim, Hyewhon Rhim, Jae Wook Oh, Seung Yeol Nah

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80 Scopus citations


We previously demonstrated that ginsenoside Rg3 (Rg3), one of the active ingredients in Panax ginseng, attenuates NMDA receptor-mediated currents and NMDA-induced neurotoxicity (Kim, S., Kim, T., Ahn, K., Park, W.K., Nah, S.Y., Rhim, H., 2004. Ginsenoside Rg3 antagonizes NMDA receptors through a glycine modulatory site in rat cultured hippocampal neurons. Biochem. Biophys. Res. Commun. 323, 416-424). Accumulating evidence suggests that homocysteine (HC), a metabolite of methionine, exerts its excitotoxicity through NMDA receptor activation. In the present study, we examined the neuroprotective effects of Rg3 on HC-induced hippocampal excitotoxicity in vitro and in vivo. Our in vitro studies using rat cultured hippocampal neurons revealed that Rg3 treatment significantly and dose-dependently inhibited HC-induced hippocampal cell death, with an EC50 value of 28.7 ± 7.5 μM. Rg3 treatment not only significantly reduced HC-induced DNA damage, but also dose-dependently attenuated HC-induced caspase-3 activity in vitro. Our in vivo studies revealed that intracerebroventricular (i.c.v.) pre-administration of Rg3 significantly and dose-dependently reduced i.c.v. HC-induced hippocampal damage in rats. To examine the mechanisms underlying the in vitro and in vivo neuroprotective effects of Rg3 against HC-induced hippocampal excitotoxicity, we examined the effect of Rg3 on HC-induced intracellular Ca2+ elevations in cultured hippocampal cells and found that Rg3 treatment dose-dependently inhibited HC-induced intracellular Ca2+ elevation, with an IC50 value of 41.5 ± 17.5 μM. In addition, Rg3 treatment dose-dependently inhibited HC-induced currents in Xenopus oocytes expressing the NMDA receptor, with an IC50 of 47.3 ± 14.2 μM. These results collectively indicate that Rg3-induced neuroprotection against HC in rat hippocampus might be achieved via inhibition of HC-mediated NMDA receptor activation.

Original languageEnglish
Pages (from-to)190-199
Number of pages10
JournalBrain Research
Issue number1
StatePublished - 9 Mar 2007

Bibliographical note

Funding Information:
This research was supported by the BK21 Project of the Korea Research Foundation, by grants from the Neurobiology Research Program at the Bio/Molecular Informatics Center of Konkuk University (KRF-2006-005-J03403) and by the KIST Core-Competence Program (to H. Rhim). This paper was supported by research funds of Chonbuk National University in 2006 (NP-2006-11).


  • Excitotoxicity
  • Ginsenoside Rg
  • Homocysteine
  • Neuroprotection
  • Panax ginseng


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