Kim, Jong-Hoon Cho, Soo Yeun Lee, Jun-Ho Jeong, Sang Min Yoon, In-Soo Lee, Byung-Hwan Lee, Joon-Hee Pyo, Mi Kyung Lee, Sang-Mok Chung, Jun-Mo Kim, Sunoh Rhim, Hyewhon Oh, Jae-Wook Nah, Seung-Yeol 2024-01-21T01:06:25Z 2024-01-21T01:06:25Z 2021-09-05 2007-03-09 0006-8993 https://pubs.kist.re.kr/handle/201004/134539 We previously demonstrated that ginsenoside Rg(3) (Rg(3)), 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 Rg(3) 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 Rg(3) on HC-induced hippocampal excitotoxicity in vitro and in vivo. Our in vitro studies using rat cultured hippocampal neurons revealed that Rg(3) treatment significantly and dose-dependently inhibited HC-induced hippocampal cell death, with an EC50 value of 28.7 +/- 7.5 mu M. Rg(3) 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 Rg(3) 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 Rg(3) against HC-induced hippocampal excitotoxicity, we examined the effect of Rg(3) on HCinduced intracellular Ca2+ elevations in cultured hippocampal cells and found that Rg(3) treatment dose-dependently inhibited HC-induced intracellular Ca2+ elevation, with an IC50) value of 41.5 +/- ITS mu M. In addition, Rg(3) treatment dose -dependently inhibited HC-induced currents in Xenopus oocytes expressing the NMDA receptor, with an IC50 of 47.3 +/- 14.2 mu M. These results collectively indicate that Rg(3)-induced neuroprotection against HC in rat hippocampus might be achieved via inhibition of HC-mediated NMDA receptor activation. (c) 2006 Elsevier B.V. All rights reserved. English ELSEVIER SCIENCE BV NEURONAL CELL-DEATH NMDA RECEPTOR IMMATURE RATS INDUCED NEUROTOXICITY CORTICAL-NEURONS DNA-DAMAGE IN-VITRO ACID BRAIN HOMOCYSTINURIA Neuroprotective effects of ginsenoside Rg(3) against homocysteine-induced excitotoxicity in rat hippocampus Article 10.1016/j.brainres.2006.12.047 1 BRAIN RESEARCH, v.1136, no.1, pp.190 - 199 BRAIN RESEARCH 1136 1 190 199 scie scopus 000244882500018 2-s2.0-33846882015 Neurosciences Neurosciences & Neurology Article NEURONAL CELL-DEATH NMDA RECEPTOR IMMATURE RATS INDUCED NEUROTOXICITY CORTICAL-NEURONS DNA-DAMAGE IN-VITRO ACID BRAIN HOMOCYSTINURIA Panax ginseng ginsenoside Rg(3) homocysteine excitotoxicity neuroprotection