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KMID : 0352720100340030246
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Journal of Ginseng Research
2010 Volume.34 No. 3 p.246 ~ p.253
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Neuroprotective Effects of Ginsenoside Rg₃ against 24-OH-cholesterol-induced Cytotoxicity in Cortical Neurons
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Roh Yoon-Seok
Kim Hyoung-Bae
Kang Chang-Won
Kim Bum-Seok
Nah Seung-Yeol
Kim Jong-Hoon
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Abstract
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Ginsenoside Rg₃ (Rg₃), one of the active ingredients in Panax ginseng, attenuates NMDA receptor-mediated currents in vitro and antagonizes NMDA receptors through a glycine modulatory site in rat cultured hippocampal neurons. In the present study, we examined the neuroprotective effects of Rg₃ on 24-hydroxycholesterol (24-OH-chol)-induced cytotoxicity in vitro. The results showed that Rg₃ treatment significantly and dose-dependently inhibited 24-OH-chol-induced cell death in rat cultured cort ical neurons, with an IC?? value of 28.7 ± 7.5 ㎛. Furthermore, the Rg₃ treatment not only significantly reduced DNA damage, but also dose-dependently attenuated 24-OH-chol-induced caspase-3 activity. To study the mechanisms underlying the in vitro neuroprotective effects of Rg₃ against 25-OH-chol-induced cytotoxicity, we also examined the effect of Rg₃ on intracellular Ca²? elevations in cultured neurons and found that Rg₃ treatment dose-dependently inhibited increases in intracellular Ca²?, with an IC?? value of 40.37 ± 12.88 ㎛. Additionally, Rg₃ treatment dose-dependently inhibited apoptosis with an IC?? of 47.3 ± 14.2 ㎛. Finally, after confirming the protective effect of Rg₃ using a terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay, we found that Rg₃ is an active component in ginseng-mediated neuroprotection. These results collectively indicate that Rg₃-induced neuroprotection against 24-OH-chol in rat cortical neurons might be achieved via inhibition of a 24-OH-chol-mediated Ca²? channel. This is the first report to employ cortical neurons to study the neuroprotective effects of Rg₃ against 24-OH-chol. In conclusion, Rg₃ was effective for protecting cells against 24-OH-chol-induced cytotoxicity in rat cortical neurons. This protective ability makes Rg₃ a promising agent in pathologies implicating neurodegeneration such as apoptosis or neuronal cell death.
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KEYWORD
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Ginsenoside Rg₃, Cortical neurons, 24-OH-cholesterol oxides, Excitotoxicity, Neuroprotection
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