Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Neuroprotective Effects of Ginsenoside Rg3 against 24-OH-cholesterol-induced Cytotoxicity in Cortical Neurons

  • Roh, Yoon-Seok (Department of Veterinary Physiology and Department of Veterinary Pathology, College of Veterinary Medicine, Biosafety Research Institute, Chonbuk National University) ;
  • Kim, Hyoung-Bae (Department of Veterinary Physiology and Department of Veterinary Pathology, College of Veterinary Medicine, Biosafety Research Institute, Chonbuk National University) ;
  • Kang, Chang-Won (Department of Veterinary Physiology and Department of Veterinary Pathology, College of Veterinary Medicine, Biosafety Research Institute, Chonbuk National University) ;
  • Kim, Bum-Seok (Department of Veterinary Physiology and Department of Veterinary Pathology, College of Veterinary Medicine, Biosafety Research Institute, Chonbuk National University) ;
  • Nah, Seung-Yeol (Department of Physiology, College of Veterinary Medicine, Konkuk University) ;
  • Kim, Jong-Hoon (Department of Veterinary Physiology and Department of Veterinary Pathology, College of Veterinary Medicine, Biosafety Research Institute, Chonbuk National University)
  • Received : 2010.07.12
  • Accepted : 2010.08.16
  • Published : 2010.09.30
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Abstract

Ginsenoside $Rg_3$ ($Rg_3$), 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 $Rg_3$ on 24-hydroxycholesterol (24-OH-chol)-induced cytotoxicity in vitro. The results showed that $Rg_3$ treatment significantly and dose-dependently inhibited 24-OH-chol-induced cell death in rat cultured cortical neurons, with an $IC_{50}$ value of $28.7{\pm}7.5\;{\mu}m$. Furthermore, the $Rg_3$ 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 $Rg_3$ against 25-OH-chol-induced cytotoxicity, we also examined the effect of $Rg_3$ on intracellular $Ca^{2+}$ elevations in cultured neurons and found that $Rg_3$ treatment dose-dependently inhibited increases in intracellular $Ca^{2+}$, with an $IC_{50}$ value of $40.37{\pm}12.88\;{\mu}m$. Additionally, $Rg_3$ treatment dose-dependently inhibited apoptosis with an $IC_{50}$ of $47.3{\pm}14.2\;{\mu}m$. Finally, after confirming the protective effect of $Rg_3$ using a terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay, we found that $Rg_3$ is an active component in ginseng-mediated neuroprotection. These results collectively indicate that $Rg_3$-induced neuroprotection against 24-OH-chol in rat cortical neurons might be achieved via inhibition of a 24-OH-chol-mediated $Ca^{2+}$ channel. This is the first report to employ cortical neurons to study the neuroprotective effects of $Rg_3$ against 24-OH-chol. In conclusion, $Rg_3$ was effective for protecting cells against 24-OH-chol-induced cytotoxicity in rat cortical neurons. This protective ability makes $Rg_3$ a promising agent in pathologies implicating neurodegeneration such as apoptosis or neuronal cell death.

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References

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