Effects of $(1R,9S)-{\beta}-Hydrastine$ hydrochloride on L-DOPA-Induced Cytotoxicity in PC12 cells

  • Yin, Shou-Yu (College of Pharmacy, and Research Center for Bioresource and Health, Chungbuk National University,College of Pharmacy, Yanbian University) ;
  • Lee, Jae-Joon (College of Pharmacy, and Research Center for Bioresource and Health, Chungbuk National University) ;
  • Kim, Yu-Mi (College of Pharmacy, and Research Center for Bioresource and Health, Chungbuk National University) ;
  • Jin, Chun-Mei (College of Pharmacy, and Research Center for Bioresource and Health, Chungbuk National University) ;
  • Yang, Yoo-Jung (College of Pharmacy, and Research Center for Bioresource and Health, Chungbuk National University) ;
  • Lee, Myung-Koo (College of Pharmacy, and Research Center for Bioresource and Health, Chungbuk National University)
  • Published : 2004.06.30

Abstract

Previously, $(1R,9S)-{\beta}-Hydrastine$ hydrochloride has been found to lower dopamine content in PC12 cells (Kim et al., 20001). In this study, the effects of $(1R,9S)-{\beta}-Hydrastine$ hydrochloride on L-DOPA-induced cytotoxicity in PC12 cells were investigated. Treatment with $(1R,9S)-{\beta}-Hydrastine$ hydrochloride at concentrations higher than $500\;{\mu}M$ caused cytotoxicity in PC12 cells. In addition, $(1R,9S)-{\beta}-Hydrastine$ hydrochloride at non-cytotoxic or cytotoxic concentrations significantly enhanced L-DOPA-induced cytotoxicity (L-DOPA concentration, $50\;{\mu}M$). Treatment of PC12 cells with $750\;{\mu}M$ $-1R,9S)-{\beta}-Hydrastine$ hydrochloride and $50\;{\mu}M$ L-DOPA, alone or in combination, also induced cell death via a mechanism which exhibited morphological and biochemical characteristics of apoptosis, including chromatin condensation and membrane blebbing. Exposure of PC12 cells to $(1R,9S)-{\beta}-Hydrastine$ hydrochloride, L-DOPA and $(1R,9S)-{\beta}-Hydrastine$ hydrochloride plus L-DOPA for 48 h resulted in a marked increase in the cell loss and percentage of apoptotic cells compared with exposure for 24 h. These data indicate that $(1R,9S)-{\beta}-Hydrastine$hydrochloride at higher concentration ranges aggravates L-DOPA-induced neurotoxicity cytotoxicity in PC12 cells. Therefore, it is proposed that the long-term L-DOPA therapeutic patients with $(1R,9S)-{\beta}-Hydrastine$ hydrochloride could be checked for the adverse symptoms.

Keywords

References

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