Effects of Hydrastine Derivatives on Dopamine Biosynthesis in PC12 Cells

Abstract

The effects of hydrastine derivatives on dopamine biosynthesis in PC12 cells were investigated. Treatments of PC12 cells with (1R,9S)-β-hydrastine hydrochloride [(+)-β-hydrastine HCl] and (1R,9S)-β-hydrastine [(-)-β-hydrastine] showed 50.6 % and 33.1 % inhibition of dopamine content at a concentration of 10 μM for 48 h. However, (1S,9R)-β-hydrastine [(+)-β-hydrastine] and hydrastinine hydrochloride did not reduce dopamine content. The IC₅₀ values of (1R,9S)-β-hydrastine hydrochloride and (1R,9S)-β-hydrastine were 9.3 μM and 20.7 μM, respectively. Next, the intracellular mechanisms of (1R,9S)-β-hydrastine hydrochloride in PC12 cells were investigated. Dopamine content decreased at 6 h and reached a minimal level at 24 h after the exposure of PC12 cells to 20 μM (1R,9S)-β-hydrastine hydrochloride. Tyrosine hydroxylase (TH) activity was inhibited at 6 h following the treatment with (1R,9S)-β-hydrastine hydrochloride, and was maintained at a reduced level for up to 36 h in PC12 cells (17 - 27 % inhibition at 20 μM), whereas TH mRNA level was not found to alter for 24 h. However, the level of intracellular Ca⁺⁺ concentration decreased by treatment with (1R,9S)-β-hydrastine hydrochloride at 20 μM by 18.4 % inhibition relative to the control level in PC12 cells. These results suggest that (1R,9S)-β-hydrastine hydrochloride contributes partially to the decrease in dopamine content by the inhibition of TH activity in PC12 cells.

Key words

(1R,9S)-β-Hydrastine - (1S,9R)-β-hydrastine - Corydalis stricta - Papaveraceae - Hydrastis canadensis - Ranunculaceae - Berberis laurina - Berberidaceae - dopamine content - tyrosine hydroxylase - TH mRNA - intracellular Ca⁺⁺ concentration - PC12 cells

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