J Korean Neurol Assoc.  2016 Nov;34(5):324-332. 10.17340/jkna.2016.4.6.

Inhibitory Effect of Rotundarpene on Parkinsonian Neurotoxin 1-Methyl-4-Phenylpyridinium-Induced Apoptotic Cell Death

• Han SW
• Lee CS
• Hwang IH
• Han JH
• Kim DE

• KMID: 2359443
• DOI: http://doi.org/10.17340/jkna.2016.4.6

Abstract

BACKGROUND
The extract and hemiterpene glycosides of Ilex Rotunda Thunb exert antioxidant and anti-inflammatory effects. The effect of rotundarpene on apoptosis in neuronal cells caused by the 1-methyl-4-phenylpyridinium (MPP⁺) has not been reported previously.
METHODS
Using differentiated PC12 cells and human neuroblastoma SH-SY5Y cells, we investigated the effect of rotundarpene on MPP⁺-caused apoptosis in relation to the cell death process.
RESULTS
MPP⁺-induced cell death was identified using the MTT and neutral red uptake tests. Apoptosis was induced by eliciting decreases in the cytosolic levels of Bid and Bcl-2 proteins, increases in the cytosolic levels of Bax and p53, disruption of the mitochondrial transmembrane potential, and the release of cytochrome c and the activation of caspase-8, -9, and -3 in differentiated PC12 cells and SH-SY5Y cells. Treatment with rotundarpene reduced the MPP⁺-induced changes in the levels of apoptosis-regulated proteins, formation of reactive oxygen species, depletion and oxidation of glutathione, and cell death in both PC12 and SH-SY5Y cells.
CONCLUSIONS
Rotundarpene may reduce MPP⁺-induced apoptosis in neuronal cells by suppressing the activation of the mitochondria-mediated pathway and the caspase-8 and Bid pathways. Rotundarpene appears to act by inhibiting the production of reactive oxygen species and by the depletion and oxidation of glutathione.

Keyword

Rotundarpene; 1-methyl-4-phenylpyridinium; PC12 cells; Apoptosis-regulated proteins; Protective effect

MeSH Terms

1-Methyl-4-phenylpyridinium
Animals
Apoptosis
Caspase 8
Cell Death*
Cytochromes c
Cytosol
Glutathione
Glycosides
Humans
Ilex
Membrane Potentials
Neuroblastoma
Neurons
Neutral Red
PC12 Cells
Reactive Oxygen Species
1-Methyl-4-phenylpyridinium
Caspase 8
Cytochromes c
Glutathione
Glycosides
Neutral Red
Reactive Oxygen Species