Piperine inhibition of 1-methyl-4-phenylpyridinium-induced mitochondrial dysfunction and cell death in PC12 cells

The effect of alkaloid piperine against the toxicity of 1-methyl-4-phenylpyridinium (MPP+) in differentiated PC12 cells was assessed. Piperine treatment revealed a differential effect on the cytotoxicity of MPP+ and had its maximum inhibitory effect at 1 μM. The addition of piperine (0.5–10 μM) significantly reduced the MPP+-induced nuclear damage, mitochondrial membrane permeability changes, formation of reactive oxygen species and depletion of GSH. In contrast, piperine at 50–100 μM showed cytotoxicity and exhibited an additive effect against the MPP+ toxicity. The results indicate that piperine had a differential effect on the cytotoxicity of MPP+ depending on concentration. Piperine at low concentrations may reduce the MPP+-induced viability loss in PC12 cells by suppressing the changes in the mitochondrial membrane permeability, leading to the release of cytochrome c and subsequent activation of caspase-3. The effects may be ascribed to its inhibitory action on the formation of reactive oxygen species and depletion of GSH.