Protective effects of piperine against corticosterone-induced neurotoxicity in PC12 cells

Abstract

Hyperactivation of the hypothalamic-pituitary-adrenal axis and the associated hippocampal atrophy were observed in patients with depression, which could be ameliorated by the treatment with antidepressants. Therefore, neuroprotection has been proposed to be one of the acting mechanisms of antidepressant. Our previous studies have showed that treating mice with piperine produced antidepressant-like effect in animal models of behavioral despair. This study aimed to examine the protective effect of piperine treatment on corticosterone-induced neurotoxicity in cultured rat pheochromocytoma (PC12) cells. The results showed that piperine co-treatment revealed a differential effect on the cytotoxicity of corticosterone and had its maximum inhibitory effect at 1 μM. Piperine (1 μM) co-treatment also significantly decreased intracellular reactive oxygen species level, and enhanced superoxide dismutase activity and total glutathione level in corticosterone-treated PC12 cells. In addition, piperine (1 μM) co-treatment was found to reverse the decreased brain-derived neurotrophic factor (BDNF) mRNA level caused by corticosterone in PC12 cells. The results suggest that piperine exerts a neuroprotective effect on corticosterone-induced neurotoxicity in PC12 cells, at least in part, via the inhibition of oxidative stress and the upregulation of BDNF mRNA expression. This neuroprotective effect may be one of the acting mechanisms accounts for the in vivo antidepressant activity of piperine.

Fig. 1

Effect of piperine on cell proliferation and corticosterone-induced cytotoxicity in PC12 cells. a Cell proliferation was measured by the MTS assay after being cultured with different concentrations of piperine for 48 h. b Cell survival was determined by the MTS assay. PC12 cells were treated with 200 μM corticosterone with or without different concentrations of piperine for 48 h. Values given are the mean ± SEMs (n = 6). ^# P < 0.01 as compared with the control group; *P < 0.05, **P < 0.01 as compared with the corticosterone group

Fig. 2

Effect of piperine on corticosterone-induced oxidative stress in PC12 cells. PC12 cells were treated with 1 μM piperine, 200 μM corticosterone or 1 μM piperine + 200 μM corticosterone for 48 h. Oxidative stress was assessed by measuring the intracellular ROS level (a), SOD activity (b), and total GSH level (c). Values given are the mean ± SEMs (n = 6). ^# P < 0.01 as compared with the control group; *P < 0.05, **P < 0.01 as compared with the corticosterone group

Fig. 3

Effect of piperine on BDNF mRNA level in corticosterone-treated PC12 cells. PC12 cells were treated with 1 μM piperine, 200 μM corticosterone or 1 μM piperine + 200 μM corticosterone for 48 h. BDNF mRNA level was measured by using TaqMan real-time reverse transcription-PCR analysis. Values given are the mean ± SEMs (n = 3). ^# P < 0.01 as compared with control group; **P < 0.01 as compared with corticosterone group