Protective effects of paeoniflorin against glutamate-induced neurotoxicity in PC12 cells via antioxidant mechanisms and Ca(2+) antagonism.
Preclinical and clinical investigations have shown hippocampal neuronal atrophy and destruction 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. Paeoniflorin, a monoterpene glycoside, has been reported to display antidepressant-like effects in animal models of behavioral despair. The present study aimed to examine the protective effect of paeoniflorin on glutamate-induced neurotoxicity in cultured rat pheochromocytoma (PC12) cells. The results showed that pretreatment with paeoniflorin elevated cell viability, inhibited apoptosis, decreased levels of intracellular reactive oxygen species and malondialdehyde, and enhanced activity of superoxide dismutase in glutamate-treated PC12 cells. Pretreatment with paeoniflorin also reversed the increased intracellular Ca(2+) concentration and the reduced Calbindin-D28K mRNA level caused by glutamate in PC12 cells. The results suggest that paeoniflorin exerts a neuroprotective effect on glutamate-induced neurotoxicity in PC12 cells, at least in part, via inhibiting oxidative stress and Ca(2+) overload. This neuroprotective effect may be one of the action pathways accounting for the in vivo antidepressant activity of paeoniflorin.
Mao
Qing-Qiu
QQ
School of Chinese Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China. hzm1001@hotmail.com
Zhong
Xiao-Ming
XM
Feng
Chun-Rong
CR
Pan
Ai-Juan
AJ
Li
Zhao-Yi
ZY
Huang
Zhen
Z
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000928:Antidepressive Agents / Q000494:pharmacology; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D001565:Benzoates / Q000737:chemistry / Q000494:pharmacology*; D001952:Bridged-Ring Compounds / Q000737:chemistry / Q000494:pharmacology*; D064092:Calbindin 1; D064026:Calbindins; D002118:Calcium / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D005960:Glucosides / Q000737:chemistry / Q000494:pharmacology*; D018698:Glutamic Acid / Q000633:toxicity*; D006801:Humans; D008315:Malondialdehyde / Q000378:metabolism; D015394:Molecular Structure; D039821:Monoterpenes; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D020258:Neurotoxicity Syndromes; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D006027:Glycosides
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000928:Antidepressive Agents; D000975:Antioxidants; D001565:Benzoates; D001952:Bridged-Ring Compounds; D064092:Calbindin 1; D064026:Calbindins; D002118:Calcium; D005960:Glucosides; D018698:Glutamic Acid; D008315:Malondialdehyde; D039821:Monoterpenes; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D064030:S100 Calcium Binding Protein G; D013482:Superoxide Dismutase; C576498:CALB1 protein, human; C576500:Calb1 protein, rat; C015423:peoniflorin; D006027:Glycosides