Paeonolum protects against MPP(+)-induced neurotoxicity in zebrafish and PC12 cells.
BACKGROUND
Parkinson's disease (PD) is the second most common neurodegenerative disease, affecting 2% of the population aged over 65 years old. Mitochondrial defects and oxidative stress actively participate in degeneration of dopaminergic (DA) neurons in PD. Paeonolum, a main component isolated from Moutan cortex, has potent antioxidant ability. Here, we have examined the effects of paeonolum against MPP(+)-induced neurotoxicity in zebrafish and PC12 cells.


METHODS
The overall viability and neurodegeneration of DA neurons was assessed in ETvmat2:green fluorescent protein (GFP) transgenic zebrafish, in which most monoaminergic neurons are labeled by GFP. Damage to PC12 cells was measured using a cell viability assay and assessment of nuclear morphology. Intracellular reactive oxygen species (ROS) and the level of total GSH were assessed. The mitochondrial cell death pathway including mitochondrial membrane potential, cytochrome C release and caspase-3 activity were also examined in PC12 cells.


RESULTS
Paeonolum protected against MPP(+)-induced DA neurodegeneration and locomotor dysfunction in zebrafish in a concentration-dependent manner. Similar neuroprotection was replicated in the PC12 cellular model of MPP(+) toxicity. Paeonolum attenuated MPP(+)-induced intracellular ROS accumulation and restored the level of total GSH in PC12 cells. Furthermore, paeonolum significantly inhibited the mitochondrial cell death pathway induced by MPP(+).


CONCLUSIONS
Collectively, the present study demonstrates that paeonolum protects zebrafish and PC12 cells against MPP(+)-induced neurotoxicity.
Department of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. goodxilin@163.com.|National Key Clinical Department, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. goodxilin@163.com.|Key Discipline of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. goodxilin@163.com.
Xi-Lin
XL
Lu
Department of Clinical Laboratory, Cancer Center of Sun Yat-sen University, Guangzhou, 510060, China. linyh@sysucc.org.cn.
Yue-Hao
YH
Lin
Department of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. wuqi@medmail.com.cn.|National Key Clinical Department, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. wuqi@medmail.com.cn.|Key Discipline of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. wuqi@medmail.com.cn.
Qi
Q
Wu
Department of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. jisufengjuan@163.com.|National Key Clinical Department, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. jisufengjuan@163.com.|Key Discipline of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. jisufengjuan@163.com.
Feng-Juan
FJ
Su
Department of Geriatrics, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. ych201176@163.com.
Cheng-Hui
CH
Ye
Neurosurgery Intensive Care Unit, Department of Critical Care Medicine, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. shilei.victory@163.com.
Lei
L
Shi
Department of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. 709194054@qq.com.|National Key Clinical Department, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. 709194054@qq.com.|Key Discipline of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. 709194054@qq.com.
Bai-Xuan
BX
He
Department of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. 916888327@qq.com.|National Key Clinical Department, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. 916888327@qq.com.|Key Discipline of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. 916888327@qq.com.
Fei-Wen
FW
Huang
Department of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. peizhong@mail.sysu.edu.cn.|National Key Clinical Department, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. peizhong@mail.sysu.edu.cn.|Key Discipline of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. peizhong@mail.sysu.edu.cn.
Zhong
Z
Pei
Department of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. liliyao71@163.com.|National Key Clinical Department, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. liliyao71@163.com.|Key Discipline of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. liliyao71@163.com.
Xiao-Li
XL
Yao
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D020267:MPTP Poisoning / Q000378:metabolism / Q000517:prevention & control; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009498:Neurotoxins / Q000009:adverse effects; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D029596:Paeonia / Q000737:chemistry*; D010300:Parkinson Disease / Q000378:metabolism / Q000517:prevention & control*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015027:Zebrafish
D000975:Antioxidants; D018696:Neuroprotective Agents; D009498:Neurotoxins; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D045304:Cytochromes c; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D053148:Caspase 3; D004298:Dopamine