Anti-oxidant polydatin (piceid) protects against substantia nigral motor degeneration in multiple rodent models of Parkinson’s disease

Molecular Neurodegeneration

Jiang-ping Xu²  Francesca-Fang Liao¹  Huaibin Cai⁴  Guo-hua Wang²  Ming-zi Zhang²  Chuang Wang²  Suzhen Gong¹  Bin Wang¹  Zhong Liao³  Dong-qi Zhang²  Yupin Chen² 

[1] Department of Pharmacology, University of Tennessee Health Science Center, Memphis, TN 38164, USA;Department of Pharmacology, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China;Spinal Cord Surgery, Fuzhou Second Hospital Affiliated to Xiaman University, Fuzhou 35007, China;Transgenics Section and Bioinformatics Core, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA

关键词: 6-OHDA;    MPTP;    Thioredoxin;    Rotenone;    Dopaminergic neurodegeneration;    Parkinson’s disease;    Anti-oxidants;    Oxidative stress;    Piceid;    Resveratrol derivative;   

Others  :  1160782
DOI  :  10.1186/1750-1326-10-4

 received in 2013-11-22, accepted in 2014-12-27,  发布年份 2015

【 摘 要 】

Background

Compelling evidence suggests that inhibition of the complex I of the electron transport chain and elevated oxidative stress are the earliest events during the pathogenesis of Parkinson’s disease (PD). Therefore, anti-oxidants, especially those from natural sources, hold good promise in treating PD as demonstrated mostly by the studies in rodent models.

Results

Herein, we determined if polydatin (piceid), a natural polyphenol, could exert anti-oxidative activity and attenuate dopaminergic neurodegeneration in three commonly used rodent models of PD. Male Sprague Dawley rats given rotenone subcutaneously for 5 weeks developed all the essential features of PD, including a strong increase in catalepsy score and a decrease in motor coordination activity, starting at 4 weeks. Selective increase in oxidative damage was found in the striatal region as compared to the hippocampus and cortex, accompanied by massive degeneration of dopaminergic neurons in the substantia nigra (SNc). Co-administration of piceid orally was able to attenuate rotenone-induced motor defects in a dose dependent manner, with 80 mg/kg dosage showing even better effect than L-levodopa (L-dopa). Piceid treatment significantly prevented the rotenone-induced changes in the levels of glutathione, thioredoxin, ATP, malondialdehyde (MDA) and the manganese superoxide dismutases (SOD) in striatum. Furthermore, piceid treatment rescued rotenone-induced dopaminergic neurodegeneration in the SNc region. Similar protective effect of piceid was also observed in two additional models of PD, MPTP in mice and 6-OHDA in rats, showing corrected motor functions, SOD and MDA activities as well as p-Akt and activated caspase-3 levels.

Conclusion

In three rodent models of PD, piceid preserves and corrects several major anti-oxidant pathways/parameters selectively in the affected SNc region. This implies its potent anti-oxidant activity as one major underscoring mechanism for protecting the vulnerable SNc neurodegeneration in these models. Taken together, these findings strongly suggest a therapeutic potential of piceid in treating PD.

【 授权许可】

   
2015 Chen et al.; licensee BioMed Central.

【 图 表 】

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