title: Anti-oxidant polydatin (piceid) protects against substantia nigral motor degeneration in multiple rodent models of Parkinson's disease.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China. ychen70@uthsc.edu.
authors.forename: Yupin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China. dqzhang@yahoo.com.
authors.forename: Dong-qi
authors.initials: DQ
authors.lastname: Zhang
authors.affiliation: Spinal Cord Surgery, Fuzhou Second Hospital Affiliated to Xiaman University, Fuzhou, 35007, China. zhongliao@yahoo.com.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Liao
authors.affiliation: Department of Pharmacology, University of Tennessee Health Science Center, Memphis, TN, 38164, USA. bwang10@uthsc.edu.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, University of Tennessee Health Science Center, Memphis, TN, 38164, USA. sgong@uthsc.edu.
authors.forename: Suzhen
authors.initials: S
authors.lastname: Gong
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China. cwang7@gmail.com.
authors.forename: Chuang
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China. mzzhang@yahoo.com.
authors.forename: Ming-zi
authors.initials: MZ
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China. ghwang32@gmail.com.
authors.forename: Guo-hua
authors.initials: GH
authors.lastname: Wang
authors.affiliation: Transgenics Section and Bioinformatics Core, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, 20892, USA. caih@mail.nih.gov.
authors.forename: Huaibin
authors.initials: H
authors.lastname: Cai
authors.affiliation: Department of Pharmacology, University of Tennessee Health Science Center, Memphis, TN, 38164, USA. fliao@uthsc.edu.
authors.forename: Francesca-Fang
authors.initials: FF
authors.lastname: Liao
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China. jpx@smu.edu.cn.
authors.forename: Jiang-ping
authors.initials: JP
authors.lastname: Xu
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000473:pathology; D005960:Glucosides / Q000494:pharmacology*; D008297:Male; D008810:Mice, Inbred C57BL; D009046:Motor Neurons / Q000187:drug effects; D009410:Nerve Degeneration; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016877:Oxidants / Q000037:antagonists & inhibitors*; D018384:Oxidative Stress / Q000502:physiology; D010300:Parkinson Disease / Q000188:drug therapy* / Q000473:pathology*; D017207:Rats, Sprague-Dawley; D013267:Stilbenes / Q000494:pharmacology*; D013378:Substantia Nigra / Q000187:drug effects* / Q000473:pathology
chemical_list: D005960:Glucosides; D018696:Neuroprotective Agents; D016877:Oxidants; D013267:Stilbenes; C058229:polydatin