Abstract
Parkinson's disease (PD) is the second most prevalent progressive neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the human midbrain. Various ongoing research studies are competing to understand the pathology of PD and elucidate the mechanisms underlying neurodegeneration. Current pharmacological treatments primarily focused on improving dopamine metabolism in PD patients, despite the side effects of long-term usage. In recent years, it is recognized that oxidative stress-mediated pathways lead to neurodegeneration in the brain, which is associated with the pathophysiology of PD. The importance of oxidative stress is often less emphasized when developing potential therapeutic approaches. Natural plant antioxidants have been shown to mediate the oxidative stress-induced effects in PD, which has gained considerable attention in both in vitro and in vivo studies. Yet, clinical trials on natural polyphenol compounds are limited, restricting the potential use of these compounds as an alternative treatment for PD. Therefore, this review provides an understanding of the oxidative stress-induced effects in PD by elucidating the underlying events contributing to oxidative stress and explore the potential use of polyphenols in improving the oxidative status in PD. Preclinical findings have supported the potential of polyphenols in providing neuroprotection against oxidative stress-induced toxicity in PD. However, limiting factors, such as safety and bioavailability of polyphenols, warrant further investigations so as to make them the potential target for clinical applications in the treatment and management of PD.
Keywords: Antioxidants, parkinson's disease, polyphenols, oxidative stress, neuroprotection, bioavailability.
[http://dx.doi.org/10.1016/j.freeradbiomed.2013.01.018] [PMID: 23380027]
[http://dx.doi.org/10.1002/mds.25945] [PMID: 24976103]
[http://dx.doi.org/10.1038/nm.2165] [PMID: 20495568]
[http://dx.doi.org/10.3389/fneur.2013.00067] [PMID: 23761780]
[http://dx.doi.org/10.1016/j.bbr.2015.03.026] [PMID: 25804361]
[http://dx.doi.org/10.1016/S1474-4422(09)70068-7] [PMID: 19375664]
[http://dx.doi.org/10.1016/S0140-6736(14)61393-3] [PMID: 25904081]
[http://dx.doi.org/10.1016/j.jcomdis.2011.04.008] [PMID: 21601869]
[http://dx.doi.org/10.1016/S1474-4422(09)70238-8] [PMID: 19909913]
[http://dx.doi.org/10.1146/annurev-neuro-061010-113641] [PMID: 21469956]
[http://dx.doi.org/10.1126/science.1227157] [PMID: 23161999]
[http://dx.doi.org/10.1016/j.jns.2011.06.003] [PMID: 21689832]
[http://dx.doi.org/10.1093/brain/awp282] [PMID: 19903734]
[http://dx.doi.org/10.1146/annurev.neuro.28.061604.135718] [PMID: 16022590]
[http://dx.doi.org/10.1016/j.expneurol.2009.03.006] [PMID: 19303005]
[http://dx.doi.org/10.3410/M3-7] [PMID: 21655332]
[http://dx.doi.org/10.1212/WNL.50.5.1346] [PMID: 9595985]
[http://dx.doi.org/10.1002/mds.23732] [PMID: 21626550]
[http://dx.doi.org/10.1002/ana.23687] [PMID: 23071076]
[http://dx.doi.org/10.1126/science.6823561] [PMID: 6823561]
[http://dx.doi.org/10.1289/ehp.1002839] [PMID: 21269927]
[http://dx.doi.org/10.1007/s12035-012-8333-2] [PMID: 22933040]
[http://dx.doi.org/10.1038/81834] [PMID: 11100151]
[http://dx.doi.org/10.1016/j.nbd.2009.01.016] [PMID: 19385059]
[http://dx.doi.org/10.1186/s13024-017-0149-0] [PMID: 28118852]
[http://dx.doi.org/10.1111/jnc.13736] [PMID: 27412483]
[http://dx.doi.org/10.1007/s00415-002-1204-4] [PMID: 12375059]
[http://dx.doi.org/10.1007/s00415-010-5741-y] [PMID: 21080185]
[http://dx.doi.org/10.1371/journal.pone.0001616] [PMID: 18286173]
[http://dx.doi.org/10.1007/s00702-018-1853-9] [PMID: 29417334]
[http://dx.doi.org/10.1016/S0028-3932(03)00117-9] [PMID: 12849761]
[http://dx.doi.org/10.1007/s004150170168] [PMID: 11499649]
[http://dx.doi.org/10.1111/cns.12727] [PMID: 28872217]
[http://dx.doi.org/10.1056/NEJM200005183422004] [PMID: 10816186]
[http://dx.doi.org/10.1134/S1819712417040031]
[http://dx.doi.org/10.5607/en.2013.22.1.11] [PMID: 23585717]
[http://dx.doi.org/10.2174/1568007033482959] [PMID: 12769802]
[http://dx.doi.org/10.2174/157015909787602823] [PMID: 19721819]
[http://dx.doi.org/10.1007/s12640-015-9590-4] [PMID: 26745969]
[http://dx.doi.org/10.3390/molecules23123283] [PMID: 30544977]
[http://dx.doi.org/10.4161/oxim.2.5.9498] [PMID: 20716914]
[http://dx.doi.org/10.1155/2011/467180] [PMID: 22191013]
[http://dx.doi.org/10.1111/j.1582-4934.2010.01010.x] [PMID: 20070435]
[http://dx.doi.org/10.1016/j.freeradbiomed.2004.02.013] [PMID: 15082065]
[PMID: 24252804]
[http://dx.doi.org/10.1111/j.1471-4159.2008.05774.x] [PMID: 19012744]
[http://dx.doi.org/10.1016/j.neuint.2012.11.004] [PMID: 23159813]
[http://dx.doi.org/10.1016/j.freeradbiomed.2013.01.003] [PMID: 23328732]
[http://dx.doi.org/10.1016/j.abb.2015.01.029] [PMID: 25841340]
[http://dx.doi.org/10.1002/ana.10350] [PMID: 12402257]
[http://dx.doi.org/10.1371/journal.pone.0155058] [PMID: 27145032]
[http://dx.doi.org/10.1016/S0891-0618(02)00019-4] [PMID: 12191726]
[http://dx.doi.org/10.1523/JNEUROSCI.16-13-04135.1996] [PMID: 8753875]
[http://dx.doi.org/10.1007/BF03033137] [PMID: 12835121]
[http://dx.doi.org/10.1016/j.brainres.2007.09.028] [PMID: 18028884]
[http://dx.doi.org/10.1523/JNEUROSCI.3602-07.2008] [PMID: 18184785]
[http://dx.doi.org/10.1523/JNEUROSCI.0319-07.2007] [PMID: 17652604]
[http://dx.doi.org/10.1016/j.neulet.2010.11.019] [PMID: 21078367]
[http://dx.doi.org/10.1007/s12640-009-9001-9] [PMID: 19384584]
[http://dx.doi.org/10.1096/fj.00-0205rev] [PMID: 11099463]
[http://dx.doi.org/10.1523/JNEUROSCI.5456-13.2014] [PMID: 24920625]
[http://dx.doi.org/10.1046/j.1471-4159.1995.64020825.x] [PMID: 7830076]
[http://dx.doi.org/10.1016/j.cbi.2011.01.006] [PMID: 21238438]
[http://dx.doi.org/10.1016/S1353-8020(13)70019-1] [PMID: 24262193]
[http://dx.doi.org/10.1111/j.1749-6632.2000.tb06180.x] [PMID: 10863533]
[http://dx.doi.org/10.1074/jbc.M111.249532] [PMID: 21642436]
[http://dx.doi.org/10.1016/S0306-4522(00)00293-1] [PMID: 11068137]
[http://dx.doi.org/10.1002/mds.23384] [PMID: 21462263]
[http://dx.doi.org/10.3389/fnins.2018.00161] [PMID: 29593491]
[http://dx.doi.org/10.1007/BF03033289] [PMID: 12835101]
[http://dx.doi.org/10.1056/NEJMra1004967] [PMID: 22276824]
[http://dx.doi.org/10.1093/jn/133.5.1468S] [PMID: 12730445]
[http://dx.doi.org/10.3945/jn.108.095224] [PMID: 19022977]
[http://dx.doi.org/10.3389/fphar.2014.00176] [PMID: 25120486]
[http://dx.doi.org/10.4155/fmc.09.140] [PMID: 20161623]
[http://dx.doi.org/10.1016/j.mri.2004.10.001] [PMID: 15733784]
[http://dx.doi.org/10.1111/j.1471-4159.2010.07132.x] [PMID: 21138437]
[http://dx.doi.org/10.1093/brain/114.4.1953] [PMID: 1832073]
[http://dx.doi.org/10.1016/j.nimb.2005.01.061]
[http://dx.doi.org/10.1016/S0896-6273(03)00126-0] [PMID: 12670420]
[http://dx.doi.org/10.1186/1750-1326-9-27] [PMID: 25011704]
[http://dx.doi.org/10.1016/j.freeradbiomed.2013.01.017] [PMID: 23376471]
[http://dx.doi.org/10.1111/j.1471-4159.2009.06470.x] [PMID: 20085612]
[http://dx.doi.org/10.1016/j.neuint.2011.05.006] [PMID: 21672570]
[http://dx.doi.org/10.1042/bj20021525] [PMID: 12523938]
[http://dx.doi.org/10.1016/j.jhazmat.2014.04.054] [PMID: 24857896]
[http://dx.doi.org/10.1038/84859] [PMID: 11175792]
[http://dx.doi.org/10.1016/j.molbrainres.2005.06.002] [PMID: 16051392]
[http://dx.doi.org/10.1097/WNR.0b013e328354a1f0] [PMID: 22581044]
[http://dx.doi.org/10.1186/s13024-017-0218-4] [PMID: 29061112]
[http://dx.doi.org/10.1155/2014/360438] [PMID: 24999379]
[http://dx.doi.org/10.1371/journal.pone.0130726] [PMID: 26076361]
[http://dx.doi.org/10.1016/j.mehy.2017.02.017] [PMID: 28351498]
[http://dx.doi.org/10.1007/s00702-004-0211-2] [PMID: 15480837]
[http://dx.doi.org/10.1007/s00702-007-0789-2] [PMID: 17690948]
[http://dx.doi.org/10.1074/jbc.M105343200] [PMID: 11553618]
[http://dx.doi.org/10.1155/2016/6235641] [PMID: 27418953]
[http://dx.doi.org/10.5607/en.2015.24.4.325] [PMID: 26713080]
[http://dx.doi.org/10.1159/000485089] [PMID: 29145191]
[http://dx.doi.org/10.1254/jphs.08R01CR] [PMID: 19008644]
[http://dx.doi.org/10.1016/j.freeradbiomed.2013.05.001] [PMID: 23665395]
[PMID: 7568330]
[http://dx.doi.org/10.1002/ana.410360305] [PMID: 8080242]
[http://dx.doi.org/10.1007/BF01291884]
[http://dx.doi.org/10.1523/JNEUROSCI.3885-07.2007] [PMID: 18094238]
[http://dx.doi.org/10.1007/s00401-010-0791-x] [PMID: 21191602]
[http://dx.doi.org/10.1007/s11064-011-0471-9] [PMID: 21484266]
[http://dx.doi.org/10.1007/s11064-011-0619-7] [PMID: 21971758]
[http://dx.doi.org/10.1097/nen.0b013e31802d6da9] [PMID: 17204939]
[http://dx.doi.org/10.1016/j.mam.2011.10.006] [PMID: 22020111]
[http://dx.doi.org/10.1016/j.freeradbiomed.2008.09.001] [PMID: 18824091]
[http://dx.doi.org/10.1093/hmg/dds143] [PMID: 22513881]
[http://dx.doi.org/10.1113/jphysiol.2003.049478] [PMID: 14561818]
[http://dx.doi.org/10.1042/BJ20081386] [PMID: 19061483]
[http://dx.doi.org/10.1016/j.pneurobio.2013.04.004] [PMID: 23643800]
[http://dx.doi.org/10.1016/j.nbd.2012.10.011] [PMID: 23064436]
[http://dx.doi.org/10.1002/ana.410360612] [PMID: 7998774]
[http://dx.doi.org/10.1016/j.brainres.2007.10.061] [PMID: 18061150]
[http://dx.doi.org/10.1002/ddrr.107] [PMID: 20818732]
[http://dx.doi.org/10.1074/jbc.M210432200] [PMID: 12496265]
[http://dx.doi.org/10.1023/B:JOBB.0000041771.66775.d5] [PMID: 15377875]
[http://dx.doi.org/10.1111/j.1471-4159.2012.07836.x] [PMID: 22708893]
[http://dx.doi.org/10.1186/1742-2094-8-129] [PMID: 21975039]
[http://dx.doi.org/10.1111/j.1471-4159.2005.03042.x] [PMID: 15836612]
[http://dx.doi.org/10.1074/jbc.M401135200] [PMID: 14985362]
[http://dx.doi.org/10.1371/journal.pone.0004756] [PMID: 19270741]
[http://dx.doi.org/10.1073/pnas.0802076105] [PMID: 18687901]
[http://dx.doi.org/10.1073/pnas.0913485107] [PMID: 20194754]
[http://dx.doi.org/10.1093/hmg/ddh180] [PMID: 15198987]
[http://dx.doi.org/10.1371/journal.pone.0002455] [PMID: 18560593]
[http://dx.doi.org/10.1016/j.nbd.2010.08.027] [PMID: 20817094]
[http://dx.doi.org/10.1016/j.neulet.2014.07.045] [PMID: 25092611]
[http://dx.doi.org/10.1016/j.bbamcr.2010.08.007] [PMID: 20736035]
[http://dx.doi.org/10.1073/pnas.0911187107] [PMID: 19966284]
[http://dx.doi.org/10.1371/journal.pbio.1000298] [PMID: 20126261]
[http://dx.doi.org/10.1016/j.mcn.2012.07.008] [PMID: 22926193]
[http://dx.doi.org/10.1016/j.neuron.2016.03.038] [PMID: 27196972]
[http://dx.doi.org/10.3390/molecules15117792] [PMID: 21060289]
[http://dx.doi.org/10.1016/j.arr.2012.01.006] [PMID: 22336470]
[http://dx.doi.org/10.1038/ejcn.2010.221] [PMID: 21045839]
[http://dx.doi.org/10.1515/revneuro-2016-0004] [PMID: 27124673]
[http://dx.doi.org/10.1016/S0197-4580(02)00078-7] [PMID: 12392777]
[http://dx.doi.org/10.2174/1389450003349380] [PMID: 11475535]
[http://dx.doi.org/10.1016/S0047-6374(99)00107-4] [PMID: 10714935]
[http://dx.doi.org/10.1023/B:NERE.0000026406.64547.93] [PMID: 15202774]
[http://dx.doi.org/10.1023/A:1013971524150] [PMID: 11874207]
[http://dx.doi.org/10.1016/j.neuroscience.2012.08.004] [PMID: 22885234]
[http://dx.doi.org/10.1111/j.1460-9568.2008.06314.x] [PMID: 18662333]
[http://dx.doi.org/10.1093/aje/155.8.732] [PMID: 11943691]
[http://dx.doi.org/10.1002/mds.21706] [PMID: 17712848]
[http://dx.doi.org/10.1100/2012/923464] [PMID: 22448141]
[http://dx.doi.org/10.1111/ggi.12123] [PMID: 23879665]
[http://dx.doi.org/10.1093/jn/138.8.1578S] [PMID: 18641210]
[http://dx.doi.org/10.1046/j.1471-4159.2001.00490.x] [PMID: 11553681]
[http://dx.doi.org/10.1016/S0161-813X(02)00079-7] [PMID: 12387363]
[http://dx.doi.org/10.1016/j.jocn.2010.01.042] [PMID: 20541420]
[http://dx.doi.org/10.3945/jn.117.255034] [PMID: 28835392]
[http://dx.doi.org/10.3390/molecules15107313] [PMID: 20966876]
[http://dx.doi.org/10.1179/135100004225003897] [PMID: 15231064]
[http://dx.doi.org/10.1016/0891-5849(95)02047-0] [PMID: 8720903]
[http://dx.doi.org/10.1016/S0006-2952(97)00155-X] [PMID: 9374417]
[http://dx.doi.org/10.1007/s11010-010-0563-x] [PMID: 20730621]
[http://dx.doi.org/10.1385/JMN:24:3:401] [PMID: 15655262]
[http://dx.doi.org/10.1021/ic7022727] [PMID: 18553907]
[http://dx.doi.org/10.1155/2012/983245] [PMID: 22754573]
[http://dx.doi.org/10.1016/j.jinorgbio.2003.10.014] [PMID: 14729307]
[http://dx.doi.org/10.1007/s12264-012-1238-2] [PMID: 22622825]
[http://dx.doi.org/10.1016/j.neulet.2013.01.007] [PMID: 23328441]
[http://dx.doi.org/10.1039/c1np00051a] [PMID: 21979811]
[http://dx.doi.org/10.1016/j.pbb.2016.09.002] [PMID: 27619637]
[http://dx.doi.org/10.1016/j.bmc.2010.02.029] [PMID: 20227282]
[http://dx.doi.org/10.1096/fj.02-0566fje] [PMID: 12514113]
[http://dx.doi.org/10.1016/j.freeradbiomed.2007.11.011] [PMID: 18166164]
[http://dx.doi.org/10.1007/s11064-016-2034-6] [PMID: 27535828]
[http://dx.doi.org/10.2174/1570159X11311040006] [PMID: 24381532]
[http://dx.doi.org/10.1111/j.1471-4159.2005.03000.x] [PMID: 15773909]
[http://dx.doi.org/10.1155/2015/392169] [PMID: 26180587]
[http://dx.doi.org/10.1016/j.freeradbiomed.2010.06.002] [PMID: 20542495]
[http://dx.doi.org/10.1007/s00702-013-1000-6] [PMID: 23459926]
[http://dx.doi.org/10.1016/j.cell.2006.11.013] [PMID: 17112576]
[http://dx.doi.org/10.1159/000328516] [PMID: 21778691]
[http://dx.doi.org/10.3390/ijms15011625] [PMID: 24451142]
[http://dx.doi.org/10.1016/j.bbadis.2014.02.010] [PMID: 24582596]
[http://dx.doi.org/10.1016/j.freeradbiomed.2016.04.027] [PMID: 27126960]
[http://dx.doi.org/10.1016/j.ejphar.2008.03.008] [PMID: 18417116]
[http://dx.doi.org/10.1016/j.neuroscience.2013.01.032] [PMID: 23357119]
[http://dx.doi.org/10.1016/j.neuroscience.2016.02.055] [PMID: 26944603]
[http://dx.doi.org/10.1111/jnc.14033] [PMID: 28376279]
[http://dx.doi.org/10.1089/ars.2012.4931] [PMID: 23815406]
[http://dx.doi.org/10.1016/j.parkreldis.2008.02.011] [PMID: 18434232]
[http://dx.doi.org/10.1016/j.bbadis.2014.10.006] [PMID: 25315300]
[http://dx.doi.org/10.1016/j.trci.2018.09.002] [PMID: 31194101]
[http://dx.doi.org/10.1097/jcp.0b013e318160862c] [PMID: 18204357]
[http://dx.doi.org/10.1212/WNL.0000000000002035] [PMID: 26362286]
[http://dx.doi.org/10.1186/s12974-016-0779-0] [PMID: 28086917]
[http://dx.doi.org/10.1016/j.jpsychires.2012.03.003] [PMID: 22459264]
[http://dx.doi.org/10.3109/13651501.2013.814796] [PMID: 23808613]
[http://dx.doi.org/10.1016/S0301-0082(02)00015-1] [PMID: 12169298]
[http://dx.doi.org/10.1016/j.jns.2009.02.353] [PMID: 19286192]
[http://dx.doi.org/10.1186/alzrt146] [PMID: 23107780]
[http://dx.doi.org/10.2147/CIA.S72728] [PMID: 25506211]
[http://dx.doi.org/10.1016/j.phrs.2018.06.007] [PMID: 29890252]
[http://dx.doi.org/10.1021/jf404439b] [PMID: 24295170]
[http://dx.doi.org/10.1016/j.lfs.2016.07.021] [PMID: 27493077]
[http://dx.doi.org/10.1039/c1fo10025d] [PMID: 21779561]
[http://dx.doi.org/10.2174/1570159X14666161026151545] [PMID: 27784225]
[http://dx.doi.org/10.1016/j.freeradbiomed.2004.08.002] [PMID: 15528027]
[http://dx.doi.org/10.3390/ijms20081883] [PMID: 30995776]
[http://dx.doi.org/10.3390/nu10050642] [PMID: 29783725]
[http://dx.doi.org/10.1111/j.1749-6632.2009.05108.x] [PMID: 20146696]
[http://dx.doi.org/10.1016/j.neuint.2015.08.011] [PMID: 26315960]
[http://dx.doi.org/10.1016/j.jns.2011.02.025] [PMID: 21376343]
[http://dx.doi.org/10.2217/nnm.14.165] [PMID: 25929569]
[http://dx.doi.org/10.1007/s00210-018-1474-8] [PMID: 29411055]
[http://dx.doi.org/10.1016/j.foodres.2014.05.059]
[http://dx.doi.org/10.1016/j.neuint.2017.08.001] [PMID: 28782592]
[http://dx.doi.org/10.1016/j.neuint.2016.01.006] [PMID: 26826319]
[http://dx.doi.org/10.1007/s00280-011-1673-1] [PMID: 21603867]
[http://dx.doi.org/10.1371/journal.pone.0206536] [PMID: 30383831]
[http://dx.doi.org/10.1016/j.metabol.2014.10.030] [PMID: 25510818]
[http://dx.doi.org/10.1212/WNL.0000000000001098] [PMID: 25411441]
[http://dx.doi.org/10.1212/WNL.0000000000004609] [PMID: 29030452]
[http://dx.doi.org/10.1016/j.neuint.2013.06.005] [PMID: 23791710]
[http://dx.doi.org/10.1016/j.nut.2014.08.001] [PMID: 25592020]
[http://dx.doi.org/10.3389/fnagi.2018.00305] [PMID: 30364199]
[http://dx.doi.org/10.1007/s12264-017-0183-5] [PMID: 28936761]
[http://dx.doi.org/10.1038/srep00954] [PMID: 23233873]
[http://dx.doi.org/10.3164/jcbn.13-108] [PMID: 24894116]
[http://dx.doi.org/10.1136/bmjopen-2013-003620] [PMID: 24247326]
[http://dx.doi.org/10.1371/journal.pone.0173731] [PMID: 28319195]
[http://dx.doi.org/10.1016/j.abb.2014.04.018] [PMID: 24814373]
[http://dx.doi.org/10.1016/j.yrtph.2018.03.019] [PMID: 29580974]