Abstract
Neurodegenerative disorders (NDDs) are multifaceted complex disorders that have put a great health and economic burden around the globe nowadays. The multi-factorial nature of NDDs has presented a great challenge in drug discovery and continuous efforts are in progress in search of suitable therapeutic candidates. Nature has a great wealth of active principles in its lap that has cured the human population since ancient times. Natural products have revealed several benefits over conventional synthetic medications and scientists have shifted their vision towards exploring the therapeutic potentials of natural products in the past few years. The structural mimicking of natural compounds to endogenous ligands has presented them as a potential therapeutic candidate to prevent the development of NDDs. In the presented review, authors have summarized demographical facts about various NDDs including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD) and various types of sclerosis in the brain. The significant findings of new active principles of natural origin along with their therapeutic potentials on NDDs have been included. Also, a description of clinical trials and patents on natural products has been enlisted in this compilation. Although natural products have shown promising success in drug discovery against NDDs, still their use is associated with several ethical issues which need to be solved in the upcoming time.
Graphical Abstract
[http://dx.doi.org/10.3390/molecules25225277] [PMID: 33198233]
[http://dx.doi.org/10.1016/j.tips.2019.06.004] [PMID: 31320117]
[http://dx.doi.org/10.3390/ijms20112783] [PMID: 31174387]
[http://dx.doi.org/10.1016/j.drudis.2019.06.014] [PMID: 31238113]
[http://dx.doi.org/10.1016/j.compbiomed.2021.104851] [PMID: 34520990]
[http://dx.doi.org/10.2174/138161282624200625104355] [PMID: 32586237]
[http://dx.doi.org/10.3233/JAD-179912] [PMID: 29504538]
[http://dx.doi.org/10.1016/j.pneurobio.2016.07.005] [PMID: 27769868]
[http://dx.doi.org/10.3389/fnagi.2014.00206] [PMID: 25221506]
[http://dx.doi.org/10.2174/0929867328666210512005508] [PMID: 33982650]
[http://dx.doi.org/10.1111/ene.15385] [PMID: 35514071]
[PMID: 32275276]
[http://dx.doi.org/10.1186/s13023-015-0328-4] [PMID: 26338206]
[http://dx.doi.org/10.1097/WCO.0000000000000730] [PMID: 31361627]
[http://dx.doi.org/10.1016/j.canlet.2017.12.006] [PMID: 29222042]
[http://dx.doi.org/10.1038/s41582-020-0397-4] [PMID: 32939050]
[http://dx.doi.org/10.3390/molecules25245789] [PMID: 33302541]
[http://dx.doi.org/10.1001/jama.2019.22360] [PMID: 32044947]
[http://dx.doi.org/10.1038/nrdp.2017.71] [PMID: 28980624]
[http://dx.doi.org/10.1016/j.ejmech.2022.114269] [PMID: 35306287]
[http://dx.doi.org/10.1002/ptr.7099] [PMID: 33847440]
[http://dx.doi.org/10.1177/0272989X15621877] [PMID: 26683247]
[http://dx.doi.org/10.1177/0272989X19838527] [PMID: 30896330]
[http://dx.doi.org/10.3390/ijms19061578] [PMID: 29799486]
[http://dx.doi.org/10.1101/cshperspect.a028035] [PMID: 28062563]
[http://dx.doi.org/10.2147/IJN.S200490] [PMID: 31410002]
[http://dx.doi.org/10.2174/1567205018666211208140551] [PMID: 34879800]
[http://dx.doi.org/10.1038/s41586-021-03911-7] [PMID: 34588692]
[http://dx.doi.org/10.1111/jnc.13625] [PMID: 27015757]
[http://dx.doi.org/10.2174/1386207323999201110192942] [PMID: 33176638]
[http://dx.doi.org/10.2174/1389200219666180305150256] [PMID: 29512453]
[http://dx.doi.org/10.3390/biom11040543] [PMID: 33917843]
[PMID: 34727859]
[http://dx.doi.org/10.1016/j.jep.2016.12.040] [PMID: 28017696]
[http://dx.doi.org/10.1155/2018/8590381] [PMID: 30671131]
[http://dx.doi.org/10.2174/1871527320666211119122150] [PMID: 34802410]
[http://dx.doi.org/10.1016/j.semcancer.2019.07.023] [PMID: 31374244]
[PMID: 34654977]
[http://dx.doi.org/10.2174/1570159X19666210428120514] [PMID: 33913406]
[http://dx.doi.org/10.1007/s40263-019-00661-z] [PMID: 31473980]
[http://dx.doi.org/10.1016/j.parkreldis.2016.12.003] [PMID: 27979722]
[http://dx.doi.org/10.1080/14656566.2020.1787379] [PMID: 32640853]
[http://dx.doi.org/10.1016/j.biopha.2019.109670] [PMID: 31810131]
[http://dx.doi.org/10.2174/1570159X16666180419141613] [PMID: 29676231]
[http://dx.doi.org/10.1016/j.exger.2017.02.004] [PMID: 28223223]
[http://dx.doi.org/10.3389/fphar.2021.640758] [PMID: 34349640]
[http://dx.doi.org/10.1039/C6RA00302H]
[http://dx.doi.org/10.2174/1389450117666151209123402] [PMID: 26648064]
[http://dx.doi.org/10.1080/14786419.2017.1350669] [PMID: 28691859]
[http://dx.doi.org/10.3892/ijmm.2014.1656] [PMID: 24535622]
[http://dx.doi.org/10.1016/j.nbd.2018.08.010] [PMID: 30149183]
[http://dx.doi.org/10.2174/1389450123666220303094752] [PMID: 35240956]
[http://dx.doi.org/10.1371/journal.pone.0134142] [PMID: 26225560]
[http://dx.doi.org/10.1016/B978-0-12-809593-5.00006-9]
[http://dx.doi.org/10.3390/biom9110719] [PMID: 31717470]
[http://dx.doi.org/10.3390/antiox9090902] [PMID: 32971922]
[http://dx.doi.org/10.1111/cns.12684] [PMID: 28317317]
[http://dx.doi.org/10.1016/j.bioorg.2020.103722] [PMID: 32155491]
[http://dx.doi.org/10.1016/j.phymed.2019.152967] [PMID: 31154274]
[http://dx.doi.org/10.3389/fphar.2018.00346] [PMID: 29755345]
[http://dx.doi.org/10.1016/j.pharep.2019.06.002] [PMID: 31605892]
[http://dx.doi.org/10.1016/j.phymed.2019.152842] [PMID: 31048127]
[http://dx.doi.org/10.1097/JCMA.0000000000000151] [PMID: 31305343]
[http://dx.doi.org/10.3390/molecules26216531] [PMID: 34770940]
[http://dx.doi.org/10.3389/fphar.2021.681532] [PMID: 34526893]
[http://dx.doi.org/10.1016/j.jnutbio.2019.05.009] [PMID: 31207354]
[http://dx.doi.org/10.1186/s43088-022-00196-1] [PMID: 35127957]
[PMID: 34092198]
[http://dx.doi.org/10.1007/s12640-019-00120-z] [PMID: 31654381]
[http://dx.doi.org/10.1080/1028415X.2020.1721645] [PMID: 32093571]
[http://dx.doi.org/10.1007/s11064-022-03549-5] [PMID: 35150419]
[http://dx.doi.org/10.1038/s41398-020-00918-y] [PMID: 32661266]
[http://dx.doi.org/10.1186/s41983-019-0094-7]
[http://dx.doi.org/10.1042/BSR20191796] [PMID: 32537633]
[http://dx.doi.org/10.1556/018.69.2018.2.1] [PMID: 29888671]
[http://dx.doi.org/10.1016/B978-0-12-814774-0.00014-1]
[http://dx.doi.org/10.3390/molecules26175377] [PMID: 34500810]
[http://dx.doi.org/10.3390/molecules25225243] [PMID: 33187049]
[http://dx.doi.org/10.3390/ijms20143380] [PMID: 31295812]
[http://dx.doi.org/10.3389/fnut.2017.00036] [PMID: 28824916]
[http://dx.doi.org/10.1016/j.lfs.2018.07.017] [PMID: 30021118]
[http://dx.doi.org/10.1080/10408398.2022.2056726] [PMID: 35357240]
[http://dx.doi.org/10.1016/j.ijbiomac.2018.06.190] [PMID: 30001606]
[http://dx.doi.org/10.1016/j.compbiomed.2018.05.012] [PMID: 29860210]
[http://dx.doi.org/10.1016/j.bmcl.2021.128316] [PMID: 34391893]
[http://dx.doi.org/10.1016/j.bmcl.2022.128574] [PMID: 35065231]
[http://dx.doi.org/10.1016/j.neuropharm.2021.108831] [PMID: 34655599]
[http://dx.doi.org/10.1080/00207454.2018.1545772] [PMID: 30433834]
[http://dx.doi.org/10.1155/2019/2382563] [PMID: 31111044]
[http://dx.doi.org/10.3389/fimmu.2019.00936] [PMID: 31118933]
[http://dx.doi.org/10.1016/j.heliyon.2021.e06684] [PMID: 33898820]
[PMID: 33856270]
[http://dx.doi.org/10.3389/fnagi.2020.00119] [PMID: 32499693]
[http://dx.doi.org/10.1016/j.npep.2021.102200] [PMID: 34597878]
[http://dx.doi.org/10.1016/j.intimp.2019.105697] [PMID: 31352326]
[http://dx.doi.org/10.1016/j.cbi.2017.03.016] [PMID: 28389404]
[http://dx.doi.org/10.48022/mbl.2009.09006]
[http://dx.doi.org/10.1007/s11481-020-09933-8] [PMID: 32607691]
[http://dx.doi.org/10.1016/j.bbrc.2021.12.074] [PMID: 34959189]
[PMID: 34267346]
[http://dx.doi.org/10.1016/j.neulet.2018.10.053] [PMID: 30420334]
[http://dx.doi.org/10.1080/01480545.2018.1504961] [PMID: 30207190]
[http://dx.doi.org/10.1016/j.tox.2019.152256] [PMID: 31381935]
[PMID: 35096476]
[http://dx.doi.org/10.1016/j.comtox.2020.100148]
[http://dx.doi.org/10.3892/or.2017.5766] [PMID: 28677813]
[http://dx.doi.org/10.1038/s41598-021-02248-5] [PMID: 34824300]
[http://dx.doi.org/10.3390/ijms21020493] [PMID: 31941000]
[http://dx.doi.org/10.1016/j.lfs.2019.03.055] [PMID: 30914316]
[http://dx.doi.org/10.1002/mnfr.202000660] [PMID: 33141510]
[http://dx.doi.org/10.1016/j.lfs.2021.119964] [PMID: 34537230]
[http://dx.doi.org/10.1371/journal.pone.0258928] [PMID: 34767546]
[http://dx.doi.org/10.33448/rsd-v11i6.28542]
[http://dx.doi.org/10.18632/aging.202868] [PMID: 33878030]
[http://dx.doi.org/10.3389/fimmu.2022.943321] [PMID: 35935939]
[http://dx.doi.org/10.1016/j.ijbiomac.2021.02.210] [PMID: 33662414]
[http://dx.doi.org/10.1080/19390211.2019.1710646] [PMID: 31992104]
[http://dx.doi.org/10.1007/s11064-017-2445-z] [PMID: 29204750]
[http://dx.doi.org/10.1039/C7FO00809K] [PMID: 28714503]
[http://dx.doi.org/10.1016/j.ijbiomac.2021.05.071] [PMID: 33991558]
[http://dx.doi.org/10.1016/j.neuroscience.2018.03.008] [PMID: 29559385]
[http://dx.doi.org/10.1016/j.toxrep.2020.06.001] [PMID: 32551234]
[http://dx.doi.org/10.1007/s12640-018-9904-4] [PMID: 29687202]
[http://dx.doi.org/10.1007/s10735-021-09998-6] [PMID: 34170456]
[http://dx.doi.org/10.1515/jbcpp-2019-0270] [PMID: 32918805]
[http://dx.doi.org/10.1016/j.neulet.2020.135426] [PMID: 33075420]
[http://dx.doi.org/10.1016/j.cbi.2017.11.018] [PMID: 29191452]
[http://dx.doi.org/10.1021/acschemneuro.1c00153] [PMID: 34251185]
[http://dx.doi.org/10.2174/1567202616666191029113633] [PMID: 31660818]
[PMID: 35178203]
[http://dx.doi.org/10.3390/nu14020248] [PMID: 35057429]
[http://dx.doi.org/10.1136/jim-2016-000240] [PMID: 27521081]
[http://dx.doi.org/10.3390/molecules26103011] [PMID: 34070220]
[http://dx.doi.org/10.1007/s11011-021-00897-z] [PMID: 35048324]
[http://dx.doi.org/10.2174/0929867325666180117112610] [PMID: 29338678]
[http://dx.doi.org/10.1080/10408398.2017.1358139] [PMID: 28799796]
[http://dx.doi.org/10.3390/ijms222011248] [PMID: 34681908]
[http://dx.doi.org/10.1016/j.bbrep.2021.101035] [PMID: 34189277]
[http://dx.doi.org/10.1111/cns.13805] [PMID: 35068069]
[http://dx.doi.org/10.1016/j.neuint.2022.105297] [PMID: 35122926]
[http://dx.doi.org/10.1007/s12640-021-00362-w] [PMID: 33860897]
[http://dx.doi.org/10.1111/ejn.15324] [PMID: 34043864]
[http://dx.doi.org/10.1093/hmg/ddz247] [PMID: 31630202]
[http://dx.doi.org/10.1177/15353702211046927] [PMID: 34743577]
[http://dx.doi.org/10.2174/1871527317666180720162029] [PMID: 30033879]
[http://dx.doi.org/10.1186/s12974-021-02182-3] [PMID: 34116706]
[http://dx.doi.org/10.1002/smll.202107534] [PMID: 35182016]
[http://dx.doi.org/10.1080/1028415X.2021.1956254] [PMID: 34311678]
[http://dx.doi.org/10.1016/j.fct.2020.111323] [PMID: 32278002]
[http://dx.doi.org/10.1007/s11011-016-9929-4] [PMID: 27928694]
[http://dx.doi.org/10.1007/s12640-019-00086-y] [PMID: 31332714]
[http://dx.doi.org/10.1097/WNR.0000000000000888] [PMID: 28953092]
[http://dx.doi.org/10.1016/B978-0-12-822405-2.00017-7]
[http://dx.doi.org/10.1016/j.fitote.2021.104969] [PMID: 34147548]
[http://dx.doi.org/10.2174/1874467213666201012160401] [PMID: 33045973]
[PMID: 34567148]
[http://dx.doi.org/10.1111/1440-1681.13494] [PMID: 33686675]
[http://dx.doi.org/10.1016/j.biopha.2020.110995] [PMID: 33232931]
[http://dx.doi.org/10.1007/s11356-017-0842-0] [PMID: 29204935]
[http://dx.doi.org/10.1101/2021.08.12.456124]
[http://dx.doi.org/10.1016/j.neuint.2019.01.010] [PMID: 30639263]
[http://dx.doi.org/10.1016/j.biopha.2018.11.043] [PMID: 30463045]
[http://dx.doi.org/10.1016/j.ijbiomac.2019.08.168] [PMID: 31442505]
[http://dx.doi.org/10.2174/1570159X16666180911123341] [PMID: 30207235]
[http://dx.doi.org/10.1016/j.neures.2020.04.003] [PMID: 32333925]
[http://dx.doi.org/10.1038/s41598-022-08409-4] [PMID: 35301354]
[http://dx.doi.org/10.1016/j.jep.2011.12.023] [PMID: 22207211]
[http://dx.doi.org/10.1016/j.biopha.2018.04.045] [PMID: 29677545]
[http://dx.doi.org/10.3233/JAD-190923] [PMID: 31985464]
[http://dx.doi.org/10.1016/j.cbi.2021.109431] [PMID: 33716020]
[http://dx.doi.org/10.1089/jmf.2012.2698] [PMID: 24138168]
[http://dx.doi.org/10.1080/15548627.2021.1872187] [PMID: 33404280]
[http://dx.doi.org/10.1186/s12979-018-0132-9] [PMID: 30450117]
[http://dx.doi.org/10.1155/2020/9864370] [PMID: 33101635]
[http://dx.doi.org/10.1016/B978-0-323-43044-9.00166-7]
[http://dx.doi.org/10.3390/biom9090441] [PMID: 31480727]
[http://dx.doi.org/10.4162/nrp.2017.11.2.114] [PMID: 28386384]
[http://dx.doi.org/10.1111/ijfs.14260]
[http://dx.doi.org/10.1007/s11033-019-04801-y] [PMID: 31006097]
[http://dx.doi.org/10.2174/1389450119666180326125252] [PMID: 29577854]
[http://dx.doi.org/10.1016/B978-0-12-821710-8.00007-2]
[http://dx.doi.org/10.1016/B978-0-12-811405-6.00010-4]
[http://dx.doi.org/10.1021/acs.jafc.7b00805] [PMID: 28478680]
[http://dx.doi.org/10.1038/s41598-020-80748-6] [PMID: 33436909]
[http://dx.doi.org/10.1016/j.ejmech.2018.03.057] [PMID: 29605809]
[http://dx.doi.org/10.1615/CritRevBiomedEng.2020034302] [PMID: 33389893]
[http://dx.doi.org/10.3233/JPD-191754] [PMID: 31868679]
[http://dx.doi.org/10.1166/jbn.2021.3038] [PMID: 34167626]
[http://dx.doi.org/10.1021/acs.biomac.0c00143] [PMID: 32105465]
[http://dx.doi.org/10.1021/acsabm.9b00518] [PMID: 35021530]
[http://dx.doi.org/10.2217/nnm-2020-0239] [PMID: 33410329]
[http://dx.doi.org/10.1016/j.fct.2019.01.038] [PMID: 30738132]
[http://dx.doi.org/10.1021/acs.molpharmaceut.0c00672] [PMID: 32986435]
[http://dx.doi.org/10.1038/s41598-020-60293-y] [PMID: 32107408]
[http://dx.doi.org/10.1021/acs.molpharmaceut.0c00675] [PMID: 33084343]
[http://dx.doi.org/10.1016/j.fct.2020.111590] [PMID: 32710995]
[http://dx.doi.org/10.1007/s11356-022-19428-z] [PMID: 35230633]
[http://dx.doi.org/10.1055/s-0043-125337] [PMID: 29301146]
[http://dx.doi.org/10.1016/j.jphotobiol.2018.11.008] [PMID: 30504054]
[http://dx.doi.org/10.18433/jpps29595] [PMID: 29510799]
[http://dx.doi.org/10.1016/j.ijbiomac.2020.06.058] [PMID: 32531361]
[http://dx.doi.org/10.1039/D0TB01101K] [PMID: 32662804]
[http://dx.doi.org/10.1080/02652048.2018.1441916] [PMID: 29448848]
[http://dx.doi.org/10.3390/antiox10060887] [PMID: 34073115]
[http://dx.doi.org/10.1016/S0022-1759(02)00414-3] [PMID: 12535793]
[http://dx.doi.org/10.1016/j.cell.2010.01.025] [PMID: 20303878]
[http://dx.doi.org/10.1016/j.cell.2010.02.029] [PMID: 20303877]
[http://dx.doi.org/10.1038/nrd1034] [PMID: 12612644]
[http://dx.doi.org/10.1016/j.cell.2010.01.022] [PMID: 20303872]
[http://dx.doi.org/10.1016/j.cell.2010.03.006] [PMID: 20303867]
[http://dx.doi.org/10.1034/j.1600-065X.2000.17702.x] [PMID: 11138786]
[http://dx.doi.org/10.2165/00003495-200363010-00003] [PMID: 12487621]
[PMID: 9159205]
[http://dx.doi.org/10.3389/fimmu.2014.00491] [PMID: 25339958]
[http://dx.doi.org/10.1159/000452591] [PMID: 27871079]
[http://dx.doi.org/10.1177/09680519050110060301] [PMID: 16303096]
[http://dx.doi.org/10.1016/j.jare.2018.03.005] [PMID: 30034873]
[http://dx.doi.org/10.1038/nri3859] [PMID: 26139350]
[http://dx.doi.org/10.1016/j.archger.2003.10.001] [PMID: 15066307]
[http://dx.doi.org/10.1016/j.bbalip.2014.08.012] [PMID: 25152163]
[http://dx.doi.org/10.1016/j.otc.2010.04.003] [PMID: 20599080]
[PMID: 23757736]
[http://dx.doi.org/10.18433/J3VW2F] [PMID: 24393558]
[http://dx.doi.org/10.3390/ph3051530] [PMID: 27713316]
[http://dx.doi.org/10.1001/jama.286.8.954] [PMID: 11509060]
[http://dx.doi.org/10.1016/j.lfs.2020.117631] [PMID: 32251635]
[http://dx.doi.org/10.2174/0929867003374219] [PMID: 11032962]
[http://dx.doi.org/10.2174/138161207781368774] [PMID: 17691994]
[http://dx.doi.org/10.18433/J3T886] [PMID: 19203472]
[http://dx.doi.org/10.1021/acs.jnatprod.9b01285] [PMID: 32162523]
[http://dx.doi.org/10.1038/s41573-020-00114-z] [PMID: 33510482]
[http://dx.doi.org/10.1016/j.trac.2019.05.037]
[http://dx.doi.org/10.1080/13543776.2019.1598972] [PMID: 30902039]
[http://dx.doi.org/10.1093/jlb/lsw003] [PMID: 27774245]
[http://dx.doi.org/10.1038/d41586-020-00912-w] [PMID: 32221504]
[http://dx.doi.org/10.3390/molecules26175327] [PMID: 34500759]
[http://dx.doi.org/10.3390/ijms20205170] [PMID: 31635296]