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2000
Volume 25, Issue 2
  • ISSN: 1389-5575
  • E-ISSN: 1875-5607

Abstract

Background

Alpha-synuclein (α-syn) aggregation products may cause neural injury and several neurodegenerative disorders (NDs) known as α-synucleinopathies. Alkaloids are secondary metabolites present in a variety of plant species and may positively affect human health, particularly α-synucleinopathy-associated NDs.

Aim

To summarize the latest scientific data on the inhibitory properties of alkaloids in α-synucleinopathies, especially in Parkinson’s disease.

Methods

Literature search was performed using web-based databases including Web of Science, PubMed, and Scopus up to January 2024, in the English language.

Results

Harmala alkaloids, caffein, lycorine, piperin, acetylcorynoline, berberin, papaverine, squalamine, trodusquemine and nicotin have been found to be the most active natural alkaloids against synucleinopathy. The underlying mechanisms that contribute to this effect would be the inhibition of α-syn aggregation; elimination of formed aggregates; improvement in autophagy activation; promotion of the activity and expression of antioxidative enzymes; and prevention of oxidative injury and apoptosis in dopaminergic neurons.

Conclusion

The findings of the present study highlight the inhibitory activities of alkaloids against synucleinopathy. However, no clinical data supports the reported activities in humans, which calls attention to the need for conducting clinical trials to elucidate the efficacy, safety, proper dosage, unwanted effects and pharmacokinetics aspects of alkaloids in humans.

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2025-01-08
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References

  1. MhyreT.R. BoydJ.T. HamillR.W. ZeissM.K.A. Parkinson’s disease.Subcell. Biochem.20126538945510.1007/978‑94‑007‑5416‑4_16 23225012
    [Google Scholar]
  2. RizekP. KumarN. JogM.S. An update on the diagnosis and treatment of Parkinson disease.CMAJ2016188161157116510.1503/cmaj.151179 27221269
    [Google Scholar]
  3. KouliA. TorsneyK.M. KuanW-L. Parkinson’s disease: Etiology, neuropathology, and pathogenesisExon Publications: Brisbane (AU)2018326
    [Google Scholar]
  4. RamazaniE. YazdFazeli, M.; Emami, S.A.; Mohtashami, L.; Javadi, B.; Asili, J.; Najaran, T.Z. Protective effects of Cinnamomum verum, Cinnamomum cassia and cinnamaldehyde against 6-OHDA-induced apoptosis in PC12 cells.Mol. Biol. Rep.20204742437244510.1007/s11033‑020‑05284‑y 32166553
    [Google Scholar]
  5. AlexoudiA. AlexoudiI. GatzonisS. Parkinson’s disease pathogenesis, evolution and alternative pathways: A review.Rev. Neurol.20181741069970410.1016/j.neurol.2017.12.003 30131173
    [Google Scholar]
  6. KabraA. SharmaR. KabraR. BaghelU.S. Emerging and alternative therapies for Parkinson disease: An updated review.Curr. Pharm. Des.201824222573258210.2174/1381612824666180820150150 30124146
    [Google Scholar]
  7. HeimB. KrismerF. De MarziR. SeppiK. Magnetic resonance imaging for the diagnosis of Parkinson’s disease.J. Neural Transm.2017124891596410.1007/s00702‑017‑1717‑8 28378231
    [Google Scholar]
  8. LeeT.K. YankeeE.L. A review on Parkinson’s disease treatment.Neuroimmunol. Neuroinflamm.2022822210.20517/2347‑8659.2020.58
    [Google Scholar]
  9. CigaB.S. FairenD.M. KimJ.J. SingletonA.B. Genetics of Parkinson’s disease: An introspection of its journey towards precision medicine.Neurobiol. Dis.202013710478210.1016/j.nbd.2020.104782 31991247
    [Google Scholar]
  10. BenitoG.M. GranadoN. SanzG.P. MichelA. DumoulinM. MoratallaR. Modeling Parkinson’s disease with the alpha-synuclein protein.Front. Pharmacol.20201135610.3389/fphar.2020.00356 32390826
    [Google Scholar]
  11. GhaderiM.A. EmamiS.A. OliaB.M.D. JavadiB. The role of sesamin in targeting neurodegenerative disorders: A systematic review.Mini Rev. Med. Chem.202323675677010.2174/1389557522666220523112027 35616667
    [Google Scholar]
  12. GoedertM. JakesR. SpillantiniM.G. The synucleinopathies: Twenty years on.J. Parkinsons Dis.20177s1S51S6910.3233/JPD‑179005 28282814
    [Google Scholar]
  13. WongY.C. KraincD. α-synuclein toxicity in neurodegeneration: Mechanism and therapeutic strategies.Nat. Med.201723211310.1038/nm.4269 28170377
    [Google Scholar]
  14. BurréJ. The synaptic function of α-synuclein.J. Parkinsons Dis.20155469971310.3233/JPD‑150642 26407041
    [Google Scholar]
  15. PopovaB. GalkaD. Häffner, N.; Wang, D.; Schmitt, K.; Valerius, O. α-Synuclein decreases the abundance of proteasome subunits and alters ubiquitin conjugates in yeast.Cells20211092229
    [Google Scholar]
  16. LinK.J. LinK.L. ChenS.D. LiouC.W. ChuangY.C. LinH.Y. The overcrowded crossroads: Mitochondria, alpha-synuclein, and the endo-lysosomal system interaction in Parkinson’s disease. Int.J. Mo.l Sci.201920215312
    [Google Scholar]
  17. DeviL. RaghavendranV. PrabhuB.M. AvadhaniN.G. AnandatheerthavaradaH.K. Mitochondrial import and accumulation of alpha-synuclein impair complex I in human dopaminergic neuronal cultures and Parkinson disease brain.J. Biol. Chem.2008283149089910010.1074/jbc.M710012200 18245082
    [Google Scholar]
  18. RisiglioneP. ZinghirinoF. Di RosaM.C. MagrìA. MessinaA. Alpha-synuclein and mitochondrial dysfunction in parkinson’s disease: The emerging role of VDAC.Biomolecules2021115718
    [Google Scholar]
  19. TsunemiT. IshiguroY. YoroisakaA. ValdezC. MiyamotoK. IshikawaK. SaikiS. AkamatsuW. HattoriN. KraincD. Astrocytes protect human dopaminergic neurons from α-synuclein accumulation and propagation.J. Neurosci.202040458618862810.1523/JNEUROSCI.0954‑20.2020 33046546
    [Google Scholar]
  20. LashuelH.A. OverkC.R. OueslatiA. MasliahE. The many faces of α-synuclein: From structure and toxicity to therapeutic target.Nat. Rev. Neurosci.2013141384810.1038/nrn3406 23254192
    [Google Scholar]
  21. ManskeR.H.F. HolmesH.L. The alkaloids: Chemistry and physiology.Elsevier2014
    [Google Scholar]
  22. NgY.P. OrT.C.T. IpN.Y. Plant alkaloids as drug leads for Alzheimer’s disease.Neurochem. Int.20158926027010.1016/j.neuint.2015.07.018 26220901
    [Google Scholar]
  23. ChenJ.F. SchwarzschildM.A. Do caffeine and more selective adenosine A(2A) receptor antagonists protect against dopaminergic neurodegeneration in Parkinson’s disease? Parkinson.Relat Disord.202080S1S45S53
    [Google Scholar]
  24. StefanisL. α-Synuclein in Parkinson’s disease.Cold Spring Harb. Perspect. Med.201222a00939910.1101/cshperspect.a009399 22355802
    [Google Scholar]
  25. MorD.E. UgrasS.E. DanielsM.J. IschiropoulosH. Dynamic structural flexibility of α-synuclein.Neurobiol. Dis.201688667410.1016/j.nbd.2015.12.018 26747212
    [Google Scholar]
  26. BisagliaM. TrolioA. BellandaM. BergantinoE. BubaccoL. MammiS. Structure and topology of the non‐amyloid‐β component fragment of human α‐synuclein bound to micelles: Implications for the aggregation process.Protein Sci.20061561408141610.1110/ps.052048706 16731975
    [Google Scholar]
  27. SinghA. MaharanaS.K. ShuklaR. KesharwaniP. Nanotherapeutics approaches for targeting alpha synuclien protein in the management of Parkinson disease.Process Biochem.202111018119410.1016/j.procbio.2021.08.008
    [Google Scholar]
  28. EmamzadehF. Alpha-synuclein structure, functions, and interactions.J. Res. Med. Sci.20162112910.4103/1735‑1995.181989 27904575
    [Google Scholar]
  29. SrinivasanE. ChandrasekharG. ChandrasekarP. AnbarasuK. VickramA.S. KarunakaranR. RajasekaranR. SrikumarP.S. Alpha-synuclein aggregation in Parkinson’s disease.Front. Med.2021873697810.3389/fmed.2021.736978 34733860
    [Google Scholar]
  30. UlmerT.S. BaxA. ColeN.B. NussbaumR.L. Structure and dynamics of micelle-bound human α-synuclein.J. Biol. Chem.2005280109595960310.1074/jbc.M411805200 15615727
    [Google Scholar]
  31. BreydoL. WuJ.W. UverskyV.N. α-Synuclein misfolding and Parkinson’s disease.Biochim. Biophys. Acta Mol. Basis Dis.20121822226128510.1016/j.bbadis.2011.10.002
    [Google Scholar]
  32. NuberS. RajsombathM. MinakakiG. WinklerJ. MüllerC.P. EricssonM. Abrogating native α-synuclein tetramers in mice causes a L-DOPA-responsive motor syndrome closely resembling Parkinson’s disease.Neuron201810017590e510.1016/j.neuron.2018.09.014
    [Google Scholar]
  33. WangL. DasU. ScottD.A. TangY. McLeanP.J. RoyS. α-synuclein multimers cluster synaptic vesicles and attenuate recycling.Curr. Biol.201424192319232610.1016/j.cub.2014.08.027 25264250
    [Google Scholar]
  34. BabaM. NakajoS. TuP.H. TomitaT. NakayaK. LeeV.M. TrojanowskiJ.Q. IwatsuboT. Aggregation of alpha-synuclein in lewy bodies of sporadic Parkinson’s disease and dementia with lewy bodies.Am. J. Pathol.19981524879884 9546347
    [Google Scholar]
  35. AlamP. BoussetL. MelkiR. OtzenD.E. α‐synuclein oligomers and fibrils: A spectrum of species, a spectrum of toxicities.J. Neurochem.2019150552253410.1111/jnc.14808 31254394
    [Google Scholar]
  36. HaratiM. NajaranT.Z. JavadiB. Dietary flavonoids: Promising compounds for targeting α-synucleinopathy in Parkinson’s disease.PharmaNutrition20232410033410.1016/j.phanu.2023.100334
    [Google Scholar]
  37. CondeB.L.D. AcevedoR.R. Hernández, R.M.A.; Olvera, B.A.J.; Moreno, M.I.D.; Sánchez, A.R.; Schüle, B.; Crespo, G.M. Alpha-synuclein physiology and pathology: A perspective on cellular structures and organelles.Front. Neurosci.202013139910.3389/fnins.2019.01399 32038126
    [Google Scholar]
  38. ConwayK.A. RochetJ.C. BieganskiR.M. LansburyP.T.Jr Kinetic stabilization of the α-synuclein protofibril by a dopamine-α-synuclein adduct.Science200129455451346134910.1126/science.1063522 11701929
    [Google Scholar]
  39. Schulz-SchaefferW.J. The synaptic pathology of α-synuclein aggregation in dementia with Lewy bodies, Parkinson’s disease and Parkinson’s disease dementia.Acta Neuropathol.2010120213114310.1007/s00401‑010‑0711‑0 20563819
    [Google Scholar]
  40. JankovicJ. TanE.K. Parkinson’s disease: Etiopathogenesis and treatment.J. Neurol. Neurosurg. Psychiatry202091879580810.1136/jnnp‑2019‑322338 32576618
    [Google Scholar]
  41. CaloL. WegrzynowiczM. PerezS.J. SpillantiniG.M. Synaptic failure and α‐synuclein.Mov. Disord.201631216917710.1002/mds.26479 26790375
    [Google Scholar]
  42. IranshahyM. JavadiB. SahebkarA. Protective effects of functional foods against Parkinson’s disease: A narrative review on pharmacology, phytochemistry, and molecular mechanisms.Phytother. Res.20223651952198910.1002/ptr.7425 35244296
    [Google Scholar]
  43. AlecuI. BennettS.A.L. Dysregulated lipid metabolism and its role in α-synucleinopathy in Parkinson’s disease.Front. Neurosci.20191332810.3389/fnins.2019.00328 31031582
    [Google Scholar]
  44. ZhangG. XiaY. WanF. MaK. GuoX. KouL. YinS. HanC. LiuL. HuangJ. XiongN. WangT. New perspectives on roles of alpha-synuclein in Parkinson’s disease.Front. Aging Neurosci.20181037010.3389/fnagi.2018.00370 30524265
    [Google Scholar]
  45. MellandH. ArvellE.H. GordonS.L. Disorders of synaptic vesicle fusion machinery.J. Neurochem.2021157213016410.1111/jnc.15181 32916768
    [Google Scholar]
  46. De MirandaB.R. RochaE.M. CastroS.L. GreenamyreJ.T. Protection from α-Synuclein induced dopaminergic neurodegeneration by overexpression of the mitochondrial import receptor TOM20.NPJ Parkinsons Dis.202061110
    [Google Scholar]
  47. Di MaioR. BarrettP.J. HoffmanE.K. BarrettC.W. ZharikovA. BorahA. α-Synuclein binds to TOM20 and inhibits mitochondrial protein import in Parkinson’s disease.Sci. Translat. Med.20168342342ra78342ra78
    [Google Scholar]
  48. FieldsC.R. Bengoa-VergnioryN. Wade-MartinsR. Targeting alpha-synuclein as a therapy for Parkinson’s disease.Front. Mol. Neurosci.20191229910.3389/fnmol.2019.00299 31866823
    [Google Scholar]
  49. DehayB. VilaM. BezardE. BrundinP. KordowerJ.H. Alpha‐synuclein propagation: New insights from animal models.Mov. Disord.201631216116810.1002/mds.26370 26347034
    [Google Scholar]
  50. FatimaA. Rahul; Siddique, Y.H. Role of tangeritin against cognitive impairments in transgenic Drosophila model of Parkinson’s disease.Neurosci. Lett.201970511211710.1016/j.neulet.2019.04.047 31039425
    [Google Scholar]
  51. CuadradoF.A. SanchezS.D. MorianoM.A. CenjorL.E. OlmoL.V. MarcosM.A. Astrogliosis and sexually dimorphic neurodegeneration and microgliosis in the olfactory bulb in Parkinson’s disease.NPJ Parkinsons Dis.202171113
    [Google Scholar]
  52. LinK.J. LinK.L. ChenS.D. LiouC.W. ChuangY.C. LinH.Y. LinT.K. The overcrowded crossroads: Mitochondria, alpha-synuclein, and the endo-lysosomal system interaction in Parkinson’s disease.Int. J. Mol. Sci.20192021531210.3390/ijms20215312 31731450
    [Google Scholar]
  53. DzamkoN. GysbersA. PereraG. BaharA. ShankarA. GaoJ. FuY. HallidayG.M. Toll-like receptor 2 is increased in neurons in Parkinson’s disease brain and may contribute to alpha-synuclein pathology.Acta Neuropathol.2017133230331910.1007/s00401‑016‑1648‑8 27888296
    [Google Scholar]
  54. KoobA.O. PaulinoA.D. MasliahE. GFAP reactivity, apolipoprotein E redistribution and cholesterol reduction in human astrocytes treated with α-synuclein.Neurosci. Lett.20104691111410.1016/j.neulet.2009.11.034 19932737
    [Google Scholar]
  55. Alkaloids - Their importance in nature and for human life.Joanna, K., Ed.; AlkaloidsIntechOpen: Rijeka2019
    [Google Scholar]
  56. HeinrichM. MahJ. AmirkiaV. Alkaloids used as medicines: Structural phytochemistry meets biodiversity-An update and forward look.Molecules20212671836
    [Google Scholar]
  57. JohannsenK.K.L. KayserO. Tropane alkaloids: Chemistry, pharmacology, biosynthesis and production.Molecules2019244796
    [Google Scholar]
  58. UzorP.F. Alkaloids from plants with antimalarial activity: A review of recent studies.Evid. Based Complement. Alternat. Med.2020202011710.1155/2020/8749083 32104196
    [Google Scholar]
  59. Vitali SerdozL. RittgerH. FurlanelloF. BastianD. Quinidine—A legacy within the modern era of antiarrhythmic therapy.Pharmacol. Res.201914425726310.1016/j.phrs.2019.04.028 31026503
    [Google Scholar]
  60. MartinoE. CasamassimaG. CastiglioneS. CellupicaE. PantaloneS. PapagniF. RuiM. SicilianoA.M. CollinaS. Vinca alkaloids and analogues as anti-cancer agents: Looking back, peering ahead.Bioorg. Med. Chem. Lett.201828172816282610.1016/j.bmcl.2018.06.044 30122223
    [Google Scholar]
  61. ThawabtehA. JumaS. BaderM. KaramanD. ScranoL. BufoS.A. The biological activity of natural alkaloids against herbivores, cancerous cells and pathogens.Toxins20191111656
    [Google Scholar]
  62. SongC. MaJ. LiG. PanH. ZhuY. JinQ. CaiY. HanB. Natural composition and biosynthetic pathways of alkaloids in medicinal Dendrobium species.Front. Plant Sci.20221385094910.3389/fpls.2022.850949 35599884
    [Google Scholar]
  63. TzinV. GaliliG. The biosynthetic pathways for shikimate and aromatic amino acids in Arabidopsis thaliana.Arabidopsis Book20108e013210.1199/tab.0132 22303258
    [Google Scholar]
  64. Perez de SouzaL. GarbowiczK. BrotmanY. TohgeT. FernieA.R. The acetate pathway supports flavonoid and lipid biosynthesis in arabidopsis.Plant Physiol.2020182285786910.1104/pp.19.00683 31719153
    [Google Scholar]
  65. LuJ.H. TanJ.Q. DurairajanS.S.K. LiuL.F. ZhangZ.H. MaL. ShenH.M. ChanH.Y.E. LiM. Isorhynchophylline, a natural alkaloid, promotes the degradation of alpha-synuclein in neuronal cells via inducing autophagy.Autophagy2012819810810.4161/auto.8.1.18313 22113202
    [Google Scholar]
  66. GhanemS.S. FayedH.S. ZhuQ. LuJ.H. VaikathN.N. PonrajJ. Natural alkaloid compounds as inhibitors for alpha-synuclein seeded fibril formation and toxicity.Molecules20212612373610.3390/molecules26123736
    [Google Scholar]
  67. DeviS. KumarV. SinghS.K. DubeyA.K. KimJ.J. Flavonoids: Potential candidates for the treatment of neurodegenerative disorders.Biomedicines2021929910.3390/biomedicines9020099 33498503
    [Google Scholar]
  68. LimbockerR. StaatsR. ChiaS. RuggeriF.S. ManniniB. XuC.K. PerniM. CascellaR. BigiA. SasserL.R. BlockN.R. WrightA.K. KreiserR.P. CustyE.T. MeislG. ErricoS. HabchiJ. FlagmeierP. KartanasT. HollowsJ.E. NguyenL.T. LeForteK. BarbutD. KumitaJ.R. CecchiC. ZasloffM. KnowlesT.P.J. DobsonC.M. ChitiF. VendruscoloM. Squalamine and its derivatives modulate the aggregation of amyloid-β and α-synuclein and suppress the toxicity of their oligomers.Front. Neurosci.20211568002610.3389/fnins.2021.680026 34220435
    [Google Scholar]
  69. PerniM. GalvagnionC. MaltsevA. MeislG. MüllerM.B.D. ChallaP.K. KirkegaardJ.B. FlagmeierP. CohenS.I.A. CascellaR. ChenS.W. LimbockerR. SormanniP. HellerG.T. AprileF.A. CremadesN. CecchiC. ChitiF. NollenE.A.A. KnowlesT.P.J. VendruscoloM. BaxA. ZasloffM. DobsonC.M. A natural product inhibits the initiation of α-synuclein aggregation and suppresses its toxicity.Proc. Natl. Acad. Sci.20171146E1009E101710.1073/pnas.1610586114 28096355
    [Google Scholar]
  70. PerniM. FlagmeierP. LimbockerR. CascellaR. AprileF.A. GalvagnionC. HellerG.T. MeislG. ChenS.W. KumitaJ.R. ChallaP.K. KirkegaardJ.B. CohenS.I.A. ManniniB. BarbutD. NollenE.A.A. CecchiC. CremadesN. KnowlesT.P.J. ChitiF. ZasloffM. VendruscoloM. DobsonC.M. Multistep inhibition of α-synuclein aggregation and toxicity in vitro and in vivo by trodusquemine.ACS Chem. Biol.20181382308231910.1021/acschembio.8b00466 29953201
    [Google Scholar]
  71. MansonA.J. TurnerK. LeesA.J. Apomorphine monotherapy in the treatment of refractory motor complications of Parkinson’s disease: Long‐term follow‐up study of 64 patients.Mov. Disord.20021761235124110.1002/mds.10281 12465062
    [Google Scholar]
  72. HeurtauxT. KirchmeyerM. KoncinaE. FeltenP. RichartL. HuarteU.O. SchohnH. MittelbronnM. Apomorphine reduces A53T α-synuclein-induced microglial reactivity through activation of NRF2 signalling pathway.Cell. Mol. Neurobiol.20224282673269510.1007/s10571‑021‑01131‑1 34415465
    [Google Scholar]
  73. SubramaniamS.R. FederoffH.J. Targeting microglial activation states as a therapeutic avenue in Parkinson’s disease.Front. Aging Neurosci.2017917610.3389/fnagi.2017.00176 28642697
    [Google Scholar]
  74. KirchwegerB. Klein-JuniorL.C. PretschD. ChenY. CrettonS. GasperA.L. HeydenY.V. ChristenP. KirchmairJ. HenriquesA.T. RollingerJ.M. Azepine-indole alkaloids from Psychotria nemorosa Modulate 5-HT2A receptors and prevent in vivo protein toxicity in transgenic Caenorhabditis elegans.Front. Neurosci.20221682628910.3389/fnins.2022.826289 35360162
    [Google Scholar]
  75. FuR.H. WangY.C. ChenC.S. TsaiR.T. LiuS.P. ChangW.L. LinH.L. LuC.H. WeiJ.R. WangZ.W. ShyuW.C. LinS.Z. Acetylcorynoline attenuates dopaminergic neuron degeneration and α-synuclein aggregation in animal models of Parkinson’s disease.Neuropharmacology20148210812010.1016/j.neuropharm.2013.08.007 23973292
    [Google Scholar]
  76. LeemY.H. ParkJ.S. ParkJ.E. KimD.Y. KangJ.L. KimH.S. Papaverine inhibits α-synuclein aggregation by modulating neuroinflammation and matrix metalloproteinase-3 expression in the subacute MPTP/P mouse model of Parkinson’s disease.Biomed. Pharmacother.202013011057610.1016/j.biopha.2020.110576 32768884
    [Google Scholar]
  77. LeemY.H. ParkJ.S. ParkJ.E. KimD.Y. KimH.S. Papaverine exerts neuroprotective effect by inhibiting NLRP3 inflammasome activation in an MPTP-induced microglial priming mouse model challenged with LPS.Biomol. Ther.202129329530210.4062/biomolther.2021.039 33911050
    [Google Scholar]
  78. DingK. LiuL. ChengX. WangC. WangZ. Investigation on representation methods of dissolubility property of total alkaloid extract from Peganum harmala.Zhongguo Zhongyao Zazhi2010351722502253 21137330
    [Google Scholar]
  79. ZhangL. LiD. YuS. Pharmacological effects of harmine and its derivatives: A review.Arch. Pharm. Res.202043121259127510.1007/s12272‑020‑01283‑6 33206346
    [Google Scholar]
  80. DjamshidianA. ReifB.S. PoeweW. LeesA.J. Banisteriopsis caapi, a forgotten potential therapy for Parkinson’s disease?Mov. Disord. Clin. Pract.201631192610.1002/mdc3.12242 30713897
    [Google Scholar]
  81. CaiC.Z. ZhouH.F. YuanN.N. WuM.Y. LeeS.M.Y. RenJ.Y. SuH.X. LuJ.J. ChenX.P. LiM. TanJ.Q. LuJ.H. Natural alkaloid harmine promotes degradation of alpha-synuclein via PKA-mediated ubiquitin-proteasome system activation.Phytomedicine20196115284210.1016/j.phymed.2019.152842 31048127
    [Google Scholar]
  82. ZhuQ. ZhuangX. ChenJ. YuanN. ChenY. CaiC. TanJ. SuH. LuJ. Lycorine, a natural alkaloid, promotes the degradation of alpha-synuclein via PKA-mediated UPS activation in transgenic Parkinson’s disease models.Phytomedicine20218715357810.1016/j.phymed.2021.153578 34038839
    [Google Scholar]
  83. XuJ. AoY.L. HuangC. SongX. ZhangG. CuiW. WangY. ZhangX-Q. ZhangZ. Harmol promotes α-synuclein degradation and improves motor impairment in Parkinson’s models via regulating autophagy-lysosome pathway.NPJ Parkinsons Dis.20228110010.1038/s41531‑022‑00361‑4
    [Google Scholar]
  84. AbulimitiG. ZengJ. AimaitiM. LeiX. MiN. Harmol hydrochloride dihydrate induces autophagy in neuro cells and promotes the degradation of α‐Syn by Atg5/Atg12‐dependent pathway.Food Sci. Nutr.202210124371437910.1002/fsn3.3031 36514773
    [Google Scholar]
  85. DengH. MaZ. Protective effects of berberine against MPTP-induced dopaminergic neuron injury through promoting autophagy in mice.Food Funct.202112188366837510.1039/D1FO01360B 34342315
    [Google Scholar]
  86. YuL. HuX. XuR. ZhaoY. XiongL. AiJ. WangX. ChenX. BaY. XingZ. GuoC. MiS. WuX. Piperine promotes PI3K/AKT/mTOR-mediated gut-brain autophagy to degrade α-Synuclein in Parkinson’s disease rats.J. Ethnopharmacol.202432211762810.1016/j.jep.2023.117628 38158101
    [Google Scholar]
  87. HuangL. ZhongX. ZhouZ. CaiY. DengM. Piperine increases striatal levels of DA and TH and decreases α-syn and Aβ42 deposition in PDD mice by regulting autophagy: Downexpression Beclin-1 and LC3B and upexpression p62.Appl. Biol. Chem.20226514210.1186/s13765‑022‑00710‑0
    [Google Scholar]
  88. LiR. LuY. ZhangQ. LiuW. YangR. JiaoJ. LiuJ. GaoG. YangH. Piperine promotes autophagy flux by P2RX4 activation in SNCA/α-synuclein-induced Parkinson disease model.Autophagy202218355957510.1080/15548627.2021.1937897 34092198
    [Google Scholar]
  89. KardaniJ. RoyI. Understanding caffeine’s role in attenuating the toxicity of α-synuclein aggregates: Implications for risk of Parkinson’s disease.ACS Chem. Neurosci.2015691613162510.1021/acschemneuro.5b00158 26167732
    [Google Scholar]
  90. LuanY. RenX. ZhengW. ZengZ. GuoY. HouZ. GuoW. ChenX. LiF. ChenJ.F. Chronic caffeine treatment protects against α-synucleinopathy by reestablishing autophagy activity in the mouse striatum.Front. Neurosci.20181230110.3389/fnins.2018.00301 29770111
    [Google Scholar]
  91. ZhangY. WuQ. ZhangL. WangQ. YangZ. LiuJ. FengL. Caffeic acid reduces A53T α-synuclein by activating JNK/Bcl-2-mediated autophagy in vitro and improves behaviour and protects dopaminergic neurons in a mouse model of Parkinson’s disease.Pharmacol. Res.201915010453810.1016/j.phrs.2019.104538 31707034
    [Google Scholar]
  92. YanR. ZhangJ. ParkH.J. ParkE.S. OhS. ZhengH. JunnE. VoronkovM. StockJ.B. MouradianM.M. Synergistic neuroprotection by coffee components eicosanoyl-5-hydroxytryptamide and caffeine in models of Parkinson’s disease and DLB.Proc. Natl. Acad. Sci.201811551E12053E1206210.1073/pnas.1813365115 30509990
    [Google Scholar]
  93. BenowitzN.L. HukkanenJ. JacobP. III Nicotine chemistry, metabolism, kinetics and biomarkers.Handb. Exp. Pharmacol.200920091922960
    [Google Scholar]
  94. OlsenA.L. ClemensS.G. FeanyM.B. Nicotine‐mediated rescue of α‐synuclein toxicity requires synaptic vesicle glycoprotein 2 in Drosophila.Mov. Disord.202338224425510.1002/mds.29283 36416213
    [Google Scholar]
  95. BonoF. MuttiV. SavoiaP. BarbonA. BellucciA. MissaleC. FiorentiniC. Nicotine prevents alpha-synuclein accumulation in mouse and human iPSC-derived dopaminergic neurons through activation of the dopamine D3- acetylcholine nicotinic receptor heteromer.Neurobiol. Dis.201912911210.1016/j.nbd.2019.04.017 31051233
    [Google Scholar]
  96. SubramaniamS.R. MagenI. BoveN. ZhuC. LemesreV. DuttaG. EliasC.J. LesterH.A. ChesseletM.F. Chronic nicotine improves cognitive and social impairment in mice overexpressing wild type α-synuclein.Neurobiol. Dis.201811717018010.1016/j.nbd.2018.05.018 29859873
    [Google Scholar]
  97. KardaniJ. SethiR. RoyI. Nicotine slows down oligomerisation of α-synuclein and ameliorates cytotoxicity in a yeast model of Parkinson’s disease.Biochim. Biophys. Acta Mol. Basis Dis.2017186361454146310.1016/j.bbadis.2017.02.002 28167231
    [Google Scholar]
  98. LaiJ.I.C. PorcuA. RomoliB. KeislerM. ManfredssonF.P. PowellS.B. DulcisD. Nicotine-mediated recruitment of GABAergic neurons to a dopaminergic phenotype attenuates motor deficits in an alpha-synuclein Parkinson’s model.Int. J. Mol. Sci.2023244420410.3390/ijms24044204 36835612
    [Google Scholar]
  99. HuangC.Y. SivalingamK. ShibuM.A. LiaoP.H. HoT.J. KuoW.W. ChenR.J. DayC.H. ViswanadhaV.P. JuD.T. Induction of autophagy by vasicinone protects neural cells from mitochondrial dysfunction and attenuates paraquat-mediated Parkinson’s disease associated α-synuclein levels.Nutrients2020126170710.3390/nu12061707 32517337
    [Google Scholar]
  100. JingH. MaodongW. ZhenjieS. AiminL. Protective effect of aloperine on dopamine neurons of Parkinson’s disease by activating autophagy.J. Biomater. Tissue Eng.202010560260810.1166/jbt.2020.2367
    [Google Scholar]
  101. OuteiroT.F. KossD.J. ErskineD. WalkerL. AkanbiK.M. BurnD. DonaghyP. MorrisC. TaylorJ.P. ThomasA. AttemsJ. McKeithI. Dementia with Lewy bodies: An update and outlook.Mol. Neurodegener.2019141510.1186/s13024‑019‑0306‑8 30665447
    [Google Scholar]
  102. AlamS. SarkerM.M.R. AfrinS. RichiF.T. ZhaoC. ZhouJ.R. MohamedI.N. Traditional herbal medicines, bioactive metabolites, and plant products against COVID-19: Update on clinical trials and mechanism of actions.Front. Pharmacol.20211267149810.3389/fphar.2021.671498 34122096
    [Google Scholar]
  103. HussainG. RasulA. AnwarH. AzizN. RazzaqA. WeiW. AliM. LiJ. LiX. Role of plant derived alkaloids and their mechanism in neurodegenerative disorders.Int. J. Biol. Sci.201814334135710.7150/ijbs.23247 29559851
    [Google Scholar]
  104. BaliZ.K. BrusztN. KőszegiZ. NagyL.V. AtlaszT. KovácsP. Aconitum alkaloid songorine exerts potent gamma-aminobutyric acid-A receptor agonist action in vivo and effectively decreases anxiety without adverse sedative or psychomotor effects in the rat.Pharmaceutics20221410206710.3390/pharmaceutics14102067
    [Google Scholar]
  105. AryalB. RautB.K. BhattaraiS. BhandariS. TandanP. GyawaliK. SharmaK. RanabhatD. ThapaR. AryalD. OjhaA. DevkotaH.P. ParajuliN. Potential therapeutic applications of plant-derived alkaloids against inflammatory and neurodegenerative diseases.Evid. Based Complement. Alternat. Med.2022202211810.1155/2022/7299778 35310033
    [Google Scholar]
  106. KhaafiM. NajaranT.Z. JavadiB. Cinnamaldehyde as a promising dietary phytochemical against metabolic syndrome: A systematic review.Mini Rev. Med. Chem.202424335536910.2174/1389557523666230725113446 37489782
    [Google Scholar]
  107. LiS. ChengX. WangC. A review on traditional uses, phytochemistry, pharmacology, pharmacokinetics and toxicology of the genus Peganum.J. Ethnopharmacol.201720312716210.1016/j.jep.2017.03.049 28359849
    [Google Scholar]
  108. MahmoudianM. SalehianP. JalilpourH. Toxicity of peganum harmala: Review and a case report. Iran J.Pharmacol. Therap2002114
    [Google Scholar]
  109. ZiegenhagenR. HeimbergK. LampenA. ErnstH.K.I. Safety aspects of the use of isolated piperine ingested as a bolus.Foods2021109212110.3390/foods10092121 34574230
    [Google Scholar]
  110. AshrafiS. AlamS. SultanaA. RajA. EmonN.U. RichiF.T. SharminT. MoonM. ParkM.N. KimB. Papaverine: A miraculous alkaloid from opium and its multimedicinal application.Molecules2023287314910.3390/molecules28073149 37049912
    [Google Scholar]
  111. KesarwaniK. GuptaR. MukerjeeA. Bioavailability enhancers of herbal origin: An overview.Asian Pac. J. Trop. Biomed.20133425326610.1016/S2221‑1691(13)60060‑X 23620848
    [Google Scholar]
  112. KhaafiF. JavadiB. Molecular targets underlying the neuroprotective effects of boswellic acid: A systematic review.Mini Rev. Med. Chem.202323191912192510.2174/1389557523666230330113611 36998129
    [Google Scholar]
  113. MuL.H. WangB. RenH.Y. LiuP. GuoD.H. WangF.M. BaiL. GuoY.S. Synthesis and inhibitory effect of piperine derivates on monoamine oxidase.Bioorg. Med. Chem. Lett.20122293343334810.1016/j.bmcl.2012.02.090 22475561
    [Google Scholar]
  114. KongL.D. ChengC.H.K. TanR.X. Inhibition of MAO A and B by some plant-derived alkaloids, phenols and anthraquinones.J. Ethnopharmacol.2004912-335135510.1016/j.jep.2004.01.013 15120460
    [Google Scholar]
  115. HuangC.Y. SivalingamK. ShibuM.A. LiaoP.H. HoT.J. KuoW.W. Induction of autophagy by vasicinone protects neural cells from mitochondrial dysfunction and attenuates paraquat-mediated parkinson’s disease associated α-synuclein levels.Nutrients2020126170710.3390/nu12061707
    [Google Scholar]
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