Planta Med 2016; 82(11/12): 942-951
DOI: 10.1055/s-0042-107081
Reviews
Georg Thieme Verlag KG Stuttgart · New York

Medicinal Plants and Natural Products as Potential Sources for Antiparkinson Drugs[*]

José-Luis Ríos
Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, Burjassot (Valencia), Spain
,
María Onteniente
Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, Burjassot (Valencia), Spain
,
Dolores Picazo
Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, Burjassot (Valencia), Spain
,
María-Carmen Montesinos
Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, Burjassot (Valencia), Spain
› Author Affiliations
Further Information

Publication History

received 25 February 2016
revised 05 April 2016

accepted 10 April 2016

Publication Date:
25 May 2016 (online)

Abstract

Parkinsonʼs disease is a progressive neurodegenerative dysfunction characterized by the loss of pigmented dopaminergic neurons of the nigrostriatal system with a consequent dopamine decrease. The reduction of dopamine levels produces neuronal damage, depigmentation of the substantia nigra, and the presence of intracellular inclusions in dopaminergic neurons. Treatments for Parkinsonʼs disease aim for improving these motor symptoms by increasing the dopaminergic signal in the striatum with levodopa in combination with enzyme inhibitors or anticholinergic drugs. Nevertheless, natural products can act as neuroprotective agents by reducing the progression of the disease and the inflammatory process.

In the present review, we have compiled data on the principal medicinal plants and natural products as potential antiparkinsonian agents. They act by different mechanisms, such as the inhibition of α-synuclein condensation, reduction of oxidative stress and neuro-inflammation, increase of dopaminergic neurons survival, or the blockade of the A2 A receptor.

* Dedicated to Professor Dr. Dr. h. c. mult. Kurt Hostettmann in recognition of his outstanding contribution to natural product research.


 
  • References

  • 1 Office of Communications and Public Liaison, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda MD, USA. Available at. http://www.ninds.nih.gov/disorders/parkinsons_disease/detail_parkinsons_disease.htm Accessed January 21, 2016
  • 2 Nestler EJ, Hyman SE, Malenka RC. Neurodegeration. In: Sydor A, Brown RY, editors Molecular neuropharmacology: a foundation for clinical neuroscience. 2nd edition. New York: McGraw Hill; 2009: 409-442
  • 3 Wu T, Hallett M, Chan P. Motor automaticity in Parkinsonʼs disease. Neurobiol Dis 2015; 82: 226-234
  • 4 Nagatsu T, Sawada M. L-dopa therapy for Parkinsonʼs disease: past, present, and future. Parkinsonism Relat Disord 2009; 15: S3-S8
  • 5 The Parkinson Study Group QE3 Investigators. A randomized clinical trial of high-dosage coenzyme Q10 in early Parkinsonʼs disease: No evidence of benefit. JAMA Neurol 2014; 71: 543-552
  • 6 Ross GW, Abbott RD, Petrovitch H, Morens DM, Grandinetti A, Tung KH, Tanner CM, Masaki KH, Blanchette PL, Curb JD, Popper JS, White LR. Association of coffee and caffeine intake with the risk of Parkinsonʼs disease. JAMA 2000; 283: 2674-2679
  • 7 Schapira AHV, Olanow CW, Greenamyre JT, Bezard E. Slowing of neurodegeneration in Parkinsonʼs disease and Huntingtonʼs disease: future therapeutic perspectives. Lancet 2014; 384: 545-555
  • 8 Kulisevsky J, Poyurovsky M. Adenosine A2A-receptor antagonism and pathophysiology of Parkinsonʼs disease and drug-induced movement disorders. Eur Neurol 2012; 67: 4-11
  • 9 Standaert D. Treatment of central nervous system degenerative disorders. In: Brunton LL, Chabner B, Knollman B, editors Goodman and Gilmanʼs the pharmacological basis of therapeutics, 12th edition. New York: McGraw-Hill; 2011: 609-668
  • 10 Goldman JG, Weintraub D. Advances in the treatment of cognitive impairment in Parkinsonʼs disease. Mov Disord 2015; 30: 1471-1489
  • 11 Xu K, Bastia E, Schwarzschild M. Therapeutic potential of adenosine A2A receptor antagonists in Parkinsonʼs disease. Pharmacol Ther 2005; 105: 267-310
  • 12 ClinicalTrials.gov. Investigation of Cogane (PYM50028) in early-stage Parkinsonʼs disease (CONFIDENT-PD). Available at. https://clinicaltrials.gov/ct2/show/NCT01060878 Accessed January 21, 2016
  • 13 Dias V, Junn E, Mouradian MM. The role of oxidative stress in Parkinsonʼs disease. J Parkinsons Dis 2013; 3: 461-491
  • 14 Koppula S, Kumar H, More SV, Lim HW, Hong SM, Choi DK. Recent updates in redox regulation and free radical scavenging effects by herbal products in experimental models of Parkinsonʼs disease. Molecules 2012; 17: 11391-11420
  • 15 Van Kampen JM, Baranowski DB, Shaw CA, Kay DG. Panax ginseng is neuroprotective in a novel progressive model of Parkinsonʼs disease. Exp Gerontol 2014; 50: 95-105
  • 16 González-Burgos E, Fernandez-Moriano C, Gómez-Serranillos MP. Potential neuroprotective activity of ginseng in Parkinsonʼs disease: a review. J Neuroimmune Pharmacol 2015; 10: 14-29
  • 17 Roodenrys S, Booth D, Bulzoma S, Phipps A, Micallef C, Smoker J. Chronic effects of Brahmi (Bacopa monnieri) on human memory. Neuropsychopharmacology 2002; 27: 279-281
  • 18 Stough C, Downey LA, Lloyd J, Silber B, Redman S, Hutchison C, Wesnes K, Nathan PJ. Examining the nootropic effects of a special extract of Bacopa monniera on human cognitive functioning: 90 day double-blind placebo-controlled randomized trial. Phytother Res 2008; 22: 1629-1634
  • 19 Barbhaiya HC, Desai RP, Saxena VS, Pravina K, Wasim P, Geetharani P, Allan JJ, Venkateshwarlu K, Amit A. Efficacy and tolerability of BacoMind® on memory improvement in elderly participants – a double blind placebo controlled study. Am J Pharmacol Toxicol 2008; 3: 425-434
  • 20 Dauer W, Przedborski S. Parkinsonʼs disease: mechanisms and models. Neuron 2003; 39: 889-909
  • 21 Yadav SK, Prakash J, Chouhan S, Westfall S, Verma M, Singh TD, Singh SP. Comparison of the neuroprotective potential of Mucuna pruriens seed extract with estrogen in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice model. Neurochem Int 2014; 65: 1-13
  • 22 Li XZ, Zhang SN, Liu SM, Lu F. Recent advances in herbal medicines treating Parkinsonʼs disease. Fitoterapia 2013; 84: 273-285
  • 23 Tavakkoli M, Miri R, Jassbi AR, Erfani N, Asadollahi M, Ghasemi M, Saso L, Firuzi O. Carthamus, Salvia and Stachys species protect neuronal cells against oxidative stress-induced apoptosis. Pharm Biol 2014; 52: 1550-1557
  • 24 Song JX, Sze SC, Ng TB, Lee CK, Leung GP, Shaw PC, Tong Y, Zhang YB. Anti-Parkinsonian drug discovery from herbal medicines: what have we got from neurotoxic models?. J Ethnopharmacol 2012; 139: 698-711
  • 25 More SV, Kumar H, Kang SM, Song SY, Lee K, Choi DK. Advances in neuroprotective ingredients of medicinal herbs by using cellular and animal models of Parkinsonʼs disease. Evid Based Complement Alternat Med 2013; 2013: 957875
  • 26 Solanki I, Parihar P, Mansuri ML, Parihar MS. Flavonoid-based therapies in the early management of neurodegenerative diseases. Adv Nutr 2015; 6: 64-72
  • 27 De Pedro N, Cantizani J, Ortiz-López FJ, González-Menéndez V, Cautain B, Rodríguez L, Bills GF, Reyes F, Genilloud O, Vicente F. Protective effects of isolecanoric acid on neurodegenerative in vitro models. Neuropharmacology 2015; 101: 538-548
  • 28 Lu XL, Lin YH, Wu Q, Su FJ, Ye CH, Shi L, He BX, Huang FW, Pei Z, Yao XL. Paeonolum protects against MPP+-induced neurotoxicity in zebrafish and PC12 cells. BMC Complement Altern Med 2015; 15: 137
  • 29 Coulom H, Birman S. Chronic exposure to rotenone models sporadic Parkinsonʼs disease in Drosophila melanogaster . J Neurosci 2004; 24: 10993-10998
  • 30 Strathearn KE, Yousef GG, Grace MH, Roy SL, Tambe MA, Ferruzzi MG, Wu QL, Simon JE, Lila MA, Rochet JC. Neuroprotective effects of anthocyanin- and proanthocyanidin-rich extracts in cellular models of Parkinsonʼs disease. Brain Res 2014; 1555: 60-77
  • 31 Sudati JH, Vieira FA, Pavin SS, Dias GR, Seeger RL, Golombieski R, Athayde ML, Soares FA, Rocha JB, Barbosa NV. Valeriana officinalis attenuates the rotenone-induced toxicity in Drosophila melanogaster . Neurotoxicology 2013; 37: 118-126
  • 32 Jansen RL, Brogan B, Whitworth AJ, Okello EJ. Effects of five Ayurvedic herbs on locomotor behaviour in a Drosophila melanogaster Parkinsonʼs disease model. Phytother Res 2014; 28: 1789-1795
  • 33 Kanazawa K, Sakakibara H. High content of dopamine, a strong antioxidant, in cavendish banana. J Agric Food Chem 2000; 48: 844-848
  • 34 Pereira A, Maraschin M. Banana (Musa spp) from peel to pulp: ethnopharmacology, source of bioactive compounds and its relevance for human health. J Ethnopharmacol 2015; 160: 149-163
  • 35 De Rus Jacquet A, Subedi R, Ghimire SK, Rochet JC. Nepalese traditional medicine and symptoms related to Parkinsonʼs disease and other disorders: Patterns of the usage of plant resources along the Himalayan altitudinal range. J Ethnopharmacol 2014; 153: 178-189
  • 36 Caruana M, Vassallo N. Tea polyphenols in Parkinsonʼs disease. Adv Exp Med Biol 2015; 863: 117-137
  • 37 Follmer C. Monoamine oxidase and α-synuclein as targets in Parkinsonʼs disease therapy. Expert Rev Neurother 2014; 14: 703-716
  • 38 Siddique YH, Jyoti S, Naz F. Effect of epicatechin gallate dietary supplementation on transgenic Drosophila model of Parkinsonʼs disease. J Diet Suppl 2014; 11: 121-130
  • 39 Li XZ, Zhang SN, Wang KX, Liu HY, Yang ZM, Liu SM, Lu F. Neuroprotective effects of extract of Acanthopanax senticosus harms on SH-SY5Y cells overexpressing wild-type or A53T mutant α-synuclein. Phytomedicine 2014; 21: 704-711
  • 40 Beppe GJ, Dongmo AB, Foyet HS, Tsabang N, Olteanu Z, Cioanca O, Hancianu M, Dimo T, Hritcu L. Memory-enhancing activities of the aqueous extract of Albizia adianthifolia leaves in the 6-hydroxydopamine-lesion rodent model of Parkinsonʼs disease. BMC Complement Altern Med 2014; 14: 142
  • 41 Berrocal R, Vasudevaraju P, Indi SS, Sambasiva Rao KR, Rao KS. In vitro evidence that an aqueous extract of Centella asiatica modulates α-synuclein aggregation dynamics. J Alzheimers Dis 2014; 39: 457-465
  • 42 Li H, Park G, Bae N, Kim J, Oh MS, Yang HO. Anti-apoptotic effect of modified Chunsimyeolda-tang, a traditional Korean herbal formula, on MPTP-induced neuronal cell death in a Parkinsonʼs disease mouse model. J Ethnopharmacol 2015; 176: 336-344
  • 43 Bae N, Chung S, Kim HJ, Cha JW, Oh H, Gu MY, Oh MS, Yang HO. Neuroprotective effect of modified Chungsimyeolda-tang, a traditional Korean herbal formula, via autophagy induction in models of Parkinsonʼs disease. J Ethnopharmacol 2015; 159: 93-101
  • 44 Purushothuman S, Nandasena C, Peoples CL, El Massri N, Johnstone DM, Mitrofanis J, Stone J. Saffron pre-treatment offers neuroprotection to nigral and retinal dopaminergic cells of MPTP-Treated mice. J Parkinsons Dis 2013; 3: 77-83
  • 45 Jahromi SR, Haddadi M, Shivanandappa T, Ramesh SR. Modulatory effect of Decalepis hamiltonii on ethanol-induced toxicity in transgenic Drosophila model of Parkinsonʼs disease. Neurochem Int 2015; 80: 1-6
  • 46 Guo H, Shi F, Li M, Liu Q, Yu B, Hu L. Neuroprotective effects of Eucommia ulmoides Oliv. and its bioactive constituent work via ameliorating the ubiquitin-proteasome system. BMC Complement Altern Med 2015; 15: 151
  • 47 Kwon SH, Ma SX, Hong SI, Kim SY, Lee SY, Jang CG. Eucommia ulmoides Oliv. bark attenuates 6-hydroxydopamine-induced neuronal cell death through inhibition of oxidative stress in SH-SY5Y cells. J Ethnopharmacol 2014; 152: 173-182
  • 48 Doo AR, Kim SN, Hahm DH, Yoo HH, Park JY, Lee H, Jeon S, Kim J, Park SU, Park HJ. Gastrodia elata Blume alleviates L-DOPA-induced dyskinesia by normalizing FosB and ERK activation in a 6-OHDA-lesioned Parkinsonʼs disease mouse model. BMC Complement Altern Med 2014; 14: 107
  • 49 Im AR, Kim YH, Uddin MR, Chae S, Lee HW, Kim YS, Lee MY. Neuroprotective effects of Lycium chinense Miller against rotenone-induced neurotoxicity in PC12 cells. Am J Chin Med 2013; 41: 1343-1359
  • 50 Siddique YH, Faisal M, Naz F, Jyoti S. Rahul. Role of Ocimum sanctum leaf extract on dietary supplementation in the transgenic Drosophila model of Parkinsonʼs disease. Chin J Nat Med 2014; 12: 777-781
  • 51 Khurana N, Gajbhiye A. Ameliorative effect of Sida cordifolia in rotenone induced oxidative stress model of Parkinsonʼs disease. Neurotoxicology 2013; 39: 57-64
  • 52 Gokul K. Muralidhara. Oral supplements of aqueous extract of tomato seeds alleviate motor abnormality, oxidative impairments and neurotoxicity induced by rotenone in mice: relevance to Parkinsonʼs disease. Neurochem Res 2014; 39: 1382-1394
  • 53 Kosaraju J, Chinni S, Roy PD, Kannan E, Antony AS, Kumar MN. Neuroprotective effect of Tinospora cordifolia ethanol extract on 6-hydroxy dopamine induced Parkinsonism. Indian J Pharmacol 2014; 46: 176-180
  • 54 Prakash J, Chouhan S, Yadav SK, Westfall S, Rai SN, Singh SP. Withania somnifera alleviates parkinsonian phenotypes by inhibiting apoptotic pathways in dopaminergic neurons. Neurochem Res 2014; 39: 2527-2536
  • 55 Nathan J, Panjwani S, Mohan V, Joshi V, Thakurdesai PA. Efficacy and safety of standardized extract of Trigonella foenum-graecum L. seeds as an adjuvant to L-Dopa in the management of patients with Parkinsonʼs disease. Phytother Res 2014; 28: 172-178
  • 56 Ryu HW, Oh WK, Jang IS, Park J. Amurensin G induces autophagy and attenuates cellular toxicities in a rotenone model of Parkinsonʼs disease. Biochem Biophys Res Commun 2013; 433: 121-126
  • 57 Fujimaki T, Saiki S, Tashiro E, Yamada D, Kitagawa M, Hattori N, Imoto M. Identification of licopyranocoumarin and glycyrurol from herbal medicines as neuroprotective compounds for Parkinsonʼs disease. PLoS One 2014; 9: e100395
  • 58 Budzianowski J. Tytoń – raz w zakładzie leczniczym. Czy zawiera substancje o właściwościach leczniczych? [Tobacco – once a medicinal plant. Does it contain substances with medicinal properties?]. Przegl Lek 2013; 70: 865-868
  • 59 Barreto GE, Iarkov A, Moran VE. Beneficial effects of nicotine, cotinine and its metabolites as potential agents for Parkinsonʼs disease. Front Aging Neurosci 2015; 6: 340
  • 60 Sun A, Xu X, Lin J, Cui X, Xu R. Neuroprotection by saponins. Phytother Res 2015; 29: 187-200
  • 61 Ahmed T, Gilani AU, Abdollahi M, Daglia M, Nabavi SF, Nabavi SM. Berberine and neurodegeneration: A review of literature. Pharmacol Rep 2015; 67: 970-979
  • 62 Wu CR, Tsai CW, Chang SW, Lin CY, Huang LC, Tsai CW. Carnosic acid protects against 6-hydroxydopamine-induced neurotoxicity in in vivo and in vitro model of Parkinsonʼs disease: involvement of antioxidative enzymes induction. Chem Biol Interact 2015; 225: 40-46
  • 63 Zhang Z, Li G, Szeto SS, Chong CM, Quan Q, Huang C, Cui W, Guo B, Wang Y, Han Y, Michael Siu KW, Yuen Lee SM, Chu IK. Examining the neuroprotective effects of protocatechuic acid and chrysin on in vitro and in vivo models of Parkinson disease. Free Radic Biol Med 2015; 84: 331-343
  • 64 Siddique YH, Jyoti S, Naz F. Effect of epicatechin gallate dietary supplementation on transgenic Drosophila model of Parkinsonʼs disease. J Diet Suppl 2014; 11: 121-130
  • 65 Tavassoly O, Kakish J, Nokhrin S, Dmitriev O, Lee JS. The use of nanopore analysis for discovering drugs which bind to α-synuclein for treatment of Parkinsonʼs disease. Eur J Med Chem 2014; 88: 42-54
  • 66 Antunes MS, Goes AT, Boeira SP, Prigol M, Jesse CR. Protective effect of hesperidin in a model of Parkinsonʼs disease induced by 6-hydroxydopamine in aged mice. Nutrition 2014; 30: 1415-1422
  • 67 Wu AG, Wong VK, Xu SW, Chan WK, Ng CI, Liu L, Law BY. Onjisaponin B derived from Radix Polygalae enhances autophagy and accelerates the degradation of mutant α-synuclein and huntingtin in PC-12 cells. Int J Mol Sci 2013; 14: 22618-22641
  • 68 Fredholm BB, Battig K, Holmén J, Nehlig A, Zvartau EE. Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol Rev 1999; 51: 83-133
  • 69 Ludwig IA, Clifford MN, Lean ME, Ashihara H, Crozier A. Coffee: biochemistry and potential impact on health. Food Funct 2014; 5: 1695-1717
  • 70 Qi H, Li S. Dose-response meta-analysis on coffee, tea and caffeine consumption with risk of Parkinsonʼs disease. Geriatr Gerontol Int 2014; 14: 430-439
  • 71 Gatto EM, Melcon C, Parisi VL, Bartoloni L, Gonzalez CD. Inverse association between yerba mate consumption and idiopathic Parkinsonʼs disease. A case-control study. J Neurol Sci 2015; 356: 163-167
  • 72 Pohanka M. The perspective of caffeine and caffeine derived compounds in therapy. Bratisl Med J 2015; 116: 520-530
  • 73 Ribeiro JA, Sebastião AM, de Mendonça A. Adenosine receptors in the nervous system: pathophysiological implications. Prog Neurobiol 2002; 68: 377-392
  • 74 Ribeiro JA, Sebastião AM, de Mendonça A. Participation of adenosine receptors in neuroprotection. Drug News Perspect 2003; 16: 80-86
  • 75 Fredholm BB, IJzerman AP, Jacobson KA, Linden J, Müller CE. International Union of Basic and Clinical Pharmacology. LXXXI. Nomenclature and classification of adenosine receptors – an update. Pharmacol Rev 2011; 63: 1-34
  • 76 Boison D. Adenosine as a neuromodulator in neurological diseases. Curr Opin Pharmacol 2008; 8: 2-7
  • 77 Pinna A, Wardas J, Simola N, Morelli M. New therapies for the treatment of Parkinsonʼs disease: adenosine A2A receptor antagonists. Life Sci 2005; 77: 3259-3267
  • 78 Sääksjärvi K, Knekt P, Rissanen H, Laaksonen MA, Reunanen A, Männistö S. Prospective study of coffee consumption and risk of Parkinsonʼs disease. Eur J Clin Nutr 2008; 62: 908-915
  • 79 Ascherio A, Zhang SM, Hernán MA, Kawachi I, Colditz GA, Speizer FE, Willett WC. Prospective study of caffeine consumption and risk of Parkinsonʼs disease in men and women. Ann Neurol 2001; 50: 56-63
  • 80 Chen JF, Chern Y. Impacts of methylxanthines and adenosine receptors on neurodegeneration: human and experimental studies. Handb Exp Pharmacol 2011; 200: 267-310
  • 81 Seidl SE, Potashkin JA. The promise of neuroprotective agents in Parkinsonʼs disease. Front Neurol 2011; 2: 68
  • 82 Chen JF, Xu K, Petzer JP, Staal R, Xu YH, Beilstein M, Sonsalla PK, Castagnoli K, Castagnoli N Jr. N, Schwarzschild MA. Neuroprotection by caffeine and A2A adenosine receptor inactivation in a model of Parkinsonʼs disease. J Neurosci 2001; 21: RC143
  • 83 Xu K, Xu YH, Chen JF, Schwarzschild MA. Caffeineʼs neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity shows no tolerance to chronic caffeine administration in mice. Neurosci Lett 2002; 322: 13-16
  • 84 Kalda A, Yu L, Oztas E, Chen JF. Novel neuroprotection by caffeine and adenosine A2A receptor antagonists in animal models of Parkinsonʼs disease. J Neurol Sci 2006; 248: 9-15
  • 85 Morelli M, Wardas J. Adenosine A2a receptor antagonists: potential therapeutic and neuroprotective effects in Parkinsonʼs disease. Neurotox Res 2008; 3: 545-556
  • 86 Xu K, Xu YH, Chen JF, Schwarzschild MA. Neuroprotection by caffeine: time course and role of its metabolites in the MPTP model of Parkinsonʼs disease. Neuroscience 2010; 167: 475-481
  • 87 Postuma RB, Lang AE, Munhoz RP, Charland K, Pelletier A, Moscovich M, Filla L, Zanatta D, Rios Romenets S, Altman R, Chuang R, Shah B. Caffeine for treatment of Parkinson disease. A randomized controlled trial. Neurology 2012; 79: 651-658
  • 88 ClinicalTrials.gov. Caffeine for motor manifestations of Parkinsonʼs disease. Available at. https://www.clinicaltrials.gov/ct2/show/study/NCT01190735 Accessed January 21, 2016
  • 89 ClinicalTrials.gov. Caffeine as a therapy for Parkinsonʼs disease. Available at. https://www.clinicaltrials.gov/ct2/show/NCT01738178 Accessed January 21, 2016
  • 90 Petzer JP, Castagnoli N, Schwarzschild MA, Chen JF, Van der Schyf CJ. Dual-target-directed drugs that block monoamine oxidase B and adenosine A2A receptors for Parkinsonʼs disease. Neurotherapeutics 2009; 6: 141-151
  • 91 Petzer JP, Petzer A. Caffeine as a lead compound for the design of therapeutic agents for the treatment of Parkinsonʼs disease. Curr Med Chem 2015; 22: 975-988
  • 92 Shoulson I, Chase T. Caffeine and the antiparkinsonian response to levodopa or piribedil. Neurology 1975; 25: 722-724
  • 93 Kartzinel R, Shoulson I, Calne DB. Studies with bromocriptine: III. Concomitant administration of caffeine to patients with idiopathic parkinsonism. Neurology 1976; 26: 741-743