Phytotherapeutic approaches in Parkinson’s disease: Bioactive compounds, neuroprotective mechanisms, and clinical perspectives
DOI:
https://doi.org/10.14719/gst.e4Keywords:
Alpha-synuclein, medicinal plants, neurological disorder, Parkinson's disease, pathophysiology, phytochemicalsAbstract
Parkinson’s disease and other neurological disorders are a significant public health concern, with nearly a billion people globally suffering from them. It is a progressive neurodegenerative disorder characterised by the loss of dopaminergic neurons, leading to motor and cognitive dysfunction. Current therapies relieve symptoms but do not efficiently halt disease progression and may have deleterious effects in the long term. Consequently, there has been growing interest in using medicinal plants and their bioactive phytochemicals (such as polyphenols, terpenes, and alkaloids) as possible neuroprotectants. Preclinical studies have shown that these compounds modulate dopaminergic signalling, reduce oxidative stress and neuroinflammation, improve mitochondrial function and regulate metal ion homeostasis. However, most evidence is derived from preventive studies using toxin-induced models such as MPTP (1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine), 6-hydroxydopamine (6-OHDA), and rotenone, which only partially reproduce the progressive and multifactorial pathology of idiopathic human Parkinson’s Disease. Moreover, clear evidence for disease-modifying efficacy in long-term clinical investigations remains lacking. This review provides an updated synthesis of medicinal plants, phytochemicals, neuroprotective mechanisms, and growing clinical evidence while addressing obstacles relating to standardisation, safety, regulatory considerations, and translational reliability. It also outlines major knowledge gaps and future research goals to assist the clinical incorporation of evidence-based phytotherapeutic therapies for Parkinson's disease.
References
1. Klein C, Westenberger A. Genetics of Parkinson's disease. Cold Spring Harb Perspect Med. 2012;2(1):a008888. doi:10.1101/cshperspect.a008888.
2. Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W, et al. MDS clinical diagnostic criteria for Parkinson's disease. Mov Disord. 2015;30(12):1591-601. doi:10.1002/mds.26424.
3. GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392(10159):1789-1858. doi:10.1016/S0140-6736(18)32279-7.
4. GBD 2016 Parkinson's Disease Collaborators. Global, regional, and national burden of Parkinson's disease, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2018;17(11):939-953. doi:10.1016/S1474-4422(18)30295-3.
5. Luo Y, Qiao L, Li M, Wen X, Zhang W, Li X. Global, regional, national epidemiology and trends of Parkinson's disease from 1990 to 2021: findings from the Global Burden of Disease Study 2021. Front Aging Neurosci. 2024;16:1498756. doi:10.3389/fnagi.2024.1498756.
6. Rahman MM, Wang X, Islam MR, Akash S, Supti FA, Mitu MI, et al. Multifunctional role of natural products for the treatment of Parkinson's disease: at a glance. Front Pharmacol. 2022;13:976385. doi:10.3389/fphar.2022.976385.
7. Fox SH, Katzenschlager R, Lim SY, Barton B, de Bie RMA, Seppi K, et al. International Parkinson and Movement Disorder Society evidence-based medicine review: update on treatments for the motor symptoms of Parkinson's disease. Mov Disord. 2018;33(8):1248-1266. doi:10.1002/mds.27372.
8. Kostelnik A, Cegan A, Pohanka M. Anti-Parkinson drug biperiden inhibits enzyme acetylcholinesterase. Biomed Res Int. 2017;2017:2532764. doi:10.1155/2017/2532764.
9. Amro MS, Teoh SL, Norzana AG, Srijit D. The potential role of herbal products in the treatment of Parkinson's disease. Clin Ter. 2018;169(1):23-33. doi:10.7417/T.2018.2050.
10. Luo S, Zhang L, Wu X, Wang J, Li Q, Chen W, et al. Therapeutic potential of neuroprotective plant extracts in Parkinson's disease. Front Neurosci. 2026;20:1813133. doi:10.3389/fnins.2026.1813133.
11. Akhondzadeh S, Abbasi SH. Herbal medicine in the treatment of Alzheimer's disease. Am J Alzheimers Dis Other Demen. 2006;21(2):113-18. doi:10.1177/153331750602100211.
12. Lundstrom K, Pham HT, Dinh LD. Interaction of plant extracts with central nervous system receptors. Medicines. 2017;4(1):12. doi:10.3390/medicines4010012.
13. Kale MB, Bajaj K, Umare M, Wankhede NL, Taksande BG, Umekar MJ, et al. Exercise and nutraceuticals: eminent approach for diabetic neuropathy. Curr Mol Pharmacol. 2022;15(1):108-28. doi:10.2174/1874467214666210629123010.
14. Khazdair MR, Kianmehr M, Anaeigoudari A. Effects of medicinal plants and flavonoids on Parkinson's disease: a review on basic and clinical evidence. Adv Pharm Bull. 2021;11(2):224-32. doi:10.34172/apb.2021.026.
15. Dagra A, Miller DR, Lin M, Gopinath A, Shaerzadeh F, Harris S, et al. α-Synuclein-induced dysregulation of neuronal activity contributes to murine dopamine neuron vulnerability. NPJ Parkinsons Dis. 2021;7(1):76. doi:10.1038/s41531-021-00210-w.
16. Srinivasan E, Chandrasekhar G, Chandrasekar P, Anbarasu K, Vickram AS, Karunakaran R, et al. Alpha-synuclein aggregation in Parkinson's disease. Front Med. 2021;8:736978. doi:10.3389/fmed.2021.736978.
17. Chaudhuri KR, Healy DG, Schapira AH. Non-motor symptoms of Parkinson's disease: diagnosis and management. Lancet Neurol. 2006;5(3):235-45. doi:10.1016/S1474-4422(06)70373-8.
18. Schapira AHV, Chaudhuri KR, Jenner P. Non-motor features of Parkinson disease. Nat Rev Neurosci. 2017;18(7):435-50. doi:10.1038/nrn.2017.62.
19. Sveinbjornsdottir S. The clinical symptoms of Parkinson's disease. J Neurochem. 2016;139(Suppl 1):318-24. doi:10.1111/jnc.13691.
20. Poewe W, Seppi K, Tanner CM, Halliday GM, Brundin P, Volkmann J, et al. Parkinson disease. Nat Rev Dis Primers. 2017;3:17013. doi:10.1038/nrdp.2017.13.
21. Sukmueng N, Phokaewvarangkul O, Bhidayasiri R. Plant-derived therapies in Parkinson's disease: a systematic review of clinical evidence. J Neural Transm (Vienna). 2026 Jul 23. doi:10.1007/s00702-026-03239-4.
22. Firenzuoli F, Gori L. Herbal medicine today: clinical and research issues. Evid Based Complement Alternat Med. 2007;4(Suppl 1):37-40. doi:10.1093/ecam/nem096.
23. Jankovic J, Poewe W. Therapies in Parkinson's disease. Curr Opin Neurol. 2012;25(4):433-47. doi:10.1097/WCO.0b013e3283542fc2.
24. Yan L, Guo MS, Zhang Y, Yu L, Wu JM, Tang Y, et al. Dietary plant polyphenols as the potential drugs in neurodegenerative diseases: current evidence, advances, and opportunities. Oxid Med Cell Longev. 2022;2022:5288698. doi:10.1155/2022/5288698.
25. Ayaz M, Ali T, Sadiq A, Ullah F, Naseer MI. Editorial: current trends in medicinal plant research and neurodegenerative disorders. Front Pharmacol. 2022;13:922373. doi:10.3389/fphar.2022.922373.
26. So YJ, Lee JU, Yang GS, Yang G, Kim SW, Lee JH, et al. The potentiality of natural products and herbal medicine as novel medications for Parkinson's disease: a promising therapeutic approach. Int J Mol Sci. 2024;25(2):1071. doi:10.3390/ijms25021071.
27. Saraswathi S, Venkataravanappa JT, Nambiar C, Saji S, Kori V, Murthy MN, et al. Plant-derived neuroprotective compounds and nanoformulations targeting Parkinson's disease: a semi-systematic review of mechanisms and therapeutic potential. Metab Brain Dis. 2026;41(1):101. doi:10.1007/s11011-026-01868-y.
28. Kumari N, Anand S, Shah K, Chauhan NS, Sethiya NK, Singhal M. Emerging role of plant-based bioactive compounds as therapeutics in Parkinson's disease. Molecules. 2023;28(22):7588. doi:10.3390/molecules28227588.
29. Mandal M, Jaiswal P, Mishra A. Role of curcumin and its nanoformulations in neurotherapeutics: a comprehensive review. J Biochem Mol Toxicol. 2020;34(6):e22478. doi:10.1002/jbt.22478.
30. Xia S, Fang D. Pharmacological action and mechanisms of ginkgolide B. Chin Med J. 2007;120(10):922-28.
31. Katzenschlager R, Evans A, Manson A, Palsalos PN, Ratnaraj N, Watt H, et al. Mucuna pruriens in Parkinson's disease: a double-blind clinical and pharmacological study. J Neurol Neurosurg Psychiatry. 2004;75:1672-77. doi:10.1136/jnnp.2003.028761.
32. Dos Santos MG, Schimith LE, André-Miral C, Muccillo-Baisch AL, Arbo BD, Hort MA. Neuroprotective effects of resveratrol in in vivo and in vitro experimental models of Parkinson's disease: a systematic review. Neurotox Res. 2022;40(1):319-45. doi:10.1007/s12640-021-00450-x.
33. Mirza FJ, Zahid S, Holsinger RMD. Neuroprotective effects of carnosic acid: insight into its mechanisms of action. Molecules. 2023;28(5):2306. doi:10.3390/molecules28052306.
34. Prakash J, Yadav SK, Chouhan S, Singh SP. Neuroprotective role of Withania somnifera root extract in maneb-paraquat induced mouse model of parkinsonism. Neurochem Res. 2013;38(5):972-80. doi:10.1007/s11064-013-1005-4.
35. Kulkarni SK, Dhir A. Withania somnifera: an Indian ginseng. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(5):1093-105. doi:10.1016/j.pnpbp.2007.09.011.
36. Ahmad B, Rehman MU, Amin I, Arif A, Rasool S, Bhat SA, et al. A review on pharmacological properties of zingerone (4-(4-hydroxy-3-methoxyphenyl)-2-butanone). Sci World J. 2015;2015:816364. doi:10.1155/2015/816364.
37. Singh A, Tripathi P, Yadawa AK, Singh S. Promising polyphenols in Parkinson's disease therapeutics. Neurochem Res. 2020;45(8):1731-45. doi:10.1007/s11064-020-03058-3.
38. Niu C, Zou Y, Dong M, Niu Y. Plant-derived compounds as potential neuroprotective agents in Parkinson's disease. Nutrition. 2025;130:112610. doi:10.1016/j.nut.2024.112610.
39. Duan WJ, Liang L, Pan MH, Lu DH, Wang TM, Li SB, et al. Theacrine, a purine alkaloid from Kucha, protects against Parkinson's disease through SIRT3 activation. Phytomedicine. 2020;77:153281. doi:10.1016/j.phymed.2020.153281.
40. Fu R, Wang Y, Chen C, Tsai R, Liu S, Chang W, et al. Acetylcorynoline attenuates dopaminergic neuron degeneration and α-synuclein aggregation in animal models of Parkinson's disease. Neuropharmacology. 2014;82:108-120. doi:10.1016/j.neuropharm.2013.08.007.
41. Baccouri B, Rajhi I. Potential antioxidant activity of terpenes. In: Terpenes and terpenoids-recent advances. 2021. doi:10.5772/intechopen.96638.
42. Aijaz M, Kumar A, Ahmad M, Ansari MA. Plant-based therapies in Parkinson's disease management: mechanisms, clinical evidence, and future perspectives. Lett Appl NanoBiosci. 2024;13(3):148. doi:10.33263/LIANBS133.148.
43. Iwasaki K, Kato S, Monma Y, Niu K, Ohrui T, Okitsu R, et al. A pilot study of Banxia Houpu Tang, a traditional Chinese medicine, for reducing pneumonia risk in older adults with dementia. J Am Geriatr Soc. 2007;55(12):2035-40. doi:10.1111/j.1532-5415.2007.01448.x.
44. Kim DW, Kwon HW, Kim SH. Efficacy and safety of Banxia-Houpo-Tang (Banha-Hubak-Tang) for depression: a systematic review and meta-analysis. Complement Ther Clin Pract. 2023;52:101769. doi:10.1016/j.ctcp.2023.101769.
45. Iwasaki K, Wang Q, Seki H, Satoh K, Takeda A, Arai H, et al. The effects of the traditional Chinese medicine “Banxia Houpo Tang (Hange-Koboku To)” on the swallowing reflex in Parkinson's disease. Phytomedicine. 2000;7(4):259-63. doi:10.1016/S0944-7113(00)80042-2.
46. Zhou Y, Wang DG, Lu ZY, et al. Clinical trial of Bushen Yanggan Xifeng decoction on Parkinson disease with liver and kidney Yin deficiency. Liaoning J Tradit Chin Med. 2013;40:929-931. doi:10.12032/aging20200923016.
47. Shu D, He J, Chen J. Neuroprotective effects and mechanisms of Chuanxiong Chatiao pulvis against MPTP-induced dopaminergic neurotoxicity in mice model of Parkinson's disease. Zhongguo Zhong Yao Za Zhi. 2009;34(19):2494-97.
48. Jin J, Duan L, Sun J. Protective effect of Huanglian Jiedu decoction on the injury of PC12 cells induced by MPP+. Chin Pharm J. 2008;43(5):344-48.
49. Zhou SF, Qian HY. Effects of Liuwei Dihuang Pill on dopaminergic neurons in MPTP-induced PD mice. Hubei J Tradit Chin Med. 2009;31:6-7.
50. Lo YC, Shih YT, Tseng YT, Hsu HT. Neuroprotective effects of San-Huang-Xie-Xin-Tang in the MPP+/MPTP models of Parkinson's disease in vitro and in vivo. Evid Based Complement Alternat Med. 2012;2012:501032. doi:10.1155/2012/501032.
51. Wang WW, He JC, Ding HJ. Effect of Tianma Gouteng drink on the behavioural and oxidative stress response of Parkinson's disease rats. J Gerontol. 2010;30:1657-59.
52. Li XM, Xu CL, Deng JM, Li LF, Ma SP, Qu R. Protective effect of Zhen-Wu-Tang through keeping DA stable and VMAT2/DAT mRNA in balance in rats with striatal lesions induced by MPTP. J Ethnopharmacol. 2011;134(3):768-74. doi:10.1016/j.jep.2011.01.040.
53. Wentao L, Huifen S, Wang Y, Rukui L, Yi L, Lu Y. Effect of Zhichan Decoction on neural stem cell differentiation in Parkinson's disease model rats. World Sci Technol. 2011;13(3):475-79. doi:10.1016/S1876-3553(12)60011-8.
54. Zhang J, Zhang Z, Zhang W, Li X, Wu T, Li T, et al. Jia-Jian-Di-Huang-Yin-Zi decoction exerts neuroprotective effects on dopaminergic neurons and their microenvironment. Sci Rep. 2018;8(1):9886. doi:10.1038/s41598-018-27852-w.
55. Liu C, Huang X, Qiu S, Chen W, Li W, Zhang H, et al. Chinese herbal complex “Bu Shen Jie Du Fang” modulated autophagy in an MPP+-induced cell model of Parkinson's disease. Evid Based Complement Alternat Med. 2019;2019:8920813. doi:10.1155/2019/8920813.
56. Chen C, Zhang BB, Hu AL, Li H, Liu J, Zhang F. Protective role of cinnabar and realgar in Hua-Feng-Dan against LPS plus rotenone-induced neurotoxicity and disturbance of gut microbiota in rats. J Ethnopharmacol. 2020;247:112299. doi:10.1016/j.jep.2019.112299.
57. Eid Abdelmagyd HA, Ram Shetty DS, Musa Musleh Al-Ahmari DM. Herbal medicine as adjunct in periodontal therapies: a review of clinical trials in past decade. J Oral Biol Craniofac Res. 2019;9(3):212-17. doi:10.1016/j.jobcr.2019.05.001.
58. Baragi U, Baragi P, Vyas M, Shukla V. Standardization and quality control parameters of Dashanga Kwatha Ghana tablet: an Ayurvedic formulation. Int J Ayurveda Res. 2011;2:42-47. doi:10.4103/0974-7788.83190.
59. Khanam S, Subitsha AJ, Sabu S. Plants as a promising source for the treatment of Parkinson disease: a systematic review. IP Int J Compr Adv Pharmacol. 2020;5(4):158-66. doi:10.18231/j.ijcaap.2020.032.
60. Gopalakrishna PK, Karikalan B, Rao VT, Naik VR, Sura S, Jagadeesan S, et al. Medicinal plants: a promising approach for the treatment of Parkinson's disease. Int J Appl Eng Technol. 2024;6(1):1292-1306.
61. Marzouk MM, Farid MM, Hegazi NM, Ezzat SM. Drug discovery from medicinal plants against Alzheimer's disease. In: Phytochemistry in drug discovery for central nervous system disorders. 2023. p. 43-80. doi:10.1002/9781119794127.ch3.
62. Emanuel EJ, Miller FG. The ethics of placebo-controlled trials: a middle ground. N Engl J Med. 2001;345:915-19.
63. Kim TH, Cho KH, Jung WS, Lee MS. Herbal medicines for Parkinson's disease: a systematic review of randomized controlled trials. PLoS One. 2012;7:e35695. doi:10.1371/journal.pone.0035695.
64. Ghodsi H, Rahimi HR, Aghili SM, Saberi A, Ghodsi A, Shoeibi A. Evaluation of curcumin as add-on therapy in patients with Parkinson's disease: a pilot randomized, triple-blind, placebo-controlled trial. Clin Neurol Neurosurg. 2022;218:107300. doi:10.1016/j.clineuro.2022.107300.
65. Postuma RB, Anang J, Pelletier A, Joseph L, Moscovich M, Grimes D, et al. Caffeine as symptomatic treatment for Parkinson disease (Café-PD): a randomized trial. Neurology. 2017;89(17):1795-1803. doi:10.1212/WNL.0000000000004568.
66. Sengupta T, Vinayagam J, Singh R, Jaisankar P, Mohanakumar KP. Plant-derived natural products for Parkinson's disease therapy. Adv Neurobiol. 2016;12:415-496. doi:10.1007/978-3-319-28383-8_23.
67. Schneider F, Erisson L, Beygi H, Bradbury M, Cohen-Barak O, Grachev ID, et al. Pharmacokinetics, metabolism and safety of deuterated L-DOPA (SD-1077)/carbidopa compared to L-DOPA/carbidopa following single oral dose administration in healthy subjects. Br J Clin Pharmacol. 2018;84(10):2422-32. doi:10.1111/bcp.13702.
68. Fu PP, Chiang HM, Xia Q, Chen T, Chen BH, Yin JJ, et al. Quality assurance and safety of herbal dietary supplements. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2009;27:91-119. doi:10.1080/10590500902885676.
69. Müller T. The safety of istradefylline for the treatment of Parkinson's disease. Expert Opin Drug Saf. 2015;14(5):769-75. doi:10.1517/14740338.2015.1014798.
70. Nafiu MO, Hamid AA, Muritala HF, Adeyemi SB. Preparation, standardization, and quality control of medicinal plants in Africa. In: Medicinal spices and vegetables from Africa: therapeutic potential against metabolic, inflammatory, infectious and systemic diseases. 2017. p. 171-204. doi:10.1016/B978-0-12-809286-6.00007-8.
71. See WZC, Naidu R, Tang KS. Cellular and molecular events leading to paraquat-induced apoptosis: mechanistic insights into Parkinson's disease pathophysiology. Mol Neurobiol. 2022;59(6):3353-69. doi:10.1007/s12035-022-02799-2.
72. Yang Y, Zhang Z, Li S, Ye X, Li X, He K. Synergy effects of herb extracts: pharmacokinetics and pharmacodynamic basis. Fitoterapia. 2014;92:133-47. doi:10.1016/j.fitote.2013.10.010.
73. Schneider SA, Alcalay RN. Precision medicine in Parkinson's disease: emerging treatments for genetic Parkinson's disease. J Neurol. 2020;267(3):860-69. doi:10.1007/s00415-020-09705-7.
74. Calderón-Larrañaga A, Vetrano DL, Ferrucci L, Mercer SW, Marengoni A, Onder G, et al. Multimorbidity and functional impairment: bidirectional interplay, synergistic effects and common pathways. J Intern Med. 2019;285:255-71. doi:10.1111/joim.12843.
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