Neuroprotective Changes Induced In Substantia Nigra Of Rats By The Combination Of Passiflora, Melatonin & Vitamin B6
DOI:
https://doi.org/10.36283/ziun-pjmd15-1/002Keywords:
Alpha-Synuclein, Melatonin, Vitamin B6, PassifloraAbstract
Background: Parkinson's is an age-related neurodegenerative disorder characterized by loss of dopaminergic neurons. The standard drug Levodopa has been used in the treatment of Parkinson’s for decades, but long-term use leads to motor complications like dyskinesia and on-off phenomena. This study aimed to observe the neuroprotective effect of supplements (melatonin, vitamin B6, and Passiflora) in a rat model.
Method: This was an experimental animal study conducted on healthy male albino Wistar rats weighing between 150-200 g. The study was conducted at Baqai Medical University and Dow University of Health Sciences after getting approval from IREB of BMU (BMU-IREB/03-2023) for a period of 6 months. The Model was formed by MPTP (1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine). 40 rats were selected by using the power analysis technique & were divided into groups: A: Control, 0.9% saline, B: MPTP, C: MPTP + Levodopa, D: MPTP + Levodopa + Supplement (melatonin 10mg/kg, Passiflora 25mg/kg & vitamin B6 100mg/kg). Weight of animals & behaviour tests (Pole and Plus Maze) were recorded for 5 weeks. Brains were isolated to observe histological changes & Alpha synuclein expression. Data was analysed by using SPSS version 27. One-way analysis of variance (ANOVA) was applied followed by an independent sample t-test.
Results: Behavioural analysis revealed a statistically significant difference between MPTP and treatment groups (p<0.001). Bradykinesia was reduced after the intake of the supplement in the pole test. The time spent in the open arm of the plus maze was significantly improved by approximately 80.28% (p<0.001) with supplement + L-Dopa. MPTP caused 50% reduction in the neuronal count, observed on H&E staining, while the supplement ameliorated this decrease. Degenerative changes like pyknosis, shrinkage, glial infiltration, and vacuolation were improved in the levodopa + supplement group(p<0.001). IHC revealed, supplement reduced the accumulation of alpha synuclein aggregates, which were around 25-30-fold in the MPTP group.
Conclusion: The supplement has a neuroprotective role as observed by betterment in behavioural performance, improvement in neuronal degeneration, and reduction in the expression of alpha synuclein.
References
1. Tolosa E, Garrido A, Scholz SW, Poewe W. Challenges in the diagnosis of Parkinson's disease. The Lancet Neurology. 2021 May 1;20(5):385-97. DOI: 10.1016/S1474-4422(21)00030-2
2. Jankovic J, Tan EK. Parkinson’s disease: Etiopathogenesis and treatment. Journal of Neurology, Neurosurgery & Psychiatry. 2020 Aug 1;91(8):795-808. DOI: 10.1136/jnnp-2019-322338
3. Srinivasan E, Chandrasekhar G, Chandrasekar P, Anbarasu K, Vickram AS, Karunakaran R, Rajasekaran R, Srikumar PS. Alpha-synuclein aggregation in Parkinson's disease. Frontiers in medicine. 2021 Oct 18;8:736978. DOI: 10.3389/fmed.2021.736978
4. Murakami H, Shiraishi T, Umehara T, Omoto S, Iguchi Y. Recent advances in drug therapy for parkinson's disease. Internal Medicine. 2023 Jan 1;62(1):33-42. DOI: 10.2169/internalmedicine.8940-21
5. Rojo-Sebastián A, González-Robles C, de Yébenes JG. Vitamin B6 deficiency in patients with Parkinson disease treated with levodopa/carbidopa. Clinical Neuropharmacology. 2020 Sep 1;43(5):151-7. DOI: 10.1097/WNF.0000000000000408
6. Brandão LE, Nôga DA, Dierschnabel AL, Campêlo CL, Meurer YD, Lima RH, Engelberth RC, Cavalcante JS, Lima CA, Marchioro M, Estevam CD. Passiflora cincinnata extract delays the development of motor signs and prevents dopaminergic loss in a mice model of parkinson’s disease. Evidence-Based Complementary and Alternative Medicine. 2017 Aug 1;2017. DOI:10.1155/2017/8429290
7. Naskar A, Prabhakar V, Singh R, Dutta D, Mohanakumar KP. Melatonin enhances L‐DOPA therapeutic effects, helps to reduce its dose, and protects dopaminergic neurons in 1‐methyl‐4‐phenyl‐1, 2, 3, 6‐tetrahydropyridine‐induced Parkinsonism in mice. Journal of pineal research. 2015 Apr;58(3):262-74. DOI: 10.1111/jpi.12212
8. Lin CH, Wei PC, Chen CM, Huang YT, Lin JL, Lo YS, Lin JL, Lin CY, Wu YR, Chang KH, Lee-Chen GJ. Lactulose and melibiose attenuate MPTP-induced Parkinson’s disease in mice by inhibition of oxidative stress, reduction of neuroinflammation and up-regulation of autophagy. Frontiers in Aging Neuroscience. 2020 Jul 24;12:226. DOI: 10.3389/fnagi.2020.00226
9. El-Shamarka ME, Kozman MR, Messiha BA. The protective effect of inosine against rotenone-induced Parkinson’s disease in mice; role of oxido-nitrosative stress, ERK phosphorylation, and A2AR expression. Naunyn-schmiedeberg's Archives of Pharmacology. 2020 Jun;393:1041-53. DOI: 10.1007/s00210-019-01804-1
10. Olofinnade AT, Onaolapo TM, Oladimeji S, Fatoki AM, Balogun CI, Onaolapo AY, Onaolapo OJ. An evaluation of the effects of pyridoxal phosphate in chlorpromazine-induced parkinsonism using mice. Central Nervous System Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Central Nervous System Agents). 2020 Apr 1;20(1):13-25. DOI: 10.2174/1871524920666200120142508
11. Ma Y, Rong Q. Effect of different MPTP administration intervals on mouse models of Parkinson’s disease. Contrast media & molecular imaging. 2022;2022(1):2112146. DOI: 10.1155/2022/2112146
12. Wada M, Ang MJ, Weerasinghe-Mudiyanselage PD, Kim SH, Kim JC, Shin T, Moon C. Behavioral characterization in MPTP/p mouse model of Parkinson’s disease. Journal of Integrative Neuroscience. 2021 Jun 30;20(2):307-20. DOI: 10.31083/j.jin2002030
13. Kacprzyk KW, Milewska M, Zarnowska A, Panczyk M, Rokicka G, Szostak-Wegierek D. Prevalence of malnutrition in patients with Parkinson’s disease: a systematic review. Nutrients. 2022 Dec 6;14(23):5194. DOI: 10.3390/nu14235194
14. Zheng R, Ruan Y, Yan Y, Lin Z, Xue N, Yan Y, Tian J, Yin X, Pu J, Zhang B. Melatonin attenuates neuroinflammation by down-regulating NLRP3 inflammasome via a SIRT1-dependent pathway in MPTP-induced models of Parkinson’s disease. Journal of Inflammation Research. 2021 Jul 8:3063-75. DOI: 10.2147/JIR.S317672
15. Wei Y, Lu M, Mei M, Wang H, Han Z, Chen M, Yao H, Song N, Ding X, Ding J, Xiao M. Pyridoxine induces glutathione synthesis via PKM2-mediated Nrf2 transactivation and confers neuroprotection. Nature communications. 2020 Feb 18;11(1):941. DOI: 10.1038/s41467-020-14788-x
16. Kim GH, Yi SS. Chronic oral administration of Passiflora incarnata extract has no abnormal effects on metabolic and behavioral parameters in mice, except to induce sleep. Laboratory Animal Research. 2019 Dec;35:1-8. DOI: 10.1186/s42826-019-0034-9
17. Özkan A, Bülbül M, Derin N, Sinen O, Akçay G, Parlak H, ASLAN MA, Ağar A. Neuropeptide-S affects cognitive impairment and depression-like behavior on MPTPinduced experimental mouse model of Parkinson? s disease. Turkish Journal of Medical Sciences. 2021;51(6):3126-35. DOI: 10.3906/sag-2105-74
18. Li J, Liu H, Wang X, Xia Y, Huang J, Wang T, Lin Z, Xiong N. Melatonin ameliorates Parkinson’s disease via regulating microglia polarization in a RORα‐dependent pathway. npj Parkinson's Disease. 2022 Jul 8;8(1):90. DOI: 10.1038/s41531-022-00352-5
19. Sherzai AZ, Tagliati M, Park K, Pezeshkian S, Sherzai D. Micronutrients and risk of Parkinson’s disease: a systematic review. Gerontology and geriatric medicine. 2016 Apr 20;2:2333721416644286. DOI: 10.1177/2333721416644286
20. Murakami K, Miyake Y, Sasaki S, Tanaka K, Fukushima W, Kiyohara C, Tsuboi Y, Yamada T, Oeda T, Miki T, Kawamura N. Dietary intake of folate, vitamin B6, vitamin B12 and riboflavin and risk of Parkinson's disease: a case–control study in Japan. British Journal of Nutrition. 2010 Sep;104(5):757-64. DOI: 10.1017/S0007114510001005
21. Tzoneva R, Georgieva I, Ivanova N, Uzunova V, Nenchovska Z, Apostolova S, Stoyanova T, Tchekalarova J. The role of melatonin on behavioral changes and concomitant oxidative stress in icvAβ1-42 rat model with pinealectomy. International Journal of Molecular Sciences. 2021 Nov 25;22(23):12763. DOI: 10.3390/ijms222312763
22. Field DT, Cracknell RO, Eastwood JR, Scarfe P, Williams CM, Zheng Y, Tavassoli T. High‐dose Vitamin B6 supplementation reduces anxiety and strengthens visual surround suppression. Human Psychopharmacology: Clinical and Experimental. 2022 Nov;37(6):e2852. DOI: 10.1002/hup.2852
23. Amini F, Amini-Khoei H, Haratizadeh S, Setayesh M, Basiri M, Raeiszadeh M, Nozari M. Hydroalcoholic extract of Passiflora incarnata improves the autistic-like behavior and neuronal damage in a valproic acid-induced rat model of autism. Journal of Traditional and Complementary Medicine. 2023 Jul 1;13(4):315-24. DOI: 10.1016/j.jtcme.2023.02.005
24. Asemi-Rad A, Moafi M, Aliaghaei A, Abbaszadeh HA, Abdollahifar MA, Ebrahimi MJ, Heidari MH, Sadeghi Y. The effect of dopaminergic neuron transplantation and melatonin co- administration on oxidative stress-induced cell death in Parkinson’s disease. Metabolic Brain Disease. 2022 Dec;37(8):2677-85. DOI: 10.1007/s11011-022-01021-5
25. Eltony SA. Histological study on the protective role of vitamin B complex on the cerebellum of diabetic rat. Tissue and Cell. 2016 Aug 1;48(4):283-96. DOI: 10.1016/j.tice.2016.06.009
26. Kim GH, Lim K, Yang HS, Lee JK, Kim Y, Park SK, Kim SH, Park S, Kim TH, Moon JS, Hwang IK. Improvement in neurogenesis and memory function by administration of Passiflora incarnata L. extract applied to sleep disorder in rodent models. Journal of Chemical Neuroanatomy. 2019 Jul 1;98:27-40. DOI: 10.1016/j.jchemneu.2019.03.005
27. Mazumder S, Bahar AY, Shepherd CE, Prasad AA. Post-mortem brain histological examination in the substantia nigra and subthalamic nucleus in Parkinson’s disease following deep brain stimulation. Frontiers in Neuroscience. 2022 Sep 14;16:948523. DOI: 10.3389/fnins.2022.948523
28. Reyes JF, Ekmark-Léwen S, Perdiki M, Klingstedt T, Hoffmann A, Wiechec E, Nilsson P, Nilsson KP, Alafuzoff I, Ingelsson M, Hallbeck M. Accumulation of alpha-synuclein within the liver, potential role in the clearance of brain pathology associated with Parkinson’s disease. Acta neuropathologica communications. 2021 Dec;9:1-20. DOI: 10.1186/s40478-021-01136-3
29. Jia H, Liu Z, Li X, Feng Z, Hao J, Li X, Shen W, Zhang H, Liu J. Synergistic anti-Parkinsonism activity of high doses of B vitamins in a chronic cellular model. Neurobiology of aging. 2010 Apr 1;31(4):636-46. DOI: 10.1016/j.neurobiolaging.2008.05.031
30. Muhammad F, Liu Y, Wang N, Zhao L, Zhou Y, Yang H, Li H. Anti-α-Synuclein toxicity and anti-neurodegenerative role of chrysin in transgenic Caenorhabditis elegans models of Parkinson’s disease. ACS Chemical Neuroscience. 2022 Feb 4;13(4):442-53. DOI: 10.1021/acschemneuro.1c00548
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Pakistan Journal of Medicine and Dentistry
This work is licensed under a Creative Commons Attribution 4.0 International License.
This is an open-access article distributed under the terms of the CreativeCommons Attribution License (CC BY) 4.0 https://creativecommons.org/licenses/by/4.0/
Metrics
How to Cite
