Anatomy and Cell Biology

Korean Association of Anatomists (대한해부학회)
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Honey and levodopa comparably preserved substantia nigra pars compacta neurons through the modulation of nuclear factor erythroid 2-related factor 2 signaling pathway in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease model

  • Fatimo Ajoke Sulaimon (Department of Anatomy, Faculty of Basic Medical Sciences, College of Health Sciences, University of Ilorin) ;
  • Ruqayyah Yetunde Ibiyeye (Department of Anatomy, Faculty of Basic Medical Sciences, College of Health Sciences, Kwara State University) ;
  • Aminu Imam (Department of Anatomy, Faculty of Basic Medical Sciences, College of Health Sciences, University of Ilorin) ;
  • Aboyeji Lukuman Oyewole (Department of Physiology, Faculty of Basic Medical Sciences, College of Health Sciences, University of Ilorin) ;
  • Abubakar Lekan Imam (Department of Anatomy, Faculty of Basic Medical Sciences, College of Health Sciences, University of Ilorin) ;
  • Monsur Shehu (Department of Anatomy, Faculty of Basic Medical Sciences, College of Health Sciences, University of Ilorin) ;
  • Sikiru Abayomi Biliaminu (Department of Chemical Pathology, Faculty of Basic Clinical Sciences, College of Health Sciences, University of Ilorin) ;
  • Risikat Eniola Kadir (Department of Anatomy, Faculty of Basic Medical Sciences, College of Health Sciences, University of Ilorin) ;
  • Gabriel Olaiya Omotoso (Department of Anatomy, Faculty of Basic Medical Sciences, College of Health Sciences, University of Ilorin) ;
  • Moyosore Salihu Ajao (Department of Anatomy, Faculty of Basic Medical Sciences, College of Health Sciences, University of Ilorin)
  • Received : 2024.02.05
  • Accepted : 2024.05.09
  • Published : 2024.09.30
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Abstract

Parkinson's disease (PD) affects about 8.5 million individuals worldwide. Oxidative and inflammatory cascades are implicated in the neurological sequels, that are mostly unresolved in PD treatments. However, proper nutrition offers one of the most effective and least costly ways to decrease the burden of many diseases and their associated risk factors. Moreover, prevention may be the best response to the progressive nature of PD, thus, the therapeutic novelty of honey and levodopa may be prospective. This study aimed to investigate the neuroprotective role of honey and levodopa against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced oxidative stress. Fifty-four adult male Swiss mice were divided into control and PD model groups of 27 mice. Each third of the control mice either received phosphate buffered saline, honey, or levodopa for 21 days. However, each third of the PD models was either pretreated with honey and levodopa or not pretreated. Behavioral studies and euthanasia were conducted 2 and 8 days after MPTP administration respectively. The result showed that there were significantly (P<0.05) higher motor activities in the PD models pretreated with the honey as well as levodopa. furthermore, the pretreatments protected the midbrain against the chromatolysis and astrogliosis induced by MPTP. The expression of antioxidant markers (glutathione [GSH] and nuclear factor erythroid 2-related factor 2 [Nrf2]) was also significantly upregulated in the pretreated PD models. It is thus concluded that honey and levodopa comparably protected the substantia nigra pars compacta neurons against oxidative stress by modulating the Nrf2 signaling molecule thereby increasing GSH level to prevent MPTP-induced oxidative stress.

Keywords

Acknowledgement

We hereby acknowledge the Dr. Ijomone, O.M of Neurostein Lab, Ondo, Adeyemo E.A, Emaye M.A and Yussuf R.A. Olaoye J, Jimoh H.B, and Ashir F, for their technical support. The technical team of the central research laboratory, Tanke is also well-appreciated.

References

  1. World Health Organization (WHO). Ageing and health [Internet]. WHO; 2022 Oct 1 [cited 2023 Dec 29]. Available from: https://www.who.int/news-room/fact-sheets/detail/ageing-andhealth
  2. Yang W, Hamilton JL, Kopil C, Beck JC, Tanner CM, Albin RL, Ray Dorsey E, Dahodwala N, Cintina I, Hogan P, Thompson T. Current and projected future economic burden of Parkinson's disease in the U.S. NPJ Parkinsons Dis 2020;6:15.
  3. Tysnes OB, Storstein A. Epidemiology of Parkinson's disease. J Neural Transm (Vienna) 2017;124:901-5. https://doi.org/10.1007/s00702-017-1686-y
  4. Simon DK, Tanner CM, Brundin P. Parkinson disease epidemiology, pathology, genetics, and pathophysiology. Clin Geriatr Med 2020;36:1-12. https://doi.org/10.1016/j.cger.2019.08.002
  5. Bove C, Travagli RA. Neurophysiology of the brain stem in Parkinson's disease. J Neurophysiol 2019;121:1856-64. https://doi.org/10.1152/jn.00056.2019
  6. Kouli A, Torsney KM, Kuan WL. Parkinson's disease: etiology, neuropathology, and pathogenesis. In: Stoker TB, Greenland JC, editors. Parkinson's disease: pathogenesis and clinical aspects. Codon Publications; 2018.
  7. Jenner P, Olanow CW. Oxidative stress and the pathogenesis of Parkinson's disease. Neurology 1996;47(6 Suppl 3):S161-70.
  8. Magrinelli F, Picelli A, Tocco P, Federico A, Roncari L, Smania N, Zanette G, Tamburin S. Pathophysiology of motor dysfunction in Parkinson's disease as the rationale for drug treatment and rehabilitation. Parkinsons Dis 2016;2016:9832839.
  9. Ball N, Teo WP, Chandra S, Chapman J. Parkinson's disease and the environment. Front Neurol 2019;10:218.
  10. Nag N, Jelinek GA. A narrative review of lifestyle factors associated with Parkinson's disease risk and progression. Neurodegener Dis 2019;19:51-9. https://doi.org/10.1159/000502292
  11. Teodoro AJ. Bioactive compounds of food: their role in the prevention and treatment of diseases. Oxid Med Cell Longev 2019; 2019:3765986.
  12. ParkinsonsDisease.net. Dietary supplements for Parkinson's disease [Internet]. ParkinsonsDisease.net.; 2017 Mar 17 [cited 2023 Dec 29]. Available from: https://parkinsonsdisease.net/treatment/complementary-alternative-supplements
  13. Iranshahy M, Javadi B, Sahebkar A. Protective effects of functional foods against Parkinson's disease: a narrative review on pharmacology, phytochemistry, and molecular mechanisms. Phytother Res 2022;36:1952-89. https://doi.org/10.1002/ptr.7425
  14. Ali AM, Kunugi H. Bee honey protects astrocytes against oxidative stress: a preliminary in vitro investigation. Neuropsychopharmacol Rep 2019;39:312-4. https://doi.org/10.1002/npr2.12079
  15. Kesavan P, Banerjee A, Banerjee A, Murugesan R, Marotta F, Pathak S. An overview of dietary polyphenols and their therapeutic effects. In: Watson RR, Preedy VR, Zibadi S, editors. Polyphenols: mechanisms of action in human health and disease. Elsevier; 2018. p.221-35.
  16. Glick D. Methods of biochemical analysis. Wiley; 1954.
  17. Percario S, da Silva Barbosa A, Varela ELP, Gomes ARQ, Ferreira MES, de Nazare Araujo Moreira T, Dolabela MF. Oxidative stress in Parkinson's disease: potential benefits of antioxidant supplementation. Oxid Med Cell Longev 2020;2020:2360872.
  18. Aznavour N, Cendres-Bozzi C, Lemoine L, Buda C, Sastre JP, Mincheva Z, Zimmer L, Lin JS. MPTP animal model of Parkinsonism: dopamine cell death or only tyrosine hydroxylase impairment? A study using PET imaging, autoradiography, and immunohistochemistry in the cat. CNS Neurosci Ther 2012;18:934-41. https://doi.org/10.1111/cns.12009
  19. Zhou JS, Zhu Z, Wu F, Zhou Y, Sheng R, Wu JC, Qin ZH. NADPH ameliorates MPTP-induced dopaminergic neurodegeneration through inhibiting p38MAPK activation. Acta Pharmacol Sin 2019;40:180-91.
  20. Abdulmajeed WI, Sulieman HB, Zubayr MO, Imam A, Amin A, Biliaminu SA, Oyewole LA, Owoyele BV. Honey prevents neurobehavioural deficit and oxidative stress induced by lead acetate exposure in male Wistar rats- a preliminary study. Metab Brain Dis 2016;31:37-44.
  21. Angelopoulou E, Pyrgelis ES, Piperi C. Neuroprotective potential of chrysin in Parkinson's disease: molecular mechanisms and clinical implications. Neurochem Int 2020;132:104612.
  22. Lin MW, Lin CC, Chen YH, Yang HB, Hung SY. Celastrol inhibits dopaminergic neuronal death of Parkinson's disease through activating mitophagy. Antioxidants (Basel) 2019;9:37.
  23. Adeniyi IA, Babalola KT, Adekoya VA, Oyebanjo O, Ajayi AM, Onasanwo SA. Neuropharmacological effects of honey in lipopolysaccharide-induced neuroinflammation, cognitive impairment, anxiety and motor impairment. Nutr Neurosci 2023;26:511-24. https://doi.org/10.1080/1028415X.2022.2063578
  24. Zhang ZN, Hui Z, Chen C, Liang Y, Tang LL, Wang SL, Xu CC, Yang H, Zhang JS, Zhao Y. Neuroprotective effects and related mechanisms of echinacoside in MPTP-induced PD mice. Neuropsychiatr Dis Treat 2021;17:1779-92. https://doi.org/10.2147/NDT.S299685
  25. Zhao Q, Cai D, Bai Y. Selegiline rescues gait deficits and the loss of dopaminergic neurons in a subacute MPTP mouse model of Parkinson's disease. Int J Mol Med 2013;32:883-91. https://doi.org/10.3892/ijmm.2013.1450
  26. Geldenhuys WJ, Guseman TL, Pienaar IS, Dluzen DE, Young JW. A novel biomechanical analysis of gait changes in the MPTP mouse model of Parkinson's disease. PeerJ 2015;3:e1175.
  27. Li S, Pu XP. Neuroprotective effect of kaempferol against a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease. Biol Pharm Bull 2011;34:1291-6. https://doi.org/10.1248/bpb.34.1291
  28. Mijanur Rahman M, Gan SH, Khalil MI. Neurological effects of honey: current and future prospects. Evid Based Complement Alternat Med 2014;2014:958721.
  29. Kotian SR, Bhat KMR, Padma D, Pai KSR. Influence of traditional medicines on the activity of keratinocytes in wound healing: an in-vitro study. Anat Cell Biol 2019;52:324-32. https://doi.org/10.5115/acb.19.009
  30. Hornykiewicz O. The discovery of dopamine deficiency in the parkinsonian brain. In: Riederer P, Reichmann H, Youdim MBH, Gerlach M, editors. Parkinson's disease and related disorders. Springer Vienna; 2006. p.9-15.
  31. Gao JX, Li Y, Wang SN, Chen XC, Lin LL, Zhang H. Overexpression of microRNA-183 promotes apoptosis of substantia nigra neurons via the inhibition of OSMR in a mouse model of Parkinson's disease. Int J Mol Med 2019;43:209-20.
  32. Castelli V, Grassi D, Bocale R, d'Angelo M, Antonosante A, Cimini A, Ferri C, Desideri G. Diet and brain health: which role for polyphenols? Curr Pharm Des 2018;24:227-38. https://doi.org/10.2174/1381612824666171213100449
  33. Yasuda Y, Shimoda T, Uno K, Tateishi N, Furuya S, Yagi K, Suzuki K, Fujita S. The effects of MPTP on the activation of microglia/astrocytes and cytokine/chemokine levels in different mice strains. J Neuroimmunol 2008;204:43-51. https://doi.org/10.1016/j.jneuroim.2008.08.003
  34. O'Callaghan JP, Seidler FJ. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced astrogliosis does not require activation of ornithine decarboxylase. Neurosci Lett 1992;148:105-8. https://doi.org/10.1016/0304-3940(92)90815-O
  35. Serra PA, Sciola L, Delogu MR, Spano A, Monaco G, Miele E, Rocchitta G, Miele M, Migheli R, Desole MS. The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induces apoptosis in mouse nigrostriatal glia. Relevance to nigral neuronal death and striatal neurochemical changes. J Biol Chem 2002;277:34451-61. https://doi.org/10.1074/jbc.M202099200
  36. MacMahon Copas AN, McComish SF, Fletcher JM, Caldwell MA. The pathogenesis of Parkinson's disease: a complex interplay between astrocytes, microglia, and T lymphocytes? Front Neurol 2021;12:666737.
  37. Minden-Birkenmaier BA, Cherukuri K, Smith RA, Radic MZ, Bowlin GL. Manuka honey modulates the inflammatory behavior of a dHL-60 neutrophil model under the cytotoxic limit. Int J Biomater 2019;2019:6132581.
  38. Middeldorp J, Hol EM. GFAP in health and disease. Prog Neurobiol 2011;93:421-43. https://doi.org/10.1016/j.pneurobio.2011.01.005
  39. Manoharan S, Guillemin GJ, Abiramasundari RS, Essa MM, Akbar M, Akbar MD. The role of reactive oxygen species in the pathogenesis of Alzheimer's disease, Parkinson's disease, and Huntington's disease: a mini review. Oxid Med Cell Longev 2016;2016:8590578.
  40. Gluck MR, Krueger MJ, Ramsay RR, Sablin SO, Singer TP, Nicklas WJ. Characterization of the inhibitory mechanism of 1-methyl-4-phenylpyridinium and 4-phenylpyridine analogs in inner membrane preparations. J Biol Chem 1994;269:3167-74. https://doi.org/10.1016/S0021-9258(17)41844-8
  41. Ahmad A, Khan RA, Mesaik MA. Anti inflammatory effect of natural honey on bovine thrombin-induced oxidative burst in phagocytes. Phytother Res 2009;23:801-8. https://doi.org/10.1002/ptr.2648
  42. Hunter M, Kellett J, D'Cunha NM, Toohey K, McKune A, Naumovski N. The effect of honey as a treatment for oral ulcerative lesions: a systematic review. Explor Res Hypothesis Med 2020;5:27-37.
  43. Ayala A, Munoz MF, Arguelles S. Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid Med Cell Longev 2014;2014:360438.
  44. Liu C, Kershberg L, Wang J, Schneeberger S, Kaeser PS. Dopamine secretion is mediated by sparse active zone-like release sites. Cell 2018;172:706-18.e15. https://doi.org/10.1016/j.cell.2018.01.008
  45. Agil A, Duran R, Barrero F, Morales B, Arauzo M, Alba F, Miranda MT, Prieto I, Ramirez M, Vives F. Plasma lipid peroxidation in sporadic Parkinson's disease. Role of the L-dopa. J Neurol Sci 2006;240:31-6. https://doi.org/10.1016/j.jns.2005.08.016
  46. Adekeye AO, Irawo GJ, Fafure AA. Ficus exasperata Vahl leaves extract attenuates motor deficit in vanadium-induced parkinsonism mice. Anat Cell Biol 2020;53:183-93. https://doi.org/10.5115/acb.19.205
  47. Erejuwa OO, Sulaiman SA, Ab Wahab MS, Sirajudeen KN, Salleh S, Gurtu S. Honey supplementation in spontaneously hypertensive rats elicits antihypertensive effect via amelioration of renal oxidative stress. Oxid Med Cell Longev 2012;2012:374037.
  48. Awasthi YC, Chaudhary P, Vatsyayan R, Sharma A, Awasthi S, Sharma R. Physiological and pharmacological significance of glutathione-conjugate transport. J Toxicol Environ Health B Crit Rev 2009;12:540-51. https://doi.org/10.1080/10937400903358975
  49. Aoyama K, Matsumura N, Watabe M, Nakaki T. Oxidative stress on EAAC1 is involved in MPTP-induced glutathione depletion and motor dysfunction. Eur J Neurosci 2008;27:20-30. https://doi.org/10.1111/j.1460-9568.2007.05979.x
  50. Wang Y, Li D, Cheng N, Gao H, Xue X, Cao W, Sun L. Antioxidant and hepatoprotective activity of vitex honey against paracetamol induced liver damage in mice. Food Funct 2015;6:2339-49. https://doi.org/10.1039/C5FO00345H
  51. Younes-Mhenni S, Frih-Ayed M, Kerkeni A, Bost M, Chazot G. Peripheral blood markers of oxidative stress in Parkinson's disease. Eur Neurol 2007;58:78-83. https://doi.org/10.1159/000103641
  52. Brandes MS, Zweig JA, Tang A, Gray NE. NRF2 activation ameliorates oxidative stress and improves mitochondrial function and synaptic plasticity, and in A53T α-synuclein hippocampal neurons. Antioxidants (Basel) 2021;11:26.
  53. Almasaudi SB, Abbas AT, Al-Hindi RR, El-Shitany NA, Abdel-Dayem UA, Ali SS, Saleh RM, Al Jaouni SK, Kamal MA, Harakeh SM. Manuka honey exerts antioxidant and anti-inflammatory activities that promote healing of acetic acidinduced gastric ulcer in rats. Evid Based Complement Alternat Med 2017;2017:5413917.
  54. Esteras N, Dinkova-Kostova AT, Abramov AY. Nrf2 activation in the treatment of neurodegenerative diseases: a focus on its role in mitochondrial bioenergetics and function. Biol Chem 2016;397:383-400.
  55. von Otter M, Landgren S, Nilsson S, Celojevic D, Bergstrom P, Hakansson A, Nissbrandt H, Drozdzik M, Bialecka M, Kurzawski M, Blennow K, Nilsson M, Hammarsten O, Zetterberg H. Association of Nrf2-encoding NFE2L2 haplotypes with Parkinson's disease. BMC Med Genet 2010;11:36.
  56. Anandhan A, Nguyen N, Syal A, Dreher LA, Dodson M, Zhang DD, Madhavan L. NRF2 loss accentuates Parkinsonian pathology and behavioral dysfunction in human α-synuclein overexpressing mice. Aging Dis 2021;12:964-82. https://doi.org/10.14336/AD.2021.0511
  57. Chen PC, Vargas MR, Pani AK, Smeyne RJ, Johnson DA, Kan YW, Johnson JA. Nrf2-mediated neuroprotection in the MPTP mouse model of Parkinson's disease: critical role for the astrocyte. Proc Natl Acad Sci U S A 2009;106:2933-8. https://doi.org/10.1073/pnas.0813361106
  58. Alvarez-Suarez JM, Giampieri F, Cordero M, Gasparrini M, Forbes-Hernandez TY, Mazzoni L, Afrin S, Beltran-Ayala P, Gonzalez-Paramas AM, Santos-Buelga C, Varela-Lopez A, Quiles JL, Battino M. Activation of AMPK/Nrf2 signalling by Manuka honey protects human dermal fibroblasts against oxidative damage by improving antioxidant response and mitochondrial function promoting wound healing. J Funct Foods 2016;25:38-49. https://doi.org/10.1016/j.jff.2016.05.008
  59. Ranneh Y, Akim AM, Hamid HA, Khazaai H, Fadel A, Mahmoud AM. Stingless bee honey protects against lipopolysaccharide induced-chronic subclinical systemic inflammation and oxidative stress by modulating Nrf2, NF-κB and p38 MAPK. Nutr Metab (Lond) 2019;16:15.