Cinnamaldehyde attenuates dopaminergic neuronal loss in substantia nigra and induces midbrain catalase activity in a mouse model of Parkinson’s disease

Document Type : Research Paper

Authors

1 Department of Anatomy, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran

2 Traditional Medicine Faculty, Iran University of Medical Sciences, Tehran, Iran

Abstract

Background and Objective: Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease that affects 3% of the population. PD involves a progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc) and subsequent loss of dopamine. Dopamine depletion leads to movement dysfunction and is accompanied with tremor, rigid muscles and impaired balance. Mechanisms of the pathogenesis of PD include oxidative stress and inflammation. Cinnamaldehyde acts as a powerful antioxidant and anti-inflammatory agent. This research is focused on the effects of cinnamaldehyde on neurons of SNc of mouse model of PD.
Materials and Methods: Adult male mice with an average weight of 25-35 g were divided into 4 groups of 5 each: group 1: control PBS, group2: MPTP, group 3: MPTP + cinnamaldehyde pretreatment (30 mg/kg), and group 4: MPTP + cinnamaldehyde treatment (30 mg/kg). Rotarod test was used to assess motor and balance of the mice. After behavioral studies, all the mice were anesthetized and perfused transcardially with 0.1 M PBS (pH=7.4) followed by 4% buffered paraformaldehyde fixative. The brains of the mice were removed and fixed in the paraformaldehyde and stained for TUNEL and IHC. Then the number of the apoptotic, TH+ and GFAP+ cells were counted. The level of MDA and catalase enzyme activity were also evaluated. Data was analyzed using SPSS software by one way of variance (ANOVA) and t-test.
Results: The results showed that groups 3 and 4 had significantly better locomotion than group 2 (p Conclusion: This study showed that cinnamaldehyde attenuates dopaminergic neuronal loss in substantia nigra and induces midbrain catalase activity in a mouse model of Parkinson’s disease.

Keywords


  1. Sveinbjornsdottir S. The clinical symptoms of Parkinson's disease. Journal of neuro chemistry.2016;139:318-324.
  2. Yacoubian TA,  Standaret DG.  Targets for  neuroprotection in  Parkinson’s disease. Biochemica et biophysica acta. 2009:1792(7): 676-687.
  3. Kalia, LV; Lang, AE. Parkinson's disease. Lancet. (2015); 386 (9996): 896–912.
  4. Munch G, Gerlach M, Sian J, Wong A, Riederer P. Advanced glycation end products in neurodegeneration: more than early markers of oxidative stress? Ann Neurol 1998;44:S85-8.
  5. Serra JA, Dominguez RO, de Lustig ES, Guareschi EM, Famulari AL, Bartolome EL,et al.Parkinson's disease is associated with oxidative stress: Comparison of peripheral antioxidant profiles in living Parkinson's Alzheimer's and vascular dementia patients. J Neurol Transm2001;108:1135-48.
  6. Yan MH,Wang X,Zhu X. Mitochondria defects and oxidative stress in Alzheimer disease and Parkinson disease. Free radical biology and medicine.2013: 62; 90-101.
  7. Mehraein F,  Sarbishegi M, Aslani, A. Evaluation of effect of oleuropein on skin wound healing in aged male Balb/c mice. Cell Journal. 2014: 16(1): 25-30.
  8. Babu P, Prabuseenivasan S, Ignacimuthu S. Cinnamaldehyde-A potential antidiabetic agent.Phytomedicine, 2007;14 : 15–22.
  9. Patra K, Bose S,Sarkar S, Rakshit J, Jana S, Mukherjee A, Roy A, Mandal DP, Bhattacharjee S. Amelioration cyclophosphamid induced myelosuppression and oxidative stress by cinnamic acid. Chemico biological interactions. 2012:195(3):231-239.
  10. Jana A, Modi KK, Roy A, Anderson JA, van Breemen RB, Pahan K (2013) Up-regulation of neurotrophic factors by cinnamon and its metabolite sodium benzoate: therapeutic implications for neurodegenerative disorders. J Neuroimmune Pharmacol 8:739–755.
  11. Azwanida NN. A review on the extraction methods use in medicinal plants, principle, strength and limitation. Med Aromat Plants. 2015;4(3);1-6.
  12. Luo Q, Peng G, Wang J, Wang Sh. The establishment of chronic Parkinson's disease in mouse model induced by MPTP. Journal of Chongqing medical university.2010(8):1149-1151.
  13. Ogura, T., et al., Impaired acquisition of skilled behavior in rotarod task by moderate depletion of striatal dopamine in a pre-symptomatic stage model of Parkinson's disease. Neurosci Res, 2005. 51(3): 299-308.
  14. Pyo JH, Jeong YK, Yeo S, Lee JH, Jeong MY, Kim SH, Choi YG, Lim S. Neuroprotective effect of trans-cinnamaldehyde on the 6-hydroxydopamine-induced dopaminergic injury. Biol Pharm Bull. 2013;36(12):1928-35.
  15. Chen YF, Wang YW, Huang WS, Lee MM, Wood WG, Leung YM, Tsai HY.  Trans- Cinnamaldehyde, An Essential Oil in Cinnamon Powder, Ameliorates Cerebral Ischemia- Induced Brain Injury via Inhibition of Neuroinflammation Through Attenuation of iNOS, COX-2 Expression and NFκ-B Signaling Pathway. Neuromolecular Med. 2016 Sep;18(3):322-33.
  16. Klein RL, Lewis MH, Muzyczka N, Meyer EM. Prevention of 6-hydroxydopamine-induced rotational behavior by BDNF somatic gene transfer. Brain Res.1999 Nov 20;847(2):314-20.
  17. Jana A, Modi KK, Roy A, Anderson JA, van Breemen RB, and Pahan K. Up- regulation of neurotrophic factors by cinnamon and its metabolite sodium benzoate: Therapeutic implications for neurodegenerative disorders. J Neuroimmune Pharmacol.
  18. Khasnavis S, Pahan K. Cinnamon treatment upregulates neuroprotective proteins Parkin and DJ-1 and protects dopaminergic neurons in a mouse model of Parkinson's disease. J Neuroimmune Pharmacol. 2014 Sep;9(4):569-81.
  19. Song F, Li H, Sun J, Wang S. Protective effects of cinnamic acid and cinnamic aldehyde  on isoproterenol-induced acute myocardial ischemia in rats. J Ethnopharmacol 2013; 150: 125-130.
  20.  Yuce A, Turk G, Ceribasi S, Sonmez M, Ciftci M, Guvence M. Effects of cinnamon (Cinnamomum zeylanicum) bark oil on testicular antioxidant values, apoptotic germ cell and sperm quality. Andrologica;2013:45(4):248-255.
  21. Pong K, Yangqi Y, Doctrow SR, Baudry M. Attenuation zinc induced intracellular dysfunction and neurotoxicity by a synthetic superoxidase / catalase mimic, in cultured cortical neurons. Brain Res.2002:950: 218-30.
  22. Panickar KS, Polansky MM, Graves DJ, Urban JF Jr, Anderson RA. A procyanidin type A trimer from cinnamon extract attenuates glial cell swelling and the reduction in glutamate uptake following ischemia-like injury in vitro.Neuroscience. 2012 Jan 27;202:87-98.
  23. Modi KK, Roy A, Brahmachari S, Rangasamy SB, Pahan K. Cinnamon and Its Metabolite Sodium Benzoate Attenuate the Activation of p21rac and Protect Memory and Learning in an Animal Model of Alzheimer’s Disease. PLoS One. 2015 Jun 23;10(6).
  24. Fu Y, Yang P, Zhao Y, Zhang L, Zhang ZH, Dong X, Wu Z, Xu Y, Chen Y. Trans-Cinnamaldehyde Inhibits Microglial Activation and Improves Neuronal Survival against Neuroinflammation in BV2 Microglial Cells with Lipopolysaccharide Stimulation. Evidence-Based Complementary and Alternative Medicine. 2017(19):1-12.
  25. Gowder S J. T, Halagowder D.Cinnamaldehyde induces behavioral and biochemical changes in the male albino wistar rat.Journal of Medical Sciences ; 2010: 3, (2): 101-109.
  26.  Snyder AM, Connor JR. Iron, the substantia nigra and related neurological disorders. Biochim Biophys Acta. 2009 Jul;1790(7):606-14.