The effects of aqueous cinnamon bark extract and cinnamaldehyde on neurons of substantia nigra and behavioral impairment in a mouse model of Parkinson’s disease

Document Type: Research Paper

Authors

1 Shahed Univ.

2 IUMS

Abstract

Background and Objective: Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons in substantia nigra. In recent years, there have been interests in the role of the free radical damage in PD. Cinnamon and its derivative, cinnamaldehyde acts as powerful antioxidant and anti-inflammatory agents. This research focused on the effects of cinnamon extract and cinnamaldehyde on neurons of SNc of a mouse model of Parkinson’s disease.
Materials and Methods: 45 adult male mice with an average weight of 25-35 g were divided into 9 groups of 5 each: group 1: control PBS, group 2: control serum, group 3: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), group 4: MPTP + low dose of cinnamon extract pretreatment (20 mg/kg), group 5: MPTP+ high dose of cinnamon extract pretreatment (40 mg/kg), group 6: MPTP + low dose of cinnamon extract treatment (20 mg/kg), group7: MPTP + high dose of cinnamon extract treatment (40 mg/kg), group 8: MPTP + cinnamaldehyde pretreatment (30 mg/kg), group 9: MPTP+ cinnamaldehyde treatment (30 mg/kg). Rotarod test was used to assess motor and balance of the mice. After behavioral studies, all mice were anesthetized and perfused transcardially with 0.1 M PBS (PH=7.4) followed by 4% buffered paraformaldehyde fixative. The brain of the mice were removed and fixed in the paraformaldehyde and stained for Nissl and the number of Nissl-stained neurons were counted. Data was analyzed using SPSS software by one way ANOVA.
Results: Aqueous cinnamon extract and cinnamaldehyde improved rotarod performance of MPTP-lesioned mice and prevented loss of Nissl-stained neurons of SNc of the midbrain.
Conclusion: These findings suggest that cinnamaldehye as a natural antioxidant may protect  neurons of SNc neurons against Parkinson’s disease.

Keywords



1. Yacoubian TA, Standaret DG. Targets for neuroprotection in Parkinson’s disease. Biochemica et Biophysica Acta 2009:1792(7):676-687.
2. Munch G, Gerlach M, Sian J, Wong A, Riederer P. Advanced glycation end products in neurodegeneration: more than early markers of oxidative stress? Annals of Neurology 1998;44:S85-8.
3. 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. Journal of Neural Transmission 2001;108:1135-48.
4. Yan MH,Wang X,Zhu X. Mitochondria defectsand oxidative stress in Alzheimer disease and Parkinson disease. Free Radical Biology and Medicine 2013: 62; 90-101.
5. 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.
6. Ravindran P BK. Shylaja M,ed Cinnamon and Cassia: The genus Cinnamomum. Danvers, Ma: CRC;2005.
7. Patra K, Bose S, Sarkar S, Rakshit J, Jana S, Mukherjee A, et al. Amelioration of cyclophosphamide induced myelosuppression and oxidative stress by cinnamic acid. Chemico-biological Interactions 2012:195(3):231-239.
8. LI Y-q, Kong D-x, Wa H. Analysis and evaluation of essential oil components of cinnamon barks using GC-MS and FTIR spectroscopy. Industrial Crops and Products 2013:41;269-278.
9. Chauhan V, Chauhan A. Oxidative stress in Alzheimer’s disease. Pathophysiology 2006;13(3):195-208.
10. Jana A, Modi KK, Roy A, Anderson JA, van Breemen RB, Pahan K. Up-regulation of neurotrophic factors by cinnamon and its metabolite sodium benzoate: therapeutic implications for neurodegenerative disorders. The Journal of Neuroimmune Pharmacology 2013; 8:739-755.
11. Azwanida NN. A review on the extraction methods use in medicinal plants, principle, strength and limitation. Medicinal and Aromatic Plants 2015;4(3);1-6.
12. Ogura T, Ogata M, Akita H, Jitsuki S, Akiba L, Noda K, 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. Neuroscience Research 2005; 51(3): 299-308.
13. Pyo JH, Jeong YK, Yeo S, Lee JH, Jeong MY, Kim SH, et al. Neuroprotective effect of trans-cinnamaldehyde on the 6-hydroxydopamine-induced dopaminergic injury. Biological and Pharmaceutical Bulletin 2013;36(12):1928-35.
14. Chen YF, Wang YW, Huang WS, Lee MM, Wood WG, Leung YM, et al. 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 Medicine 2016;18(3):322-33.
15. Klein RL, Lewis MH, Muzyczka N, Meyer EM. Prevention of 6-hydroxydopamine-induced rotational behavior by BDNF somatic gene transfer. Brain Research 1999; 847(2):314-20.
16. 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. Journal of Neuroimmune Pharmacology 2013;8(3):739-55.
17. 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. Journal of Neuroimmune Pharmacology 2014;9(4):569-81.
18. Davies KJ, Shringarpure R. Preferential degradation of oxidized proteins by the 20S proteasome may be inhibited in aging and in inflammatory neuromuscular diseases. Neurology 2006;66:S93-6.
19. Gowder SJT, Halagowder D. Cinnamaldehyde induces behavioral and biochemical changes in the male albino Wistar rat. Journal of Medical Sciences 2010;3:101-109.
20. Ghosh A, Roy A, Liu X, Kordower JH, Mufson EJ, Hartley DM, et al. Selective inhibition of NF-κB activation prevents dopaminergic neuronal loss in a mouse model of Parkinson's disease. Proceedings of the National Academy of Sciences of the United States of America 2007:104:18754-18759.
21. Brahmachari S, Jana A, Pahan K. Sodium benzoate, a metabolite of cinnamon and a food additive, reduces microglial and astroglial inflammatory responses. Journal of Immunology 2009; 183: 5917-5927.