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Protective effects of Cinnamomum verum, Cinnamomum cassia and cinnamaldehyde against 6-OHDA-induced apoptosis in PC12 cells

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Abstract

Cinnamon (Cinnamomum verum and C. cassia) is a medicinal plant, widely-used as a culinary spice. It possesses various therapeutic effects and can slow down the progression of neurological disorders impressively. In this article, the effects of hydro-alcohol extract and essential oil of C. verum and C. cassia and its main bioactive component cinnamaldehyde, has been examined on 6-OHDA-exposed PC12 cells as an in vitro model of Parkinson's disease. The cytotoxicity and cell apoptosis has been induced by 6-OHDA in PC12 cells. The protective effect was determined by measuring cell viability, the amount of reactive oxygen species (ROS), and apoptosis. Cell viability and apoptosis were assessed using resazurin assay, flow cytometry of propidium iodide (PI) stained cells, and western blot analysis. 6-OHDA resulted in the death and apoptosis of cells while, pretreatment with the extract and essential oil of C. verum and C. cassia at 20 µg/ml and cinnamaldehyde at 5 and 10 µM for 24 h could significantly increase the viability (p < 0.001), and decrease ROS content (p < 0.05). Pretreatment with the extracts increased survivin and decreased cyt-c whereas, pretreatment with the essential oil decreased cyt-c, increased survivin, and reduced P-p44/42/p44/42 levels to a level near that of the related control. The extract and essential oil of C. verum and C. cassia can be effective against 6-OHDA cytotoxicity. It is suggested that, the synergistic effects of cinnamaldehyde and other components of extract and essential oil promote cinnamon’s medicinal properties.

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Abbreviations

PD:

Parkinson's disease

6-OHDA:

6-Hydroxydopamine

SN:

Substantia nigra

ROS:

Reactive oxygen species

DMSO:

Dimethyl sulfoxide

DCFH-DA:

2′,7′-dichlorofluorescin diacetate

PI:

Propidiumiodide

PBS:

Phosphate-buffer saline

BHT:

Butylated hydroxytoluene

SOD:

Superoxide dismutase

CAT:

Catalase

GOX:

Glucose oxidase

GSH:

Glutathione

ANOVA:

One-way analysis of variance

NO:

Nitric oxide

CC:

Cytotoxic concentration

H2O2 :

Hydrogen peroxide

TH:

Tyrosine hydroxylase

CA:

Cinnamic aldehyde

MPTP:

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

LC3:

Light chain 3

NaB:

Sodium benzoate

iNOS:

Inducible nitric oxide synthase

NF-κB:

Nuclear factor κB

PKA:

Protein kinase A

CREB:

Activation of cAMP response element binding

CNS:

Central nervous system

SOCS3:

Suppressor of cytokine signaling 3

IL:

Interleukin

TNF:

Tumor necrosis factor

CEppt:

Cinnamon extract precipitation

α-syn:

α-Synuclein

Cyt-c:

Cytochrome c

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Acknowledgements

This work was supported by Grant No. 951831 from Research Affairs of Mashhad University of Medical Sciences. The authors wish to thank Mr. Malaekeh for reading flow cytometry test samples.

Funding

This work has been supported by Grant No.951831 from the Research Affairs of Mashhad University of Medical Sciences, Mashhad, Iran.

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Authors and Affiliations

  1. Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Elham Ramazani & Zahra Tayarani-Najaran

  2. Department of Cell and Molecular Biology, Faculty of Science, Kosar University of Bojnord, Bojnord, Iran

    Elham Ramazani

  3. Department of Pharmacognosy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Mahdi YazdFazeli, Leila Mohtashami & Javad Asili

  4. Department of Traditional Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Seyed Ahmad Emami & Behjat Javadi

  5. Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, P.O. Box: 9188617871, Mashhad, Iran

    Zahra Tayarani-Najaran

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  1. Elham Ramazani
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Contributions

Elham Ramazani performed the experiments, computations, analyzed the data, and wrote the manuscript. Mahdi Yazd Fazeli performed the experiments and computations. Seyed Ahmad Emami, Behjat Javadi and Javad Asili conceived, designed, and supervised the project, wrote the manuscript and final approval of the manuscript. Leila Mohtashami performed the experiments and reviewed the manuscript. Zahra Tayarani-Najaran conceived, designed, and supervised the project, wrote the manuscript, provided financial support and final approval of the manuscript.

Corresponding author

Correspondence to Zahra Tayarani-Najaran.

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There is no conflict of interest in this study.

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This work is carried out on PC12 cells and there is no need for ethical clearance.

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Ramazani, E., YazdFazeli, M., Emami, S.A. et al. Protective effects of Cinnamomum verum, Cinnamomum cassia and cinnamaldehyde against 6-OHDA-induced apoptosis in PC12 cells. Mol Biol Rep 47, 2437–2445 (2020). https://doi.org/10.1007/s11033-020-05284-y

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