The effect of Nerolidol on the Superoxide Dismutase Enzyme Levels and mRNA Expression of CREB-1 Gene in Alzheimer's Model of Male Wistar Rats
Subject Areas : Journal of Animal BiologyPeyman Taheri 1 , Hajebrahimi Zahra 2 , Parichehreh Yaghmaei 3 , K. Parivar 4
1 - Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
2 - Aerospace Research Institute, Ministry of Science Research and Technology, Tehran, Iran
3 - Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
4 - Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
Keywords: Alzheimer's disease, Nerolidol, CREB-1 gene, Superoxide dismutase enzyme.,
Abstract :
Alzheimer's is the most important cause of neurological deterioration among elderly people, which is accompanied by the formation of amyloid plaques in the hippocampus region of the brain. One of the most important factors causing and progressing the disease is inflammation and oxidative stress. Nerolidol with antioxidant and anti-inflammatory properties is one of the secondary metabolites in some plants. CREB is one of the gene transcription factors that play a significant role in hippocampal neurons. The present study aimed to study the effect of nerolidol on the expression changes of the CREB-1 gene and superoxide dismutase enzyme in Alzheimer's model induced by beta-amyloid in male Wistar rats. The number of 48 male Wistar rats were divided into 8 groups including control, sham, Alzheimer's model, drug solvent, Alzheimer's with donepezil, Alzheimer's with nerolidol dose 50 and 100 mg/kg and protective group (treatment with nerolidol before induction of Alzheimer's). Biochemical analysis of the hippocampus, Real-Time PCR, and statistical analysis of data were performed using one-way analysis of variance and Tukey's test. Alzheimer's disease decreased CREB-1 gene expression and superoxide dismutase enzyme levels in the hippocampus. Donepezil and nerolidol, especially in the 100 dose and protective group, reduced Alzheimer's symptoms by increasing CREB-1 gene expression and superoxide dismutase enzyme levels. These findings indicate the antioxidant properties of nerolidol. Therefore, nerolidol may be effective in improving Alzheimer's disease and the damage caused by it, and it can probably be effective in preventing Alzheimer's in susceptible people with a family history of Alzheimer's.
1- Alberini C.M. 2009. Transcription factors in long‐term memory and synaptic plasticity. Physiological Reviews, 89:121–145.
2- Barnham K.J., Masters C.L., Bush A.I. 2004. Neurodegenerative diseases and oxidative stress. Nature Reviews Drug Discovery, 3:205-214.
3- Carvalho R.B.F. 2021. Technological development of an inclusion complex of nerolidol with cyclodextrin and evaluation of pharmacological properties. PhD. Post - Graduate Program in Biotechnology. Federal University of Piaui.
4- De Carvalho R.B.F., De Almeida A.A.C., Campelo N.B., Lellis D.R.O.D., Nunes L.C.C. 2018. Nerolidol and its pharmacological application in treating neurodegenerative diseases: A Review. Recent Patent on Biotechnology, 12(3):158-168.
5- Dinamarca M.C., Sagal J.P., Quintanilla R.A., Godoy J.A., Arrázola M.S., Inestrosa N.C. 2010. Amyloid-beta-Acetylcholinesterase complexes potentiate neurodegenerative changes induced by the Ab peptide. Implications for the pathogenesis of Alzheimer’s disease. Molecular neurodegeneration, 5)4):1-12.
6- Faux N.G., Rembach A., Wiley J., Ellis K.A., Ames D., Fowler C.J., Martins R.N., Pertile K.K., Rumble R.L., Trounson B., Masters C.L. 2014. An anemia of Alzheimer's disease. Molecular psychiatry, 19(11):1227-1240.
7- Francis P.T. 2005. The interplay of neurotransmitters in Alzheimer's disease. CNS Spectrums, 10:6-9.
8- Galasko D., Montine T.J. 2010. Biomarkers of oxidative damage and inflammation in Alzheimer’s disease. Biomarkers in Medicine, 4(1):27–36.
9- Gulisano W., Maugeri D., Baltrons M.A., Fà M., Amato A., Palmeri A., D'Adamio L., Grassi C., Devanand D.P., Honig L.S., Puzzo D., Arancio O. 2018. Role of Amyloid-β and Tau Proteins in Alzheimer's Disease: Confuting the Amyloid Cascade. Journal of Alzheimer’s Disease, 64(s1):S611-S631.
10- Iqubal A., Syed M.A., Najmi A.K., Azam F., Barreto G.E., Iqubal M.K., Ali J., Haque S.E. 2020. Nano-engineered nerolidol loaded lipid carrier delivery system attenuates cyclophosphamide neurotoxicity - Probable role of NLRP3 inflammasome and caspase-1. Experimental Neurology, 334:113464.
11- Kihara T., Shimohama S. 2004. Alzheimer's disease and acetylcholine receptors. Acta Neurobiologiae Experimentalis (Wars), 64(1):99-105.
12- Lapczynski A., Bhatia S.P., Letizia C.S., Api A.M. 2008. Fragrance material review on nerolidol (isomer unspecified). Food and Chemical Toxicology, 46(11): S247-S50.
13- Motaghinejad M., Mashayekh R., Motevalian M., Safari S. 2021. The possible role of CREB‐BDNF signaling pathway in neuroprotective effects of minocycline against alcohol induced neurodegeneration: Molecular and behavioral evidences. Fundamental & Clinical Pharmacology, 35(1):113–130.
14- Nogueira Neto J.D., Cardoso de Almeida A.A., Silva Oliveira J., Santos P.S., Pergentino de Sousa D., Mendes de Freitas R. 2013. Antioxidant effects of nerolidol in mice hippocampus after open field test. Neurochemical Research, 38:1861–1870.
15- Pepeu G., Giovannini M.G., Bracco L. 2013. Effect of cholinesterase inhibitors on attention. Chemico-Biological Interactions, 203:361–364.
16- Porsteinsson A., Grossberg G., Mintzer J., Olin J. 2008. Group MM-M-S. Memantine treatment in patients with mild to moderate Alzheimer's disease already receiving a cholinesterase inhibitor: a randomized, double-blind, placebocontrolled trial. Current Alzheimer Resarch, 5(1):83-89.
17- Pugazhenthi S., Wang M., Pham S., Sze C.I., Eckman C. B. 2011. Downregulation of CREB expression in alzheimer's brain and in Aβ‐treated rat hippocampal neurons. Molecular Neurodegeneration, 6(1):60-81.
18- Sberna G., Sáez-Valero J., Beyreuther K., Masters C.L., Small D.H. 1997. The amyloid beta-protein of Alzheimer's disease increases acetylcholinesterase expression by increasing intracellular calcium in embryonal carcinoma P19 cells. Journal of Neurochemistry, 69(3):1177-84.
19- Serrano-Pozo A., Frosch M.P., Masliah E., Hyman B.T. 2011. Neuropathological alterations in Alzheimer disease. Cold Spring Harbor Perspectives in Medicine, 1:a006189.
20- Silva M.P.N., Oliveira G.L.S., de Carvalho R.B.F., de Sousa D.P., Freitas R.M. , Pinto P.L.S., de Moraes J . 2014. Antischistosomal activity of the terpene nerolidol. Molecules, 19(3):3793-3803.
21- Taheri P., Yaghmaei P., Hajebrahimi Z., Parivar K. 2022. Neuroprotective effects of nerolidol against Alzheimer's disease in Wistar rats. Drug Development Research, 83(8):1858-1866.
22- Tamagno E., Guglielmotto M., Aragno M., Borghi R., Autelli R., Giliberto L., Muraca G., Danni O., Zhu X., Smith M.A., Perry G., Jo D.G., Mattson M.P., Tabaton M. 2008. Oxidative stress activates a positive feedback between the γ- and β-secretase cleavages of the β-amyloid precursor protein. Journal of Neurochemistry, 104(3): 683–695.
23- Wang H., Xu J., Lazarovici P., Quirion R., Zheng W. 2018. cAMP response element-binding protein (CREB): A possible signaling molecule link in the pathophysiology of Schizophrenia. Frontiers in Molecular Neuroscience, 11:255-276.
24- Yamada K., Nabeshima T. 2003. Brain-derived neurotrophic factor/TrkB signaling in memory processes. Journal of Pharmacological Sciences, 91(4):267–70.
25- Yang T., Zhang Y., Chen L., Thomas E.R., Yu W., Cheng B., Li X. 2023. The potential roles of ATF family in the treatment of Alzheimer's disease. Biomedicine and Pharmacotherapy, 161:114544.
