Volume 28, Issue 126 (January & February 2020)                   J Adv Med Biomed Res 2020, 28(126): 23-32 | Back to browse issues page


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Ataei N, Soodi M, Hajimehdipoor H, Akbari S, Alimohammadi M. Cerasus microcarpa and Amygdalus scoparia Methanolic Extract Protect Cultured Cerebellar Granule Neurons Against β-amyloid-induced Toxicity and Oxidative Stress. J Adv Med Biomed Res 2020; 28 (126) :23-32
URL: http://journal.zums.ac.ir/article-1-5807-en.html
1- Dept. of Toxicology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
2- Dept. of Toxicology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran , soodi@modares.ac.ir
3- Traditional Medicine and Materia Medica Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Abstract:   (146284 Views)
 Background & Objective:  Beta-amyloid peptide (Aβ) causes neural cell death and has a pivotal role in the progression of Alzheimer’s disease (AD). The prevention of Aβ-induced toxicity is a target for agents intend to treat Alzheimer’s disease. Our previous in vitro study indicated anti-cholinesterase and anti-oxidant activity of Amygdalus scoparia and Cerasus microcarpa methanolic extracts. In the present study, their neuroprotective effects against Aβ-induced toxicity are investigated.
 Materials & Methods:  The methanolic extracts of the aerial parts of A. scoparia and C. microcarpa were prepared by the maceration method. In the culture, mature cerebellar granule neurons (CGNs) were exposed to Aβ alone or in combination with different concentrations of extracts and incubated for 24 hours, and cell viability was measured by the MTT assay. Oxidative stress markers and AChE activity were also measured. Then, the AChE activity of cultured neurons was measured after incubation with different concentrations of extracts. The LD50 values of extracts were estimated using the limit test.
Results:  The co-incubation of C. microcarpa and A. scoparia extracts with Aβ protected CGNs against Aβ-induced cell death and ameliorated Aβ-induced oxidative stress. The AChE activity of cultured neurons was inhibited by both extracts in a dose-dependent manner. LD50 was estimated as being above 2000 mg/kg for both extracts.
Conclusion:  Both extracts attenuated Aβ-induced cell death by ameliorating oxidative stress. Also, the inhibitory effect of extracts on AChE activity might have been involved. Based on these results, these extracts may have therapeutic effects on Alzheimer’s disease.  However, further investigations are recommended.
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✅ Both extracts attenuated Aβ-induced cell death by ameliorating oxidative stress. Also, the inhibitory effect of extracts on AChE activity might have been involved. Based on these results, these extracts may have therapeutic effects on Alzheimer’s disease.  However, further investigations are recommended.

Type of Study: Original Article | Subject: Pharmacology
Received: 2019/10/16 | Accepted: 2019/11/15 | Published: 2020/01/5

References
1. Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer's disease at 25 years. EMBO Mol Med. 2016;8(6):595-608. [DOI:10.15252/emmm.201606210]
2. De Strooper B, Karran E. The cellular phase of Alzheimer's disease. Cell. 2016;164(4):603-15. [DOI:10.1016/j.cell.2015.12.056]
3. Irvine GB, El-Agnaf OM, Shankar GM, Walsh DM. Protein aggregation in the brain: The molecular basis for Alzheimer's and Parkinson's diseases. Molec Med. 2008;14(7):451-64. [DOI:10.2119/2007-00100.Irvine]
4. Sun X, Chen WD, Wang YD. Beta-Amyloid: the key peptide in the pathogenesis of Alzheimer's disease. Front Pharmacol. 2015;6:221. [DOI:10.3389/fphar.2015.00221]
5. Huang X, Atwood CS, Hartshorn MA, et al. The A beta peptide of Alzheimer's disease directly produces hydrogen peroxide through metal ion reduction. Biochem. 1999;38(24):7609-16. [DOI:10.1021/bi990438f]
6. Zhu X, Su B, Wang X, Smith MA, Perry G. Causes of oxidative stress in Alzheimer disease. Cell and Molec Life Sci. 2007;64(17):2202-10. [DOI:10.1007/s00018-007-7218-4]
7. Cheignon C, Tomas M, Bonnefont-Rousselot D, Faller P, Hureau C, Collin F. Oxidative stress and the amyloid beta peptide in Alzheimer's disease. Redox Biol. 2018;14:450-64. [DOI:10.1016/j.redox.2017.10.014]
8. Ferreira ME, de Vasconcelos AS, da Costa Vilhena T, et al. Oxidative stress in Alzheimer's disease: Should we keep trying antioxidant therapies? Cell Molec Neurobiol. 2015;35(5):595-614. [DOI:10.1007/s10571-015-0157-y]
9. Li FJ, Shen L, Ji HF. Dietary intakes of vitamin E, vitamin C, and beta-carotene and risk of Alzheimer's disease: a meta-analysis. J Alzheimer's Dis. 2012;31(2):253-8. [DOI:10.3233/JAD-2012-120349]
10. Gustafson DR, Clare Morris M, Scarmeas N, et al. New perspectives on Alzheimer's disease and nutrition. J Alzheimer's Dis. 2015;46(4):1111-27. [DOI:10.3233/JAD-150084]
11. Amato A, Terzo S, Mule F. Natural compounds as beneficial antioxidant agents in neurodegenerative disorders: A focus on Alzheimer's disease. Antioxidants. 2019;8(12). [DOI:10.3390/antiox8120608]
12. Deardorff WJ, Feen E, Grossberg GT. The use of cholinesterase inhibitors across all stages of Alzheimer's disease. Drugs & Aging. 2015;32(7):537-47. [DOI:10.1007/s40266-015-0273-x]
13. Batool A, Kamal MA, Rizvi SMD, Rashid S. Topical discoveries on multi-target approach to manage Alzheimer's disease. Curr Drug Metab. 2018;19(8):704-13. [DOI:10.2174/1389200219666180305152553]
14. Ambure P, Bhat J, Puzyn T, Roy K. Identifying natural compounds as multi-target-directed ligands against Alzheimer's disease: an in silico approach. J Biomolec Struct & Dynamics. 2019;37(5):1282-306. [DOI:10.1080/07391102.2018.1456975]
15. Schulz V, Hänsel R, Blumenthal M, Tyler VE. Rational phytotherapy: A reference guide for physicians and pharmacists: Springer Science & Business Media; 2004. [DOI:10.1007/978-3-662-09666-6]
16. Hamaguchi T, Ono K, Murase A, Yamada M. Phenolic compounds prevent Alzheimer's pathology through different effects on the amyloid-β aggregation pathway. Am J Pathol. 2009;175(6):2557-65. [DOI:10.2353/ajpath.2009.090417]
17. Golkar A, Nasirpour A, Keramat J. β-lactoglobulin-Angum gum (Amygdalus Scoparia Spach) complexes: Preparation and emulsion stabilization. J Disper Sci Technol. 2015;36(5):685-94. [DOI:10.1080/01932691.2014.919587]
18. Hashemnia M, Nikousefat Z, Yazdani-Rostam M. Antidiabetic effect of Pistacia atlantica and Amygdalus scoparia in streptozotocin-induced diabetic mice. Compar Clin Pathol. 2015;24(6):1301-6. [DOI:10.1007/s00580-015-2068-1]
19. Mosaddegh M, Naghibi F, Moazzeni H, Pirani A, Esmaeili S. Ethnobotanical survey of herbal remedies traditionally used in Kohghiluyeh va Boyer Ahmad province of Iran. J Ethnopharmacol. 2012;141(1):80-95. [DOI:10.1016/j.jep.2012.02.004]
20. Hajimehdipoor H, Ara L, Moazzeni H, Esmaeili S. Evaluating the antioxidant and acetylcholinesterase inhibitory activities of some plants from Kohgiluyeh va Boyerahmad province, Iran. Res J Pharmacog. 2016;3(4):1-7.
21. Soodi M, Hajimehdipoor H, Ataei N, Akbari S. Study of theprotective effects of seven Iranian medicinal plant extracts against Beta-Amyloid induced cytotoxicity in PC12 Cells. Pathobiol Res. 2016;19(3):45-58.
22. Contestabile A. Cerebellar granule cells as a model to study mechanisms of neuronal apoptosis or survival in vivo and in vitro. Cerebellum. 2002;1(1):41-55. [DOI:10.1080/147342202753203087]
23. Wei H, Leeds PR, Qian Y, Wei W, Chen R-w, Chuang D-M. β-Amyloid peptide-induced death of PC 12 cells and cerebellar granule cell neurons is inhibited by long-term lithium treatment. Europ J Pharmacol. 2000;392(3):117-23. [DOI:10.1016/S0014-2999(00)00127-8]
24. Soodi M, Dashti A, Hajimehdipoor H, Akbari S, Ataei N. Melissa officinalis acidic fraction protects cultured cerebellar granule neurons against beta amyloid-induced apoptosis and oxidative stress. Cell J. 2017;18(4):556.
25. Sylvester PW. Optimization of the tetrazolium dye (MTT) colorimetric assay for cellular growth and viability. Drug design and discovery: Springer; 2011. p. 157-68. [DOI:10.1007/978-1-61779-012-6_9]
26. Wang H, Joseph JA. Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader. Free Radical Biol Med. 1999;27(5-6):612-6. [DOI:10.1016/S0891-5849(99)00107-0]
27. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytic Biochem. 1976;72(1-2):248-54. [DOI:10.1016/0003-2697(76)90527-3]
28. Ellman GL, Courtney KD, Andres V, Feather-Stone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol. 1961;7:88-95. [DOI:10.1016/0006-2952(61)90145-9]
29. Naoi M, Shamoto-Nagai M, Maruyama W. Neuroprotection of multifunctional phytochemicals as novel therapeutic strategy for neurodegenerative disorders: Antiapoptotic and antiamyloidogenic activities by modulation of cellular signal pathways. Future Neurol. 2019;14(1):FNL9. [DOI:10.2217/fnl-2018-0028]
30. Camilleri A, Zarb C, Caruana M, et al. Mitochondrial membrane permeabilisation by amyloid aggregates and protection by polyphenols. Biochimica et biophysica acta. 2013;1828(11):2532-43. [DOI:10.1016/j.bbamem.2013.06.026]
31. Naoi M, Wu Y, Shamoto-Nagai M, Maruyama W. Mitochondria in neuroprotection by phytochemicals: Bioactive polyphenols modulate mitochondrial apoptosis system, function and structure. Int J Molec Sci. 2019;20(10):2451. [DOI:10.3390/ijms20102451]
32. Arancibia S, Silhol M, Moulière F, et al. Protective effect of BDNF against beta-amyloid induced neurotoxicity in vitro and in vivo in rats. Neurobiol Dis. 2008;31(3):316-26. [DOI:10.1016/j.nbd.2008.05.012]
33. Mansuri ML, Parihar P, Solanki I, Parihar MS. Flavonoids in modulation of cell survival signalling pathways. Genes Nutr. 2014;9(3):400. [DOI:10.1007/s12263-014-0400-z]
34. Murray AP, Faraoni MB, Castro MJ, Alza NP, Cavallaro V. Natural AChE inhibitors from plants and their contribution to Alzheimer's disease therapy. Current Neuropharmacol. 2013;11(4):388-413. [DOI:10.2174/1570159X11311040004]
35. Roseiro LB, Rauter AP, Serralheiro MLM. Polyphenols as acetylcholinesterase inhibitors: structural specificity and impact on human disease. Nutrition and Aging. 2012;1(2):99-111. [DOI:10.3233/NUA-2012-0006]
36. dos Santos TC, Gomes TM, Pinto BAS, Camara AL, de Andrade Paes AM. Naturally occurring acetylcholinesterase inhibitors and their potential use for Alzheimer's disease therapy. Front Pharmacol. 2018;9. [DOI:10.3389/fphar.2018.01192]
37. Moran M, Mufson E, Gomez-Ramos P. Colocalization of cholinesterases with β amyloid protein in aged and Alzheimer's brains. Acta Neuropathologica. 1993;85(4):362-9. [DOI:10.1007/BF00334445]
38. Inestrosa NC, Alvarez A, Perez CA, et al. Acetylcholinesterase accelerates assembly of amyloid-beta-peptides into Alzheimer's fibrils: possible role of the peripheral site of the enzyme. Neuron. 1996;16(4):881-91. [DOI:10.1016/S0896-6273(00)80108-7]
39. Alvarez A, Alarcón R, Opazo C, et al. Stable complexes involving acetylcholinesterase and amyloid-β peptide change the biochemical properties of the enzyme and increase the neurotoxicity of Alzheimer's fibrils. J Neurosci. 1998;18(9):3213-23. [DOI:10.1523/JNEUROSCI.18-09-03213.1998]
40. Soodi M, Saeidnia S, Sharifzadeh M, et al. Satureja bachtiarica ameliorate beta-amyloid induced memory impairment, oxidative stress and cholinergic deficit in animal model of Alzheimer's disease. Metab Brain Dis. 2016;31(2):395-404. [DOI:10.1007/s11011-015-9773-y]
41. Sberna G, Sáez‐Valero J, Beyreuther K, Masters CL, Small DH. The amyloid β‐protein of Alzheimer's disease increases acetylcholinesterase expression by increasing intracellular calcium in embryonal carcinoma P19 cells. J Neurochem. 1997;69(3):1177-84. [DOI:10.1046/j.1471-4159.1997.69031177.x]
42. Härtl R, Gleinich A, Zimmermann M. Dramatic increase in readthrough acetylcholinesterase in a cellular model of oxidative stress. J Neurochem. 2011;116(6):1088-96. [DOI:10.1111/j.1471-4159.2010.07164.x]
43. Sepand MR, Soodi M, Hajimehdipoor H, Soleimani M, Sahraei E. Comparison of neuroprotective effects of Melissa officinalis total extract and its acidic and non-acidic fractions against A beta-Induced toxicity. Iran J Pharmaceut Res. 2013;12(2):415-23.

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