Volume 24, Issue 4 (7-2020)                   IBJ 2020, 24(4): 243-250 | Back to browse issues page


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Azizi Z, Salimi M, Amanzadeh A, Majelssi N, Naghdi N. Carvacrol and Thymol Attenuate Cytotoxicity Induced by Amyloid β25-35 Via Activating Protein Kinase C and Inhibiting Oxidative Stress in PC12 Cells. IBJ 2020; 24 (4) :243-250
URL: http://ibj.pasteur.ac.ir/article-1-3022-en.html
Abstract:  
Background: Our previous findings indicated that carvacrol and thymol alleviate cognitive impairments caused by Aβ in rodent models of Alzheimer's disease (AD). In this study, the neuroprotective effects of carvacrol and thymol against Aβ25-35-induced cytotoxicity were evaluated, and the potential mechanisms were determined. Methods: PC12 cells were pretreated with Aβ25-35 for 2 h, followed by incubation with carvacrol or thymol for additional 48 h. Cell viability was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. A flurospectrophotometer was employed to observe the intracellular reactive oxygen species (ROS) production. Protein kinase C (PKC) activity was analyzed using ELISA. Results: Our results indicated that carvacrol and thymol could significantly protect PC12 cells against Aβ25-35-induced cytotoxicity. Furthermore, Aβ25-35 could induce intracellular ROS production, while carvacrol and thymol could reverse this effect. Moreover, our findings showed that carvacrol and thymol elevate PKC activity similar to Bryostatin-1, as a PKC activator. Conclusion: This study provided the evidence regarding the protective effects of carvacrol and thymol against Aβ25–35-induced cytotoxicity in PC12 cells. The results suggested that the neuroprotective effects of these compounds against Aβ25-35 might be through attenuating oxidative damage and increasing the activity of PKC as a memory-related protein. Thus, carvacrol and thymol were found to have therapeutic potential in preventing or modulating AD.
Type of Study: Full Length/Original Article | Subject: Related Fields

References
1. Selkoe DJ. Alzheimer's disease results from the cerebral accumulation and cytotoxicity of amyloid beta-protein. Journal of Alzheimer's disease 2001; 3(1): 75-80. [DOI:10.3233/JAD-2001-3111]
2. Habtemariam S. Iridoids and other monoterpenes in the Alzheimer's brain: recent development and future prospects. Molecules 2018; 23(1): pii: E117. [DOI:10.3390/molecules23010117]
3. Duyckaerts C, Delatour B, Potier MC. Classification and basic pathology of Alzheimer disease. Acta neuropathologica 2009; 118(1): 5-36. [DOI:10.1007/s00401-009-0532-1]
4. Haass C, Koo EH, Mellon A, Hung AY, Selkoe DJ. Targeting of cell-surface beta-amyloid precursor protein to lysosomes: alternative processing into amyloid-bearing fragments. Nature 1992; 357(6378): 500-503. [DOI:10.1038/357500a0]
5. Selkoe DJ. The cell biology of beta-amyloid precursor protein and presenilin in Alzheimer's disease. Trends in cell biology 1998; 8(11): 447-453. [DOI:10.1016/S0962-8924(98)01363-4]
6. Etcheberrigaray R, Tan M, Dewachter I, Kuipéri C, Van der Auwera I, Wera S, Qiao L, Bank B, Nelson TJ, Kozikowski AP, Van Leuven F, Alkon DL. Therapeutic effects of PKC activators in Alzheimer's disease transgenic mice. Proceedings of the national academy of sciences of the United States of America 2004; 101(30): 11141-11146. [DOI:10.1073/pnas.0403921101]
7. Sun MK, Alkon DL. Pharmacology of protein kinase C activators: cognition-enhancing and anti dementic therapeutics. Pharmacology and therapeutics 2010; 127(1): 66-77. [DOI:10.1016/j.pharmthera.2010.03.001]
8. Leuner K, Schütt T, Kurz CH, Eckert SH, Schiller C, Occhipinti A, Mai S, Jendrach M, Eckert GP, Kruse SE, Palmiter RD, Brandt U, Dröse S, Wittig I, Willem M, Haass C, Reichert AS, Müller WE. Mitochondrion-derived reactive oxygen species lead to enhanced amyloid beta formation. Antioxidants and redox signaling 2012; 16(12); 1421-1433. [DOI:10.1089/ars.2011.4173]
9. Swomley AM, Butterfield DA. Oxidative stress in Alzheimer's disease and mild cognitive impairment: evidence from human data provided by redox proteomics. Archives of toxicology 2015; 89(10): 1669-1680. [DOI:10.1007/s00204-015-1556-z]
10. Behl C, Moosmann B. Oxidative nerve cell death in Alzheimer's disease and stroke: antioxidants as neuroprotective compounds. Biological chemistry 2002; 383(3-4): 521-536. [DOI:10.1515/BC.2002.053]
11. Aliev G, Obrenovich ME, Reddy VP, Shenk JC, Moreira PI, Nunomura A, Zhu X, Smith MA, Perry G. Antioxidant therapy in Alzheimer's disease: theory and practice. Mini-reviews in medicinal chemistry 2008; 8(13): 1395-1406. [DOI:10.2174/138955708786369582]
12. Galimberti D, Scarpini E. Disease-modifying treatments for Alzheimer's disease. Therapeutic advances in neurological disorders 2011; 4(4): 203-216. [DOI:10.1177/1756285611404470]
13. Essa MM, Vijayan K, Castellano-Gonzalez G, Memon MA, Braidy N, Guillemin GJ. Neuroprotective effect of natural products against Alzheimer's disease. Neurochemical research 2012; 37(9): 1829-1842. [DOI:10.1007/s11064-012-0799-9]
14. Kim MH, Kim SH, Yang WM. Mechanisms of action of phytochemicals from medicinal herbs in the treatment of Alzheimer's disease. Planta medica 2014; 80(15): 1249-1258. [DOI:10.1055/s-0034-1383038]
15. Tewari D, Stankiewicz AM, Mocan A, Sah, AN, Tzvetkov NT, Huminiecki L, Horbańczuk JO, Atanasov AG. Ethnopharmacological approaches for dementia therapy and significance of natural products and herbal drugs. Frontiers in aging neuroscience 2018; 10: 3. [DOI:10.3389/fnagi.2018.00003]
16. Lakey-Beitia J, Berrocal R, Rao KS, Durant AA. Polyphenols as therapeutic molecules in Alzheimer's disease through modulating amyloid pathways. Molecular neurobiology 2015; 51(2): 466-479. [DOI:10.1007/s12035-014-8722-9]
17. Syarifah-Noratiqah S, Naina-Mohamed I, Zulfarina MS, Qodriyah HM. Natural polyphenols in the treatment of Alzheimer's disease. Current drug targets 2018; 19(8): 927-937. [DOI:10.2174/1389450118666170328122527]
18. Sawikr Y, Yarla NS, Peluso I, Kamal MA, Aliev G, Bishayee A. Neuroinflammation in Alzheimer's disease: The preventive and therapeutic potential of polyphenolic nutraceuticals. Advances in protein chemistry and structural biology 2017; 108: 33-57. [DOI:10.1016/bs.apcsb.2017.02.001]
19. Baser KH. Biological and pharmacological activities of carvacrol and carvacrol bearing essential oils. Current pharmaceutical design 2008; 14(29): 3106-3119. [DOI:10.2174/138161208786404227]
20. Wei HK, Xue HX, Zhou ZX, Peng J. A carvacrol-thymol blend decreased intestinal oxidative stress and influenced selected microbes without changing the messenger RNA levels of tight junction proteins in jejunal mucosa of weaning piglets. Animal 2017; 11(2): 193-201. [DOI:10.1017/S1751731116001397]
21. El-Sayed el-SM, Mansour AM, Abdul-Hameed MS. Thymol and carvacrol prevent doxorubicin-induced cardiotoxicity by abrogation of oxidative stress, inflammation, and apoptosis in rats. Journal of biochemical and molecular toxicology 2016; 30(1): 37-44. [DOI:10.1002/jbt.21740]
22. Azizi Z, Ebrahimi S, Saadatfar E, Kamalinejad M, Majlessi N. Cognitive-enhancing activity of thymol and carvacrol in two rat models of dementia. Behavioural pharmacology 2012; 23(3): 241-249. [DOI:10.1097/FBP.0b013e3283534301]
23. Liu Y, Peterson DA, Kimura H, Schubert D. Mechanism of cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) reduction. Journal of neurochemistry 1997; 69(2): 581-593. [DOI:10.1046/j.1471-4159.1997.69020581.x]
24. LeBel CP, Ischiropoulos H, Bondy SC. Evaluation of the probe 2',7'-dichlorofluorescin as an indicator of reactive oxygen species formation and oxidative stress. Chemical research in toxicology 1992; 5(2): 227-231. [DOI:10.1021/tx00026a012]
25. Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 2002; 297(5580): 353-356. [DOI:10.1126/science.1072994]
26. Parvez MK. Natural or plant products for the treatment of neurological disorders: Current knowledge. Current drug metabolism 2018; 19(5): 424-428. [DOI:10.2174/1389200218666170710190249]
27. Arigesavan K, Sudhandiran G. Carvacrol exhibits anti-oxidant and anti-inflammatory effects against 1, 2-dimethyl hydrazine plus dextran sodium sulfate induced inflammation associated carcinogenicity in the colon of Fischer 344 rats. Biochemical and biophysical research communications 2015; 461(2): 314-320. [DOI:10.1016/j.bbrc.2015.04.030]
28. FangFang Li H, Qin T, Li M, Ma S. Thymol improves high-fat diet-induced cognitive deficits in mice via ameliorating brain insulin resistance and up regulating NRF2/HO-1 pathway. Metabolic brain disease 2017; 32(2): 385-393. [DOI:10.1007/s11011-016-9921-z]
29. Wang P, Luo Q, Qiao H, Ding H, Cao Y, Yu J, Liu R, Zhang Q, Zhu H, Qu L. The Neuroprotective effects of carvacrol on ethanol-induced hippocampal neurons impairment via the antioxidative and anti apoptotic pathways. Oxidative medicine and cellular longevity 2017; 2017: 4079425. [DOI:10.1155/2017/4079425]
30. Greene LA, Tischler AS. Establishment of a noradrenergic clonal line of rat adrenal pheochromo- cytoma cells which respond to nerve growth factor. Proceedings of the national academy of sciences of the United States of America 1976; 73(7): 2424-2428. [DOI:10.1073/pnas.73.7.2424]
31. Yankner BA, Duffy LK, Kirschner DA. Neurotrophic and neurotoxic effects of amyloid beta protein: reversal by tachykinin neuropeptides. Science 1990; 250(4978): 279-282. [DOI:10.1126/science.2218531]
32. Shearman MS, Ragan CI, Iversen LL. Inhibition of PC12 cell redox activity is a specific, early indicator of the mechanism of beta-amyloid-mediated cell death. Proceedings of the national academy of sciences of the United States of America 1994; 91(4): 1470-1474. [DOI:10.1073/pnas.91.4.1470]
33. Reddy VP, Zhu X, Perry G, Smith MA. Oxidative stress in diabetes and Alzheimer's disease. Journal of Alzheimers disease 2009; 16(4): 763-774. [DOI:10.3233/JAD-2009-1013]
34. Bennett SP, Boyd TD, Norden M, Padmanabhan J, Neame P, Wefes I, Potter H. A novel technique for simultaneous bilateral brain infusions in a mouse model of neurodegenerative disease. Journal of neuroscience methods 2009; 184(2): 320-326. [DOI:10.1016/j.jneumeth.2009.08.021]
35. Kaminsky YG, Marlatt MW, Smith MA, Kosenko EA. Sub cellular and metabolic examination of amyloid-beta peptides in Alzheimer disease pathogenesis: evidence for Abeta(25-35). Experimental neurology 2010; 221(1): 26-37. [DOI:10.1016/j.expneurol.2009.09.005]
36. Asadbegi M, Komaki A, Salehi I, Yaghmaei P, Ebrahim-Habibi A, Shahidi S, Sarihi A, Soleimani Asl S, Golipoor Z. Effects of thymol on amyloid-β-induced impairments in hippocampal synaptic plasticity in rats fed a high-fat diet. Brain research bulletin 2018; 137: 338-350. [DOI:10.1016/j.brainresbull.2018.01.008]
37. Majewski H, Iannazzo L. Protein kinase C: a physiological mediator of enhanced transmitter output. Progress in neurobiology 1998; 55(5): 463-475. [DOI:10.1016/S0301-0082(98)00017-3]
38. Cole G, Dobkins KR, Hansen LA, Terry RD, Saitoh T. Decreased levels of protein kinase C in Alzheimer brain. Brain research 1988; 452(1-2): 165-174. [DOI:10.1016/0006-8993(88)90021-2]
39. Wang HY, Pisano MR, Friedman E. Attenuated protein kinase C activity and translocation in Alzheimer's disease brain. Neurobiology aging 1994; 15(3): 293-298. [DOI:10.1016/0197-4580(94)90023-X]
40. Sun MK, Alkon DL. The "memory kinases": roles of PKC isoforms in signal processing and memory formation. Progress in molecular biology and translational science 2014; 122: 31-59. [DOI:10.1016/B978-0-12-420170-5.00002-7]
41. Chen Y, Ba L, Huang, W, Liu Y, Pan H, Mingyao E, Shi P, Wang Y, Li S, Qi H, Sun H, Cao Y. Role of carvacrol in cardioprotection against myocardial ischemia/reperfusion injury in rats through activation of MAPK/ERK and Akt/eNOS signaling pathways. European journal of pharmacology 2017; 796: 90-100. [DOI:10.1016/j.ejphar.2016.11.053]
42. Bolognesi ML, Rosini M, Andrisano V, Bartolini M, Minarini A, Tumiatti V, Melchiorre C. MTDL design strategy in the context of Alzheimer's disease: from lipocrine to memoquin and beyond. Current pharmaceutical design 2009; 15(6): 601-613. [DOI:10.2174/138161209787315585]
43. Zhang HY. One-compound-multiple-targets strategy to combat Alzheimer's disease. FEBS letters 2005; 579(24): 5260-5264. [DOI:10.1016/j.febslet.2005.09.006]
44. Ji ZH, Liu C, Zhao H, Yu XY. Neuroprotective effect of Biatractylenolide against memory impairment in D-Galactose-induced aging mice. Journal of molecular neuroscience 2015; 55(3): 678-683. [DOI:10.1007/s12031-014-0407-3]
45. Rebai O, Belkhir M, Sanchez-Gomez MV, Matute C, Fattouch S, Amri M. Differential molecular targets for neuroprotective effect of chlorogenic acid and its related compounds against glutamate induced excitotoxicity and oxidative stress in rat cortical neurons. Neurochemical research 2017; 42(12): 3559-3572. [DOI:10.1007/s11064-017-2403-9]
46. Levites Y, Amit T, Youdim MB, Mandel S. Involvement of protein kinase C activation and cell survival/ cell cycle genes in green tea polyphenol (-)-epigallocatechin 3-gallate neuroprotective action. Journal of biological chemistry 2002; 277(34): 30574-30580. [DOI:10.1074/jbc.M202832200]

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