In vitro neuroprotective effects of allicin on Alzheimer’s disease model of neuroblastoma cell line

Abstract

Background/Aim: Alzheimer's disease is a progressive disorder that causes atrophy and neuronal death in the brain. Currently, there is not any effective therapy for Alzheimer's disease. The current research was designed to investigate the beneficial effects of allicin on Alzheimer’s disease in SHSY-5Y cells in vitro and elucidating the neuroprotective mechanism of allicin. Methods: Human neuroblastoma cell line (SH-SY5Y) was differentiated with retinoic acid to conduct the in vitro Alzheimer’s Disease model. Amyloid β1-42 protein was applied to the cells for 24 hours (2.5 µM) to induce cytotoxicity. Allicin was applied to the cell cultures in a wide spectrum dose (10 μM, 50 μM, 100 μM) to investigate neuroprotective effect against amyloid β for 24 hours. MTT and LDH analyses were performed to assess the cell viability. MDA and ROS concentrations and SOD activity were analyzed to determine the oxidative stress. Moreover, the effects of allicin on the caspase-3 expression in amyloid β induced neurotoxicity were determined by the RT-PCR analysis. Results: Amyloid β markedly decreased cell viability of SH-SY5Y in MTT analysis and elevated LDH levels. In contrast, in MTT analysis, the allicin markedly increased cell viability, indicating that allicin induces cell proliferation. Moreover, in LDH analysis, allicin treatment markedly decreased LDH release. Exposure to amyloid β markedly increased MDA and ROS levels, in comparison with the control. Moreover, amyloid β decreased activity of SOD in SH-SY5Y cells. Allicin markedly balanced out the amyloid β-induced MDA and ROS generation. In the same pathway, allicin increased activity of SOD in amyloid β -exposed SH-SY5Y cells. The caspase 3 expression was increased in amyloid β group in comparison to the control group and allicin markedly lowered the expression of caspase-3 levels. Conclusion: The beneficial effects of allicin on amyloid β -induced neurotoxicity on SH-SY5Y cells were reported for the first time in terms of cell viability, oxidative stress and apoptosis.

Keywords

• Allicin
• Alzheimer’s disease
• Antioxidant
• Apoptosis
• SH-SY5Y cell line

References

1. 1. Zhang L, Yu H, Zhao X, Lin X, Tan C, Cao G, et al. Neuroprotective effects of salidroside against beta-amyloid-induced oxidative stress in SH-SY5Y human neuroblastoma cells. Neurochem Int. 2010;57(5):547-55.
2. 1. Zhang L, Yu H, Zhao X, Lin X, Tan C, Cao G, et al. Neuroprotective effects of salidroside against beta-amyloid-induced oxidative stress in SH-SY5Y human neuroblastoma cells. Neurochem Int. 2010;57(5):547-55.
3. 2. Scheltens P, De Strooper B, Kivipelto M, Holstege H, Chetelat G, Teunissen CE, et al. Alzheimer's disease. Lancet. 2021;397(10284):1577-90.
4. 2. Scheltens P, De Strooper B, Kivipelto M, Holstege H, Chetelat G, Teunissen CE, et al. Alzheimer's disease. Lancet. 2021;397(10284):1577-90.
5. 3. Dubois B, Villain N, Frisoni GB, Rabinovici GD, Sabbagh M, Cappa S, et al. Clinical diagnosis of Alzheimer's disease: recommendations of the International Working Group. Lancet Neurol. 2021;20(6):484-96.
6. 3. Dubois B, Villain N, Frisoni GB, Rabinovici GD, Sabbagh M, Cappa S, et al. Clinical diagnosis of Alzheimer's disease: recommendations of the International Working Group. Lancet Neurol. 2021;20(6):484-96.
7. 4. Selkoe DJ. Translating cell biology into therapeutic advances in Alzheimer's disease. Nature. 1999;399(6738 Suppl):A23-31.
8. 4. Selkoe DJ. Translating cell biology into therapeutic advances in Alzheimer's disease. Nature. 1999;399(6738 Suppl):A23-31.

9. 5. Roher AE, Chaney MO, Kuo YM, Webster SD, Stine WB, Haverkamp LJ, et al. Morphology and toxicity of Abeta-(1-42) dimer derived from neuritic and vascular amyloid deposits of Alzheimer's disease. J Biol Chem. 1996;271(34):20631-5.
10. 5. Roher AE, Chaney MO, Kuo YM, Webster SD, Stine WB, Haverkamp LJ, et al. Morphology and toxicity of Abeta-(1-42) dimer derived from neuritic and vascular amyloid deposits of Alzheimer's disease. J Biol Chem. 1996;271(34):20631-5.
11. 6. Yun YJ, Park BH, Hou J, Oh JP, Han JH, Kim SC. Ginsenoside F1 Protects the Brain against Amyloid Beta-Induced Toxicity by Regulating IDE and NEP. Life (Basel). 2022;12(1).
12. 6. Yun YJ, Park BH, Hou J, Oh JP, Han JH, Kim SC. Ginsenoside F1 Protects the Brain against Amyloid Beta-Induced Toxicity by Regulating IDE and NEP. Life (Basel). 2022;12(1).
13. 7. Halliwell B. Oxidative stress and neurodegeneration: where are we now? J Neurochem. 2006;97(6):1634-58.
14. 7. Halliwell B. Oxidative stress and neurodegeneration: where are we now? J Neurochem. 2006;97(6):1634-58.
15. 8. Molina-Holgado F, Gaeta A, Francis PT, Williams RJ, Hider RC. Neuroprotective actions of deferiprone in cultured cortical neurones and SHSY-5Y cells. J Neurochem. 2008;105(6):2466-76.
16. 8. Molina-Holgado F, Gaeta A, Francis PT, Williams RJ, Hider RC. Neuroprotective actions of deferiprone in cultured cortical neurones and SHSY-5Y cells. J Neurochem. 2008;105(6):2466-76.
17. 9. Guo T, Zhang D, Zeng Y, Huang TY, Xu H, Zhao Y. Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer's disease. Mol Neurodegener. 2020;15(1):40.
18. 9. Guo T, Zhang D, Zeng Y, Huang TY, Xu H, Zhao Y. Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer's disease. Mol Neurodegener. 2020;15(1):40.
19. 10. Yang Y, Zhang Z. Microglia and Wnt Pathways: Prospects for Inflammation in Alzheimer's Disease. Front Aging Neurosci. 2020;12:110.
20. 10. Yang Y, Zhang Z. Microglia and Wnt Pathways: Prospects for Inflammation in Alzheimer's Disease. Front Aging Neurosci. 2020;12:110.
21. 11. Zhu JW, Chen T, Guan J, Liu WB, Liu J. Neuroprotective effects of allicin on spinal cord ischemia-reperfusion injury via improvement of mitochondrial function in rabbits. Neurochem Int. 2012;61(5):640-8.
22. 11. Zhu JW, Chen T, Guan J, Liu WB, Liu J. Neuroprotective effects of allicin on spinal cord ischemia-reperfusion injury via improvement of mitochondrial function in rabbits. Neurochem Int. 2012;61(5):640-8.
23. 12. Li XH, Li CY, Xiang ZG, Zhong F, Chen ZY, Lu JM. Allicin can reduce neuronal death and ameliorate the spatial memory impairment in Alzheimer's disease models. Neurosciences (Riyadh). 2010;15(4):237-43.
24. 12. Li XH, Li CY, Xiang ZG, Zhong F, Chen ZY, Lu JM. Allicin can reduce neuronal death and ameliorate the spatial memory impairment in Alzheimer's disease models. Neurosciences (Riyadh). 2010;15(4):237-43.
25. 13. Kong X, Gong S, Su L, Li C, Kong Y. Neuroprotective effects of allicin on ischemia-reperfusion brain injury. Oncotarget. 2017;8(61):104492-507.
26. 13. Kong X, Gong S, Su L, Li C, Kong Y. Neuroprotective effects of allicin on ischemia-reperfusion brain injury. Oncotarget. 2017;8(61):104492-507.
27. 14. Liu H, Mao P, Wang J, Wang T, Xie CH. Allicin Protects PC12 Cells Against 6-OHDA-Induced Oxidative Stress and Mitochondrial Dysfunction via Regulating Mitochondrial Dynamics. Cell Physiol Biochem. 2015;36(3):966-79.
28. 14. Liu H, Mao P, Wang J, Wang T, Xie CH. Allicin Protects PC12 Cells Against 6-OHDA-Induced Oxidative Stress and Mitochondrial Dysfunction via Regulating Mitochondrial Dynamics. Cell Physiol Biochem. 2015;36(3):966-79.
29. 15. Ferah Okkay I, Okkay U, Bayram C, Cicek B, Sezen S, Aydin IC, et al. Bromelain protects against cisplatin-induced ocular toxicity through mitigating oxidative stress and inflammation. Drug Chem Toxicol. 2021:1-8.
30. 15. Ferah Okkay I, Okkay U, Bayram C, Cicek B, Sezen S, Aydin IC, et al. Bromelain protects against cisplatin-induced ocular toxicity through mitigating oxidative stress and inflammation. Drug Chem Toxicol. 2021:1-8.
31. 16. Bush AI. Metal complexing agents as therapies for Alzheimer's disease. Neurobiol Aging. 2002;23(6):1031-8.
32. 16. Bush AI. Metal complexing agents as therapies for Alzheimer's disease. Neurobiol Aging. 2002;23(6):1031-8.
33. 17. Guo Y, Liu H, Chen Y, Yan W. The effect of allicin on cell proliferation and apoptosis compared to blank control and cis-platinum in oral tongue squamous cell carcinoma. Onco Targets Ther. 2020;13:13183-89.
34. 17. Guo Y, Liu H, Chen Y, Yan W. The effect of allicin on cell proliferation and apoptosis compared to blank control and cis-platinum in oral tongue squamous cell carcinoma. Onco Targets Ther. 2020;13:13183-89.
35. 18. Xiang Q, Li XH, Yang B, Fang XX, Jia J, Ren J, et al. Allicin attenuates tunicamycin-induced cognitive deficits in rats via its synaptic plasticity regulatory activity. Iran J Basic Med Sci. 2017;20(6):676-82.
36. 18. Xiang Q, Li XH, Yang B, Fang XX, Jia J, Ren J, et al. Allicin attenuates tunicamycin-induced cognitive deficits in rats via its synaptic plasticity regulatory activity. Iran J Basic Med Sci. 2017;20(6):676-82.
37. 19. Zhang H, Wang P, Xue Y, Liu L, Li Z, Liu Y. Allicin ameliorates cognitive impairment in APP/PS1 mice via Suppressing oxidative stress by Blocking JNK Signaling Pathways. Tissue Cell. 2018;50:89-95.
38. 19. Zhang H, Wang P, Xue Y, Liu L, Li Z, Liu Y. Allicin ameliorates cognitive impairment in APP/PS1 mice via Suppressing oxidative stress by Blocking JNK Signaling Pathways. Tissue Cell. 2018;50:89-95.
39. 20. Mocayar Maron FJ, Camargo AB, Manucha W. Allicin pharmacology: Common molecular mechanisms against neuroinflammation and cardiovascular diseases. Life Sci. 2020;249:117513.
40. 20. Mocayar Maron FJ, Camargo AB, Manucha W. Allicin pharmacology: Common molecular mechanisms against neuroinflammation and cardiovascular diseases. Life Sci. 2020;249:117513.
41. 21. Obulesu M, Lakshmi MJ. Apoptosis in Alzheimer's disease: an understanding of the physiology, pathology and therapeutic avenues. Neurochem Res. 2014;39(12):2301-12.
42. 21. Obulesu M, Lakshmi MJ. Apoptosis in Alzheimer's disease: an understanding of the physiology, pathology and therapeutic avenues. Neurochem Res. 2014;39(12):2301-12.
43. 22. Kroemer G, Galluzzi L, Brenner C. Mitochondrial membrane permeabilization in cell death. Physiol Rev. 2007;87(1):99-163.
44. 22. Kroemer G, Galluzzi L, Brenner C. Mitochondrial membrane permeabilization in cell death. Physiol Rev. 2007;87(1):99-163.
45. 23. Hu L, Chen L, Yang G, Li L, Sun H, Chang Y, et al. HBx sensitizes cells to oxidative stress-induced apoptosis by accelerating the loss of Mcl-1 protein via caspase-3 cascade. Mol Cancer. 2011;10:43.
46. 23. Hu L, Chen L, Yang G, Li L, Sun H, Chang Y, et al. HBx sensitizes cells to oxidative stress-induced apoptosis by accelerating the loss of Mcl-1 protein via caspase-3 cascade. Mol Cancer. 2011;10:43.
47. 24. Zhong D, Wang H, Liu M, Li X, Huang M, Zhou H, et al. Ganoderma lucidum polysaccharide peptide prevents renal ischemia reperfusion injury via counteracting oxidative stress. Sci Rep. 2015;5:16910.
48. 24. Zhong D, Wang H, Liu M, Li X, Huang M, Zhou H, et al. Ganoderma lucidum polysaccharide peptide prevents renal ischemia reperfusion injury via counteracting oxidative stress. Sci Rep. 2015;5:16910.