Journal of Applied Biological Chemistry

The Korean Society for Applied Biological Chemistry (한국응용생명화학회)
권호 표지
DOI QR코드

DOI QR Code

Neuroprotective effects of Paeonia lactiflora and its active compound paeoniflorin against Aβ25-35-induced neurotoxicity in SH-SY5Y cells

  • Nam, Mi Na (Department of Food Science and Nutrition & Kimchi Research Institute, Pusan National University) ;
  • Kim, Ji-Hyun (Department of Food Science and Nutrition & Kimchi Research Institute, Pusan National University) ;
  • Lee, Ah Young (Department of Food Science, Gyeongnam National University of Science and Technology) ;
  • Cho, Eun Ju (Department of Food Science and Nutrition & Kimchi Research Institute, Pusan National University)
  • Received : 2021.02.17
  • Accepted : 2021.03.02
  • Published : 2021.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

Excessive accumulation of the amyloid beta (Aβ) peptide has been implicated in the pathogenesis of Alzheimer's disease (AD). Paeonia lactiflora (PL) has been used in treatments of several conditions such as inflammation, arthritis, and cognitive impairment. The purpose of this study was to investigate the neuroprotective effect and mechanisms of PL and its active compound, paeoniflorin (PF), on Aβ25-35-induced neurotoxicity in SH-SY5Y cells. We evaluated cell viability, lactate dehydrogenase (LDH) release and reactive oxygen species (ROS) production. Furthermore, underlying mechanism of PL and PF on the regulation of amyloidogenic pathway was analyzed by Western blotting. In our results, Aβ25-35-induced neuronal cell loss was observed, whereas treatment with PL (10, 50, and 100 ㎍/mL) and PF (1, 5, and 10 ㎍/mL) significantly elevated the cell viability, and decreased LDH release and ROS production. In addition, exposure of SH-SY5Y cells to Aβ25-35 significantly increased the protein levels of amyloid precursor protein (APP)-C-terminal fragment β, β-site APP-cleaving enzyme, and presenilin-1 and -2. However, treatment with PL and PF inhibited the amyloidogenic pathway via the down-regulation of those protein expressions. Taken together, our results indicate that PL, and its active compound PF, could protect SH-SY5Y cells against Aβ25-35-induced cell neurotoxicity by attenuating LDH release and ROS production, and these effects may be attributed to regulation of amyloidogenic pathway-related protein expression. In conclusion, PL and PF could be a potential to prevent neurodegenerative disorders such as AD.

Keywords

Acknowledgement

This work was supported by the research invigoration program of 2020 Gyeongnam National University of Science and Technology.

References

  1. Piaceri I, Rinnoci V, Bagnoli S, Failli Y, Sorbi S (2012) Mitochondria and Alzheimer's disease. J Neurol Sci 322: 31-34. doi: 10.1016/j.jns.2012.05.033
  2. Selkoe DJ, Schenk D (2003) Alzheimer's disease: molecular understanding predicts amyloid-based therapeutics. Annu Rev Pharmacol Toxicol 43: 545-584. doi: 10.1146/annurev.pharmtox.43.100901.140248
  3. Qiu C, Kivipelto M, von Strauss E (2009) Epidemiology of Alzheimer's disease: occurrence, determinants, and strategies toward intervention. Dialogues Clin Neurosci 11: 111-128. doi: 10.31887/DCNS.2009.11.2/cqiu
  4. Prince M, Wimo A, Guerchet M, Ali GC, Wu YT, Prina M (2015) World Alzheimer Report: The Global Impact of Dementia. Alzheimer's Disease International (ADI), London
  5. Hansen RA, Gartlehner G, Webb AP, Morgan LC, Moore CG, Jonas DE (2008) Efficacy and safety of donepezil, galantamine, and rivastigmine for the treatment of Alzheimer's disease: a systematic review and metaanalysis. Clin Interv Aging 3: 211-225
  6. Beal MF (1996) Mitochondria, free radicals, and neurodegeneration. Curr Opin Neurobiology 6: 661-666. doi: 10.1016/s0959-4388(96)80100-0
  7. Markesbery WR (1997) Oxidative stress hypothesis in Alzheimer's disease. Free Radic Biol Med 23: 134-147. doi: 10.1016/s0891-5849(96)00629-6
  8. Holmes C, Cunningham C, Zotova E, Woolford J, Dean C, Kerr S, Culliford D, Perry VH (2009) Systemic inflammation and disease progression in Alzheimer disease. Neurology 73: 768-774. doi: 10.1212/WNL.0b013e3181b6bb95
  9. Pettmann B, Henderson CE (1998) Neuronal cell death. Neuron 20: 633-647 https://doi.org/10.1016/S0896-6273(00)81004-1
  10. Citron M (2010) Alzheimer's disease: strategies for disease modification. Nat Rev Drug Discov 9: 387-398. doi: 10.1038/nrd2896
  11. Blennow K, de Leon MJ, Zetterberg H (2006) Alzheimer's disease. Lancet 368: 387-403 https://doi.org/10.1016/S0140-6736(06)69113-7
  12. Portelius E, Gustavsson MK, Zetterberg H, Andreasson U, Blennow K (2012) Evaluation of the performance of novel Aβ isoforms as theragnostic markers in Alzheimer's disease: from the cell to the patient. Neurodegener Dis 10: 138-140. doi: 10.1159/000334537
  13. Luo Y, Sunderland T, Roth GS, Wolozin B (1996) Physiological levels of beta-amyloid peptide promote PC12 cell proliferation. Neurosci Lett 217: 125-128 https://doi.org/10.1016/0304-3940(96)13087-1
  14. Moya KL, Benowitz LI, Schneider GE, Allinquant B (1994) The amyloid precursor protein is developmentally regulated and correlated with synaptogenesis. Dev Biol 161: 597-603. doi: 10.1006/dbio.1994.1055
  15. Mileusnic R, Lancashire CL, Johnston AN, Rose SP (2000) APP is required during an early phase of memory formation. Eur J Neurosci 12: 4487-4495 https://doi.org/10.1111/j.1460-9568.2000.01344.x
  16. Butterfield DA, Lauderback CM (2002) Lipid peroxidation and protein oxidation in Alzheimer's disease brain: potential causes and consequences involving amyloid beta-peptide-associated free radical oxidative stress. Free Radic Biol Med 32: 1050-1060. doi: 10.1016/s0891-5849(02)00794-3
  17. Jellinger KA (2006) Challenges in neuronal apoptosis. Curr Alzheimer Res 3: 377-391. doi: 10.2174/156720506778249434
  18. Zhu L, Wei W, Zheng YQ, Jia XY (2005) Effects and mechanisms of total glucosides of paeony on joint damage in rat collagen-induced arthritis. Inflamm Res 54: 211-220. doi: 10.1007/s00011-005-1345-x
  19. Koo YK, Kim JM, Koo JY, Kang SS, Bae KH, Kim YS, Chung JH, Yun-Choi HS (2010) Platelet anti-aggregatory and blood ant-coagulant effects of compounds isolated from Paeonia lactiflora and Paeonia suffruticosa. Pharmazie 65: 624-628
  20. He DY, Dai SM (2011) Anti-inflammatory and immunomodulatory effects of Paeonia lactiflora Pall., a traditional Chinese herbal medicine. Front Pharmacol 25: 10. doi: 10.3389/fphar.2011.00010
  21. Zhang W, Dai SM (2012) Mechanisms involved in the therapeutic effects of Paeonia lactiflora Pallas in rheumatoid arthritis. Int Immunopharmacol 14: 27-31. doi: 10.1016/j.intimp.2012.06.001
  22. Lan Z, Chen L, Fu Q, Ji W, Wang S, Liang Z, Qu R, Kong L, Ma S (2013) Paeoniflorin attenuates amyloid-beta peptide-induced neurotoxicity by ameliorating oxidative stress and regulating the NGF-mediated signaling in rats. Brain Res 1498: 9-19. doi: 10.1016/j.brainres.2012.12.040
  23. Wankun X, Wenzhen Y, Min Z, Weiyan Z, Huan C, Wei D, Xiaoxin L (2011) Protective effect of paeoniflorin against oxidative stress in human retinal pigment epithelium in vitro. Mol Vis 17: 3512-3522
  24. Zhang LL, Wei W, Wang NP, Wang QT, Chen JY, Chen Y, Wu H, Hui XY (2008) Paeoniflorin suppresses inflammatory mediator production and regulates G protein-coupled signaling in fibroblast-like synoviocytes from collagen induced arthritic rats. Inflamm Res 57: 388-395. doi: 10.1007/s00011-007-7240-x
  25. Liu HQ, Zhang WY, Luo XT, Ye Y, Zhu XZ (2006) Paeoniflorin attenuates neuroinflammation and dopaminergic neurodegeneration in the MPTP model of Parkinson's disease by activation of adenosine A1 receptor. Br J Pharmacol 148: 314-325. doi: 10.1038/sj.bjp.0706732
  26. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65: 55-63. doi: 10.1016/0022-1759(83)90303-4
  27. Racher AJ, Looby D, Griffiths JB (1990) Use of lactate dehydrogenase release to assess changes in culture viability. Cytotechnology 3: 301-307. doi: 10.1007/BF00365494
  28. Cathcart R, Schwiers E, Ames BN (1983) Detection of picomole levels of hydroperoxides using a fluorescent dichlorofluorescein assay. Anal Biochem 134: 111-116. doi: 10.1016/0003-2697(83)90270-1
  29. Price DL, Sisodia SS, Gandy SE (1995) Amyloid beta amyloidosis in Alzheimer's disease. Curr Opin Neurol 8: 268-274. doi: 10.1097/00019052-199508000-00004
  30. Shanker GM, Walsh DM (2009) Alzheimer's disease: synaptic dysfunction and Aβ. Mol Neurodegener 4: 48. doi: 10.1186/1750-1326-4-48
  31. Selkoe DJ (1998) The cell biology of β-amyloid precursor protein and presenilin in Alzheimer's disease. Trends Cell Biol 8: 447-453. doi: 10.1016/s0962-8924(98)01363-4
  32. Loo DT, Copani A, Pike CJ, Whittemore ER, Walencewicz AJ, Cotman CW (1993) Apoptosis is induced by β-amyloid in cultured central nervous system neurons. Proc Natl Acd Sci USA 90: 7951-7955. doi: 10.1073/pnas.90.17.7951
  33. Zhang X, Wan G, Li X (2001) A study on the chemical constituents of Paeonia lactiflora Pall. Shengyang Yao Ke Da Xue Xue Bao 18: 30-32 [in Chinese]
  34. Deng LJ, Lei YH, Chiu TF, Qi M, Gan H, Zhang G, Peng ZD, Zhang DM, Chen YF, Chen JX (2019) The anticancer effects of paeoniflorin and its underlying mechanisms. Nat Prod Commun 14: 1-8. doi: 10.1177/1934578X19876409
  35. Jian ZY, Yu JB, Wang WQ (2010) RP-HPLC determination of main chemical components in different parts and different harvest periods of Paeonia lactiflora. Yao Xue Xue Bao 45: 489-493 [in Chinese]
  36. Li X, De Sarno P, Song L, Beckman JS, Jope RS (1998) Peroxynitrite modulates tyrosine phosphorylation phosphoinositide signalling in human neuroblastoma SH-SY5Y cells: attenuated effects in human 1321N1 astrocytoma cells. Biochem J 331: 599-606. doi: 10.1042/bj3310599
  37. Yamamoto T, Maruyama W, Kato Y, Yi H, Shamoto-Nagai M, Tanaka M, Sato Y, Naoi M (2002) Selective nitration of mitochondrial complex I by peroxynitrite: involvement in mitochondria dysfunction cell death of dopaminergic SH-SY5Y cells. J Neural Transm 109: 1-13. doi: 10.1007/s702-002-8232-1
  38. Preston JE, Hipkiss AR, Himsworth DT, Romero IA, Abbott JN (1998) Toxic effects of β-amyloid (25-35) on immortalised rat brain endothelial cell: protection by carnosine, homocarnosine and β-alanine. Neurosci Lett 242: 105-108. doi: 10.1016/s0304-3940(98)00058-5
  39. Butterfield DA, Drake J, Pocernich C, Castegna A (2001) Evidence of oxidative damage in Alzheimer's disease brain: central role for amyloid β-peptide. Trends Mol Med 7: 548-554. doi: 10.1016/s1471-4914(01)02173-6
  40. Xiao X, Zhang H, Tang X (2002) Huperzine A attenuates amyloid betapeptide fragment 25-35-induced apoptosis in rat cortical neurons via inhibiting reactive oxygen species formation and caspase-3 activation. J Neurosci Res 67: 30-36. doi: 10.1002/jnr.10075
  41. Zheng Q, Li L, Jin Y Chen Z, Duan L, Cao M, Ma M, Wu Z (2019) A network pharmacology approach to reveal the underlying mechanisms of Paeonia lactiflora Pall. On the treatment of Alzheimer's disease. Evid Based Complement Alternat Med Article ID: 8706589. doi: 10.1155/2019/8706589
  42. Kim SH, Lee MK, Lee KY, Sung SH, Kim J, Kim YC (2009) Chemical constituents isolated from Paeonia lactiflora roots and their neuroprotective activity against oxidative stress in vitro. J Enzyme Inhib Med Chem 24: 1138-1140. doi: 10.1080/14756360802667977
  43. Li CR, Zhou Z, Zhu D, Sun YN, Dai JM, Wang SQ (2007) Protective effect of paeoniflorin on irradiation-induced cell damage involved in modulation of reactive oxygen species and the mitogen-activated protein kinases. Int J Biochem Cell Biol 39: 426-438. doi: 10.1016/j.biocel.2006.09.011
  44. Fan X, Wu J, Yang H, Yan L, Wang S (2018) Paeoniflorin blocks the proliferation of vascular smooth muscle cells induced by platelet-derived growth factor-BB through ROS mediated ERK1/2 and p38 signaling pathways. Mol Med Rep 17: 1676-1682. doi: 10.3892/mmr.2017.8093
  45. Wankun X, Wenzhen Y, Min Z, Weiyan Z, Huan C, Wei D, Xiaoxin L (2011) Protective effect of paeoniflorin against oxidative stress in human retinal pigment epithelium in vitro. Mol Vis 17: 3512-3522
  46. O'Brien RJ, Wong PC (2011) Amyloid precursor protein processing and Alzheimer's disease. Annu Rev Neurosci 34: 185-204. doi: 10.1146/annurev-neuro-061010-113613
  47. Vassar R, Kandalepas PC (2011) The β-secretase enzyme BACE1 as a therapeutic target for Alzheimer's disease. Alzheimers Res Ther 3: 20. doi: 10.1186/alzrt82
  48. Gandy S (2005) The role of cerebral amyloid β accumulation in common forms of Alzheimer disease. J Clin Invest 115: 1121-1129. doi: 10.1172/JCI25100
  49. Li T, Wen H, Brayton C, Laird FM, Ma G, Peng S, Plascanica L, Wu TC, Crain BJ, Price DL, Eberhart CG, Wong PC (2007) Moderate reduction of gamma-secretase attenuates amyloid burden and limits mechanism-based liabilities. J Neurosci 27: 10849-10859. doi: 10.1523/JNEUROSCI.2152-07.2007
  50. Chakrabarti S, Sinha M, G. Thakurta I, Banerjee P, Chattopadhyay M (2013) Oxidative stress and amyloid beta toxicity in Alzheimer's disease: Intervention in a complex relationship by antioxidants. Curr Med Chem 20: 4648-4664. doi: 10.2174/09298673113209990152
  51. Yankner, BA, Dawes LR, Fisher S, Villa-Komaroff L, Oster-Granite ML, Neve RL (1989) Neurotoxicity of a fragment of the amyloid precursor associated with Alzheimer's disease. Science 245: 417-420. doi: 10.1126/science.2474201
  52. Oster-Granite ML, McPhie DL, Greenan J, Neve RL (1996) Agedependent neuronal and synaptic degeneration in mice transgenic for the C terminus of the amyloid precursor protein. J Neurosci 16: 6732-6741. doi: 10.1523/JNEUROSCI.16-21-06732.1996
  53. Jiang Y, Mullaney KA, Peterhoff CM, Che S, Schmidt SD, BoyerBoiteau A, Ginsberg SD, Cataldo AM, Mathews PM, Nixon RA (2010) Alzheimer's-related endosome dysfunction in Down syndrome is Aβ-independent but requires APP and is reversed by BACE-1 inhibition. Proc Natl Acad Sci USA 107: 1630-1635. doi: 10.1073/pnas.0908953107
  54. Kim S, Sato Y, Mohan PS, Peterhoff C, Penasalfini A, Rigoglioso A, Jiang Y, Nixon RA (2016) Evidence that the rab5 effector APPL1 mediates APP-βCTF-induced dysfunction of endosomes in Down syndrome and Alzheimer's disease. Mol Psychiatry 21: 707-716 https://doi.org/10.1038/mp.2015.97
  55. Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer's diseases: progress and problems on the road to therapeutics. Science 297: 353-356. doi: 10.1126/science.1072994
  56. De Strooper B, Saftig P, Craessaerts K, Vanderstichele H, Guhde G, Annaert W, Von Figura K, Van Leuven, F (1998) Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein. Nature 391: 387-390. doi: 10.1038/34910
  57. Borchelt DR, Ratovitski T, Van Lare J, Lee MK, Gonzales V, Jenkins NA, Copeland NG, Price DL, Sisodia SS (1997) Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins. Neuron 19: 939-945. doi: 10.1016/s0896-6273(00)80974-5