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Protective Effect of Paeoniflorin on Aβ25–35-Induced SH-SY5Y Cell Injury by Preventing Mitochondrial Dysfunction

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Abstract

Alzheimer’s disease (AD) is a major neurodegenerative brain disorder affecting about 14 million people worldwide. Aβ-induced cell injury is a crucial cause of neuronal loss in AD, thus the suppression of which might be useful for the treatment of this disease. In this study, we aimed to evaluate the effect of paeoniflorin (PF), a monoterpene glycoside isolated from aqueous extract of Radix Paeoniae Alba, on Aβ25–35-induced cytotoxicity in SH-SY5Y cells. The results showed PF could attenuate or restore the viability loss, apoptotic increase, and ROS production induced by Aβ25–35 in SH-SY5Y cells. In addition, PF strikingly inhibited Aβ25–35-induced mitochondrial dysfunction, which includes decreased mitochondrial membrane potential, increased Bax/Bcl-2 ratio, cytochrome c release and activity of caspase-3 and caspase-9. Therefore, our study provided the first experimental evidence that PF could modulate ROS production and apoptotic mitochondrial pathway in model of neuron injury in vitro and which might provide new insights into its application toward Alzheimer’s disease therapy.

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References

  • Bertram L, Tanzi RE (2005) The genetic epidemiology of neurodegenerative disease. J Clin Invest 115(6):1449–1457

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Butterfield DA, Reed T, Newman SF, Sultana R (2007) Roles of amyloid β-peptide-associated oxidative stress and brain protein modifications in the pathogenesis of Alzheimer’s disease and mild cognitive impairment. Free Radical Biol Med 43(5):658–677

    Article  CAS  Google Scholar 

  • Cao BY, Yang YP, Luo WF, Mao CJ, Han R, Sun X, Cheng J, Liu CF (2010) Paeoniflorin, a potent natural compound, protects PC12 cells from MPP+ and acidic damage via autophagic pathway. J Ethnopharmacol 131(1):122–129

    Article  CAS  PubMed  Google Scholar 

  • Caroppi P, Sinibaldi F, Fiorucci L, Santucci R (2009) Apoptosis and human diseases: mitochondrion damage and lethal role of released cytochrome C as proapoptotic protein. Curr Med Chem 16(31):4058–4065

    Article  CAS  PubMed  Google Scholar 

  • Chakravarthy B, Gaudet C, Ménard M, Atkinson T, LaFerla FM, Armato U, Whitfield J (2010) Amyloid-β peptides stimulate the expression of the p75^{NTR} neurotrophin receptor in shsy5y human neuroblastoma cells and ad transgenic mice. J Alzheimers Dis 19(3):915–925

    CAS  PubMed  Google Scholar 

  • Citron M (2010) Alzheimer’s disease: strategies for disease modification. Nat Rev Drug Discovery 9(5):387–398

    Article  CAS  Google Scholar 

  • Emaus RK, Grunwald R, Lemasters JJ (1986) Rhodamine 123 as a probe of transmembrane potential in isolated rat-liver mitochondria: spectral and metabolic properties. Biochim Biophys Acta 850(3):436–448

    Article  CAS  PubMed  Google Scholar 

  • Estaquier J, Vallette F, Vayssiere JL, Mignotte B (2012) The mitochondrial pathways of apoptosis. In: Scatena R (ed) Advances in mitochondrial medicine. Springer, New York, pp 157–183

    Chapter  Google Scholar 

  • Fido RJ, Tatham AS, Shewry PR (1996) Western blotting analysis. In: jones H (ed) Plant gene transfer and expression protocols. Springer, New York, pp 423–437

    Google Scholar 

  • Gu XM, Huang HC, Jiang ZF (2012) Mitochondrial dysfunction and cellular metabolic deficiency in Alzheimer’s disease. Neurosci Bull 28(5):631–640

    Article  CAS  PubMed  Google Scholar 

  • Gurtu V, Kain SR, Zhang G (1997) Fluorometric and colorimetric detection of caspase activity associated with apoptosis. Anal Biochem 251(1):98–102

    Article  CAS  PubMed  Google Scholar 

  • Holtzman DM, John CM, Goate A (2011) Alzheimer’s disease: the challenge of the second century. Sci Transl Med. doi:10.1126/scitranslmed.3002369

    Google Scholar 

  • Honjo K, Black SE, Verhoeff NP (2012) Alzheimer’s disease, cerebrovascular disease, and the β-amyloid cascade. Can J Neurol Sci 39(6):712–728

    PubMed  Google Scholar 

  • Huang KS, Lin JG, Lee HC, Tsai FJ, Bau DT, Huang CY, Yao CH, Chen YS (2011) Paeoniae alba radix promotes peripheral nerve regeneration. Evid Based Complement Alternat Med 2011:109809

    PubMed Central  PubMed  Google Scholar 

  • Ittner LM, Götz J (2010) Amyloid-β and tau—a toxic pas de deux in Alzheimer’s disease. Nat Rev Neurosci 12(2):67–72

    Google Scholar 

  • Kruger NJ (1994) The bradford method for protein quantitation. In: Walker JM (ed) Basic protein and peptide protocols. Springer, New York, pp 9–15

    Chapter  Google Scholar 

  • Kubli DA, Gustafsson ÅB (2012) Mitochondria and mitophagy the yin and yang of cell death control. Circ Res 111(9):1208–1221

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lu H, Shi JX, Zhang DM, Shen J, Lin YX, Hang CH, Yin HX (2009) Hemolysate-induced expression of intercellular adhesion molecule-1 and monocyte chemoattractant protein-1 expression in cultured brain microvascular endothelial cells via through ros-dependent nf-κb pathways. Cell Mol Neurobiol 29(1):87–95

    Article  PubMed  Google Scholar 

  • Mao QQ, Zhong XM, Feng CR, Pan AJ, Li ZY, Huang Z (2010) Protective effects of paeoniflorin against glutamate-induced neurotoxicity in PC12 cells via antioxidant mechanisms and Ca2+ antagonism. Cell Mol Neurobiol 30(7):1059–1066

    Article  CAS  PubMed  Google Scholar 

  • Mao QQ, Xian YF, Ip SP, Tsai SH, Che CT (2011a) Protective effects of peony glycosides against corticosterone-induced cell death in PC12 cells through antioxidant action. J Ethnopharmacol 133(3):1121–1125

    Article  CAS  PubMed  Google Scholar 

  • Mao QQ, Zhong XM, Li ZY, Huang Z (2011b) Paeoniflorin protects against NMDA-induced neurotoxicity in PC12 cells via Ca2+ antagonism. Phytother Res 25(5):681–685

    CAS  PubMed  Google Scholar 

  • Mao QQ, Zhong XM, Qiu FM, Li ZY, Huang Z (2012) Protective effects of paeoniflorin against corticosterone-induced neurotoxicity in pc12 cells. Phytother Res 26(7):969–973

    Article  CAS  PubMed  Google Scholar 

  • Markesbery WR (1997) Oxidative stress hypothesis in Alzheimer’s disease. Free Radical Biol Med 23(1):134–147

    Article  CAS  Google Scholar 

  • Mazumder S, Plesca D, Almasan A (2008) Caspase-3 activation is a critical determinant of genotoxic stress-induced apoptosis. In: apoptosis and cancer. Springer, New York, pp 13–21

    Google Scholar 

  • Miranda S, Opazo C, Larrondo LF, Muñoz FJ, Ruiz F, Leighton F, Inestrosa NC (2000) The role of oxidative stress in the toxicity induced by amyloid β-peptide in Alzheimer’s disease. Prog Neurobiol 62(6):633–648

    Article  CAS  PubMed  Google Scholar 

  • Pagani L, Eckert A (2011) Amyloid-Beta interaction with mitochondria. Int J Alzheimer’s Disease 2011:925050

    Google Scholar 

  • Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP (2013) The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement 9(1):63–75

    Article  PubMed  Google Scholar 

  • Reddy PH (2009) Amyloid beta, mitochondrial structural and functional dynamics in Alzheimer’s disease. Exp Neurol 218(2):286–292

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Smith RA, Hartley RC, Cochemé HM, Murphy MP (2012) Mitochondrial pharmacology. Trends Pharmacol Sci 33(6):341–352

    Article  CAS  PubMed  Google Scholar 

  • Spuch C, Ortolano S, Navarro C (2012) New insights in the amyloid-beta interaction with mitochondria. J Aging Res 2012:324968

    Article  PubMed Central  PubMed  Google Scholar 

  • Sun R, Wang K, Wu D, Li X, Ou Y (2012) Protective effect of paeoniflorin against glutamate-induced neurotoxicity in PC12 cells via Bcl-2/Bax signal pathway. Folia Neuropathol 50(3):270–276

    Article  CAS  PubMed  Google Scholar 

  • Tam JH, Pasternak SH (2012) Amyloid and Alzheimer’s disease: inside and out. Can J Neurol Sci 39(3):286–298

    PubMed  Google Scholar 

  • Tomek M, Akiyama T, Dass CR (2012) Role of Bcl-2 in tumour cell survival and implications for pharmacotherapy. J Pharm Pharmacol 64(12):1695–1702

    Article  CAS  PubMed  Google Scholar 

  • van Meerloo J, Kaspers GJ, Cloos J (2011) Cell sensitivity assays: the MTT assay. In: Cree IA (ed) Cancer cell culture. Springer, New York, pp 237–245

    Chapter  Google Scholar 

  • Wang H, Xu Y, Yan J, Zhao X, Sun X, Zhang Y, Guo J, Zhu C (2009) Acteoside protects human neuroblastoma SH-SY5Y cells against β-amyloid-induced cell injury. Brain Res 1283:139–147

    Article  CAS  PubMed  Google Scholar 

  • Youmans KL, Tai LM, Nwabuisi-Heath E, Jungbauer L, Kanekiyo T, Gan M, Kim J, Eimer WA, Estus S, Rebeck GW (2012) APOE4-specific changes in Aβ accumulation in a new transgenic mouse model of Alzheimer disease. J Biol Chem 287(50):41774–41786

    Article  CAS  PubMed  Google Scholar 

  • Zheng GQ (2009) Therapeutic history of Parkinson’s disease in Chinese medical treatises. J Altern Complement Med 15(11):1223–1230

    Article  PubMed  Google Scholar 

  • Zhong SZ, Ge QH, Li Q, Qu R, Ma SP (2009) Peoniflorin attentuates Aβ(1-42)-mediated neurotoxicity by regulating calcium homeostasis and ameliorating oxidative stress in hippocampus of rats. J Neurol Sci 280(1):71–78

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work is supported by Grants from National Natural Science Foundation (81300787) and the Natural Science Foundation of Jiangsu Province (BK2011168, BK2012105).

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Ke Wang and other co-authors have no conflict of interest

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Correspondence to Ke Wang.

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Wang, K., Zhu, L., Zhu, X. et al. Protective Effect of Paeoniflorin on Aβ25–35-Induced SH-SY5Y Cell Injury by Preventing Mitochondrial Dysfunction. Cell Mol Neurobiol 34, 227–234 (2014). https://doi.org/10.1007/s10571-013-0006-9

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  • DOI: https://doi.org/10.1007/s10571-013-0006-9

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