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Eriodictyol Attenuates β-Amyloid 25–35 Peptide-Induced Oxidative Cell Death in Primary Cultured Neurons by Activation of Nrf2

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Abstract

Oxidative stress plays an important role in the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease (AD). Eriodictyol, a flavonoid isolated from the Chinese herb Dracocephalum rupestre, has long been established as an antioxidant. The present study was designed to investigate the effect of eriodictyol on β-amyloid 25–35 peptide (Aβ25–35)-induced oxidative cell death in primary neurons and to explore the role of the nuclear factor erythroid-2-related factor 2/antioxidant response element (Nrf2/ARE) pathway in this process. For this purpose, primary cultures of cortical neurons were exposed to 15 μM Aβ25–35 in the absence or presence of eriodictyol (20, 40 and 80 μM). The results revealed that Aβ25–35-induced cytotoxicity and apoptotic characteristics such as activation of JNK/p38 apoptotic signaling pathway were effectively attenuated by eriodictyol pretreatment. Eriodictyol treatment also resulted in an increase in Nrf2 protein levels and subsequent activation of ARE pathway genes in primary cultured neurons. The protective effects of eriodictyol were attenuated by RNA interference-mediated knockdown of Nrf2 expression. Taken together, these results clearly demonstrate that eriodictyol protects neurons against Aβ25–35-induced cell death partially through Nrf2/ARE signaling pathway, which further supports that eriodictyol might be a promising novel therapeutic agent for AD.

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References

  1. Selkoe DJ (2012) Preventing Alzheimer’s disease. Science 337:1488–1492

    Article  CAS  PubMed  Google Scholar 

  2. Querfurth HW, LaFerla FM (2010) Alzheimer’s disease. N Engl J Med 362:329–344

    Article  CAS  PubMed  Google Scholar 

  3. Deshpande A, Mina E, Glabe C, Busciglio J (2006) Different conformations of amyloid beta induce neurotoxicity by distinct mechanisms in human cortical neurons. J Neurosci 26:6011–6018

    Article  CAS  PubMed  Google Scholar 

  4. Nunomura A, Castellani RJ, Zhu X, Moreira PI, Perry G, Smith MA (2006) Involvement of oxidative stress in Alzheimer disease. J Neuropathol Exp Neurol 65:631–641

    Article  CAS  PubMed  Google Scholar 

  5. Calkins MJ, Johnson DA, Townsend JA, Vargas MR, Dowell JA, Williamson TP, Kraft AD, Lee JM, Li J, Johnson JA (2009) The Nrf2/ARE pathway as a potential therapeutic target in neurodegenerative disease. Antioxid Redox Signal 11:497–508

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Yang Y, Jiang S, Yan J, Li Y, Xin Z, Lin Y, Qu Y (2014) An overview of the molecular mechanisms and novel roles of Nrf2 in neurodegenerative disorders. Cytokine Growth Factor Rev. 26:47–57

    Article  PubMed  Google Scholar 

  7. Ramsey C, Glass CA, Montgomery MB, Lindl KA, Ritson GP, Chia LA, Hamilton RL, Chu CT, Jordan-Sciutto KL (2007) Expression of Nrf2 in neurodegenerative diseases. J Neuropathol Exp Neurol 66:75–85

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Kanninen K, Malm TM, Jyrkkänen HK, Goldsteins G, Keksa-Goldsteine V, Tanila H, Yamamoto M, Ylä-Herttuala S, Levonen AL, Koistinaho J (2008) Nuclear factor erythroid 2-related factor 2 protects against beta amyloid. Mol Cell Neurosci 39:302–313

    Article  CAS  PubMed  Google Scholar 

  9. Baptista FI, Henriques AG, Silva AM, Wiltfang J, da Cruz e Silva OA (2014) Flavonoids as therapeutic compounds targeting key proteins involved in Alzheimer’s disease. ACS Chem Neurosci 5:83–92

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Johnson J, Maher P, Hanneken A (2009) The flavonoid, eriodictyol, induces long-term protection in ARPE-19 cells through its effects on Nrf2 activation and phase 2 gene expression. Invest Ophthalmol Vis Sci 50:2398–2406

    Article  PubMed Central  PubMed  Google Scholar 

  11. Lou H, Jing X, Ren D, Wei X, Zhang X (2012) Eriodictyol protects against H2O2-induced neuron-like PC12 cell death through activation of Nrf2/ARE signaling pathway. Neurochem Int 61:251–257

    Article  CAS  PubMed  Google Scholar 

  12. Gan Y, Ji X, Hu X, Luo Y, Zhang L, Li P, Liu X, Yan F, Vosler P, Gao Y, Stetler RA, Chen J (2012) Transgenic overexpression of peroxiredoxin-2 attenuates ischemic neuronal injury via suppression of a redox-sensitive pro-death signaling pathway. Antioxid Redox Signal 17:719–732

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Frozza RL, Horn AP, Hoppe JB, Simão F, Gerhardt D, Comiran RA, Salbego CG (2009) A comparative study of beta-amyloid peptides Aβ1–42 and Aβ25–35 toxicity in organotypic hippocampal slice cultures. Neurochem Res 34:295–303

    Article  CAS  PubMed  Google Scholar 

  14. Lou H, Fan P, Perez RG, Lou H (2011) Neuroprotective effects of linarin through activation of the PI3 K/Akt pathway in amyloid-β-induced neuronal cell death. Bioorg Med Chem 19:4021–4027

    Article  CAS  PubMed  Google Scholar 

  15. Jing X, Ren D, Wei X, Shi H, Zhang X, Perez RG, Lou H, Lou H (2013) Eriodictyol-7-O-glucoside activates Nrf2 and protects against cerebral ischemic injury. Toxicol Appl Pharmacol 273:672–679

    Article  CAS  PubMed  Google Scholar 

  16. Cheng J, Uchida M, Zhang W, Grafe MR, Herson PS, Hurn PD (2011) Role of salt-induced kinase 1 in androgen neuroprotection against cerebral ischemia. J Cereb Blood Flow Metab 31:339–350

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Solanki I, Parihar P, Mansuri ML, Parihar MS (2015) Flavonoid-based therapies in the early management of neurodegenerative diseases. Adv Nutr 6:64–72

    Article  CAS  PubMed  Google Scholar 

  18. Leonardo CC, Doré S (2011) Dietary flavonoids are neuroprotective through Nrf2-coordinated induction of endogenous cytoprotective proteins. Nutr Neurosci 14:226–236

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Eftekharzadeh B, Maghsoudi N, Khodagholi F (2010) Stabilization of transcription factor Nrf2 by tBHQ prevents oxidative stress-induced amyloid beta formation in NT2 N neurons. Biochimie 92:245–253

    Article  CAS  PubMed  Google Scholar 

  20. Kim HV, Kim HY, Ehrlich HY, Choi SY, Kim DJ, Kim Y (2013) Amelioration of Alzheimer’s disease by neuroprotective effect of sulforaphane in animal model. Amyloid 20:7–12

    Article  CAS  PubMed  Google Scholar 

  21. Lee C, Park GH, Lee SR, Jang JH (2013) Attenuation of β-amyloid-induced oxidative cell death by sulforaphane via activation of NF-E2-related factor 2. Oxid Med Cell Longev 2013:313510

    PubMed Central  PubMed  Google Scholar 

  22. Dumont M, Wille E, Calingasan NY, Tampellini D, Williams C, Gouras GK, Liby K, Sporn M, Nathan C, Flint Beal M, Lin MT (2009) Triterpenoid CDDO-methylamide improves memory and decreases amyloid plaques in a transgenic mouse model of Alzheimer’s disease. J Neurochem 109:502–512

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Chao XJ, Chen ZW, Liu AM, He XX, Wang SG, Wang YT, Liu PQ, Ramassamy C, Mak SH, Cui W, Kong AN, Yu ZL, Han YF, Pi RB (2014) Effect of tacrine-3-caffeic acid, a novel multifunctional anti-Alzheimer’s dimer, against oxidative-stress-induced cell death in HT22 hippocampal neurons: involvement of Nrf2/HO-1 pathway. CNS Neurosci Ther 20:840–850

    Article  CAS  PubMed  Google Scholar 

  24. Joshi G, Gan KA, Johnson DA, Johnson JA (2015) Increased Alzheimer’s disease-like pathology in the APP/PS1ΔE9 mouse model lacking Nrf2 through modulation of autophagy. Neurobiol Aging 36:664–679

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This study was supported by Grants from the National Natural Science Foundation of China (Nos. 81274124 and 81173528) and Shandong Province Science and Technology Program (No. 2014GSF118038).

Conflict of interest

The authors declare that there are no conflicts of interest.

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Author notes

  1. Xu Jing

    Present address: Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University, Jinan, 250012, China

Authors and Affiliations

  1. Department of Pharmacology, School of Medicine, Shandong University, No. 44 Wenhua Xi Road, Jinan, 250012, Shandong Province, China

    Xu Jing, Huanying Shi, Xinbing Wei, Manru Ren, Minxing Han & Haiyan Lou

  2. Department of Neurosurgery, Yucheng Renmin Hospital, Yucheng, 251200, China

    Xiuying Zhu

  3. Department of Natural Product Chemistry, Key Lab of Chemical Biology of MOE (Ministry of Education), Shandong University, Jinan, 250012, China

    Dongmei Ren

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  1. Xu Jing
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Corresponding author

Correspondence to Haiyan Lou.

Additional information

Xu Jing and Huanying Shi have contributed equally to this work.

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Jing, X., Shi, H., Zhu, X. et al. Eriodictyol Attenuates β-Amyloid 25–35 Peptide-Induced Oxidative Cell Death in Primary Cultured Neurons by Activation of Nrf2. Neurochem Res 40, 1463–1471 (2015). https://doi.org/10.1007/s11064-015-1616-z

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  • DOI: https://doi.org/10.1007/s11064-015-1616-z

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