Skip to main content
Log in

Protective effect of a sesamin derivative, 3-bis (3-methoxybenzyl) butane-1, 4-diol on Aβ-stressed PC12 cells

  • Research Article
  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript

Abstract

Amyloid beta-protein (Aβ) is involved in the pathogenesis of Alzheimer’s disease (AD). Aβ induces free radical production in neuronal cells, leading to oxidative stress and up-regulation of c-Jun N-terminal kinases (JNK), extracellular-signal-regulated kinases (ERK), p38 mitogen-activated protein kinase (MAPK) pathways and pro-apoptotic Bax expression. Sesamin has been shown to have protection to several models of neurodegenerative diseases by its antioxidant and anti-inflammatory properties. In the present study, we examined the neuroprotective effect of a sesamin derivative, 3-bis (3-methoxybenzyl) butane-1,4-diol (BBD) on Aβ1–42 induced cytotoxicity of PC12 cells. Aβ1–42 induced lipid peroxidation, calcium, reactive oxygen species from the PC12 cells. The effect of BBD on these harmful factors and the related signaling pathways were examined by biochemical and western blot assays. The result showed that BBD protected PC12 cells from Aβ1–42 induced cytotoxicity with the increased cell viability and acetylcholine release, and the decreased lactate dehydrogenase, malondialdehyde and calcium release. BBD significantly reduced Aβ-induced JNK, ERK, p38 MAPK pathways and Bax expression in PC12 cells. Therefore the neuroprotective effect of BBD on Aβ-induced cytotoxicity was involved with antioxidant and anti-inflammatory effects. The result would help the development of new CNS drug for protection of AD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Borovikova, L.V., S. Ivanova, M. Zhang, H. Yang, G.I. Botchkina, H.N. Abumrad, J.W. Eaton, and K.J. Tracey. 2000. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405: 458–462.

    Article  CAS  PubMed  Google Scholar 

  • Bournival, J., P. Quessy, and M.G. Martinoli. 2009. Protective effects of resveratrol and quercetin against MPP+ -induced oxidative stress act by modulating markers of apoptotic death in dopaminergic neurons. Cell Molecule Neurobiology 29: 1169–1180.

    Article  CAS  Google Scholar 

  • Drukarch, B., E. Schepens, J.C. Stoof, C.H. Langeveld, and F.L. Van Muiswinkel. 1998. Astrocyte-enhanced neuronal survival is mediated by scavenging of extracellular reactive oxygen species. Free Radical Biology and Medicine 25: 217–220.

    Article  CAS  PubMed  Google Scholar 

  • Floyd, R.A. 1999. Antioxidants, oxidative stress, and degenerative neurological disorders. Proceeding Society Experimental Biology and Medicine 222: 236–245.

    Article  CAS  Google Scholar 

  • Forman, M.S., J.Q. Trojanowski, and V.M. Lee. 2004. Neurodegenerative diseases: a decade of discoveries paves the way for therapeutic breakthroughs. Nature Medicine 10: 1055–1063.

    Article  CAS  PubMed  Google Scholar 

  • Hou, R.C., H.M. Huang, J.T. Tzen, and K.C. Jeng. 2003. Protective effects of sesamin and sesamolin on hypoxic neuronal and PC12 cells. Journal of Neuroscience Research 74: 123–133.

    Article  CAS  PubMed  Google Scholar 

  • Hou, C.W., Y.L. Chen, S.H. Chuang, and K.C. Jeng. 2014. Protective effect of a sesamin derivative, 3-bis (3-methoxybenzyl) butane-1, 4-diol on ischemic and hypoxic neuronal injury. Journal of Biomedical Science 21: 15.

    Article  PubMed  PubMed Central  Google Scholar 

  • Hu, J.F., S.F. Chu, N. Ning, Y.H. Yuan, W. Xue, N.H. Chen, and J.T. Zhang. 2010. Protective effect of (−) Clausenamide against Aβ-induced neurotoxicity in differentiated PC12 cells. Neuroscience Letters 483: 78–82.

    Article  CAS  PubMed  Google Scholar 

  • Huang, H.M., Ou Hsio-Chung, and S.J. Hsieh. 2000. Antioxidants prevent amyloid peptide-induced apoptosis and alteration of calcium homeostasis in cultured cortical neurons. Life Science 66: 1879–1892.

    Article  CAS  Google Scholar 

  • Huang, T.C., K.T. Lu, Y.Y. Wo, Y.J. Wu, and Y.L. Yang. 2011. Resveratrol protects rats from Aβ-induced neurotoxicity by the reduction of iNOS expression and lipid peroxidation. PLoS One 6: e29102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hwang, S.L., and G.C. Yen. 2008. Neuroprotective effects of the citrus flavanones against H2O2-induced cytotoxicity in PC12 cells. Journal of Agriculture and Food Chemistry 56: 859–864.

    Article  CAS  Google Scholar 

  • Jang, J.H., and Y.J. Surh. 2005. Beta-amyloid-induced apoptosis is associated with cyclooxygenase-2 up-regulation via the mitogen-activated protein kinase-NF-kappaB signaling pathway. Free Radical Biology and Medicine 38: 1604–1613.

    Article  CAS  PubMed  Google Scholar 

  • Jeong, J.H., H.R. Jeong, Y.N. Jo, H.J. Kim, J.H. Shin, and H.J. Heo. 2013. Ameliorating effects of aged garlic extracts against Aβ-induced neurotoxicity and cognitive impairment. BMC Complementary and Alternative Medicine 13: 268.

    Article  PubMed  PubMed Central  Google Scholar 

  • Khodadadi, S., G.H. Riazi, S. Ahmadian, E. Hoveizi, O. Karima, and H. Aryapour. 2012. Effect of N-homocysteinylation on physicochemical and cytotoxic properties of amyloid beta-peptide. FEBS Letters 586: 127–131.

    Article  CAS  PubMed  Google Scholar 

  • Kudo, W., H.P. Lee, M.A. Smith, X. Zhu, S. Matsuyama, and H.G. Lee. 2012. Inhibition of Bax protects neuronal cells from oligomeric Aβ neurotoxicity. Cell Death and Disease 3: e309.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li, G., R. Ma, C. Huang, Q. Tang, Q. Fu, H. Liu, B. Hu, and J. Xiang. 2008. Protective effect of erythropoietin on beta-amyloid-induced PC12 cell death through antioxidant mechanisms. Neuroscience Letters 442: 143–147.

    Article  CAS  PubMed  Google Scholar 

  • Lievre, V., P. Becuwe, and A. Bianchi. 2001. Intracellular generation of free radicals and modifications of detoxifying enzymes in cultured neurons from the developing rat forebrain in response to transient hypoxia. Neuroscience 105: 287–297.

    Article  CAS  PubMed  Google Scholar 

  • Muthaiyah, B., M.M. Essa, V. Chauhan, and A. Chauhan. 2011. Protective effects of walnut extract against amyloid beta peptide-induced cell death and oxidative stress in PC12 cells. Neurochemical Research 36: 2096–2103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nordberg, A. 2004. Functional studies of cholinergic activity in normal and Alzheimer disease states by imaging technique. Progress in Brain Research 145: 301–310.

    Article  CAS  PubMed  Google Scholar 

  • Nozaki, K., M. Nishimura, and N. Hashimoto. 2001. Mitogen-activated protein kinases and cerebral ischemia. Molecule Neurobiology 23: 1–19.

    Article  CAS  Google Scholar 

  • Pagani, L., and A. Eckert. 2011. Amyloid-Beta interaction with mitochondria. International Journal Alzheimers Disease 2011: 925050.

    Google Scholar 

  • Ramin, M., P. Azizi, F. Motamedi, A. Haghparast, and F. Khodagholi. 2011. Inhibition of JNK phosphorylation reverses memory deficit induced by β-amyloid (1-42) associated with decrease of apoptotic factors. Behavioural Brain Research 217: 424–431.

    Article  CAS  PubMed  Google Scholar 

  • Regan, R.F., Y. Wang, X. Ma, A. Chong, and Y. Guo. 2001. Activation of extracellular signal-regulated kinases potentiates hemin toxicity in astrocyte cultures. Journal of Neurochemistry 79: 545–555.

    Article  CAS  PubMed  Google Scholar 

  • Selkoe, D.J. 2008. Soluble oligomers of the amyloid β-protein impair synaptic plasticity and behavior. Behavioural Brain Research 192: 106–113.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shanks, M., M. Kivipelto, R. Bullock, and R. Lane. 2009. Cholinesterase inhibition: Is there evidence for disease-modifying effects? Current Medical Research and Opinion 25: 2439–2446.

    Article  CAS  PubMed  Google Scholar 

  • Suen, K.C., K.F. Lin, W. Elyaman, K.F. So, R.C. Chang, and J. Hugon. 2003. Reduction of calcium release from the endoplasmic reticulum could only provide partial neuroprotection against beta-amyloid peptide toxicity. Journal of Neurochemistry 87: 1413–1426.

    Article  CAS  PubMed  Google Scholar 

  • Taepavarapruk, P., and C. Song. 2010. Reductions of acetylcholine release and nerve growth factor expression are correlated with memory impairment induced by interleukin-1beta administrations: Effects of omega-3 fatty acid EPA treatment J. Journal of Neurochemistry 112: 1054–1064.

    Article  CAS  PubMed  Google Scholar 

  • Tanzi, R.E., and L. Bertram. 2005. Twenty years of the Alzheimer’s disease amyloid hypothesis: a genetic perspective. Cell 120: 545–555.

    Article  CAS  PubMed  Google Scholar 

  • Wang, R., J. Zhou, and X.C. Tang. 2002. Tacrine attenuates hydrogen peroxide-induced apoptosis by regulating expression of apoptosis-related genes in rat PC12 cells. Molecular Brain Research 107: 1–8.

    Article  CAS  PubMed  Google Scholar 

  • Xiao, X.Q., R. Wang, and X.C. Tang. 2000. Huperzine A and tacrine attenuate β-amyloid peptide-induced oxidative injury. Journal of Neuroscience Research 61: 564–569.

    Article  CAS  PubMed  Google Scholar 

  • Yan, M.H., X. Wang, and X. Zhu. 2013. Mitochondrial defects and oxidative stress in Alzheimer disease and Parkinson disease. Free Radical Biology and Medicine 62: 90–101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang, H.Y., X.C. Tang, and B. Huperzine. 2000. A novel acetylcholinesterase inhibitor, attenuates hydrogen peroxide induced injury in PC12 cells. Neuroscience Letters 292: 41–44.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported in part by a Grant TTMHH103R0004 from Tung’s Taichung MetroHarbor Hospital and a research grant from Yuanpei University.

Conflict of interest

The authors have no financial conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kee-Ching Jeng.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hou, CW., Chang, SY. & Jeng, KC. Protective effect of a sesamin derivative, 3-bis (3-methoxybenzyl) butane-1, 4-diol on Aβ-stressed PC12 cells. Arch. Pharm. Res. 38, 543–548 (2015). https://doi.org/10.1007/s12272-014-0426-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12272-014-0426-1

Keywords

Navigation