Skip to main content

Advertisement

SpringerLink
Log in

Studies on the Neuroprotection of Osthole on Glutamate-Induced Apoptotic Cells and an Alzheimer’s Disease Mouse Model via Modulation Oxidative Stress

  • Published:
Applied Biochemistry and Biotechnology Aims and scope Submit manuscript

Abstract

In the present study, the neuroprotection of osthole (OST) was confirmed. In l-glutamic acid (l-Glu)-damaged HT22 cells, a 3-h pre-incubation with OST-enhanced cell viability suppressed the apoptosis rate; inhibited the activities of caspase-3, caspase-8, and caspase-9; reduced the over-accumulation of intracellular reactive oxygen species; restored the dissipated mitochondrial membrane potential; and regulated the expression levels of B cell lymphoma-2 (Bcl-2), Bax, cleaved poly (ADP-ribose) polymerase (PARP), NF-E2p45-related factor 2 (Nrf2), and its downstream proteins. In amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice, an 8-week OST administration improved the pathological behaviors related to memory and cognition, and reduced the expression levels of 4-hydroxynonenal, the deposition of β-amyloid peptides and neuronal fiber tangles formed by the high phosphor-Tau in the brain. OST enhanced the expression levels of Nrf2 and its downstream proteins including superoxide dismutase-1 (SOD-1) and heme oxygenase-1 (HO-1). The present data confirmed the protection of OST against AD-like symptoms via modulating oxidative stress, especially Nrf2 signaling.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Cheignon, C., Tomas, M., Bonnefont-Rousselot, D., Faller, P., Hureau, C., & Collin, F. (2018). Oxidative stress and the amyloid beta peptide in Alzheimer’s disease. Redox Biology, 14, 450–464.

    Article  CAS  Google Scholar 

  2. de Oliveira, R. B., Gravina, F. S., Lim, R., Brichta, A. M., Callister, R. J., & van Helden, D. F. (2012). Heterogeneous responses to antioxidants in noradrenergic neurons of the locus coeruleus indicate differing susceptibility to free radical content. Oxidative Medicine and Cellular Longevity, 2012, 820285.

    Article  Google Scholar 

  3. Rosello, A., Warnes, G., & Meier, U. C. (2012). Cell death pathways and autophagy in the central nervous system and its involvement in neurodegeneration, immunity and central nervous system infection: to die or not to die--that is the question. Clinical and Experimental Immunology, 168(1), 52–57.

    Article  CAS  Google Scholar 

  4. Kim, D. H., Kim, D. W., Jung, B. H., Lee, J. H., Lee, H., Hwang, G. S., Kang, K. S., & Lee, J. W. (2019). Ginsenoside Rb2 suppresses the glutamate-mediated oxidative stress and neuronal cell death in HT22 cells. Journal of Ginseng Research, 43(2), 326–334.

    Article  Google Scholar 

  5. Joshi, G., Gan, K. A., Johnson, D. A., & Johnson, J. A. (2015). Increased Alzheimer’s disease-like pathology in the APP/ PS1DeltaE9 mouse model lacking Nrf2 through modulation of autophagy. Neurobiology of Aging, 36(2), 664–679.

    Article  CAS  Google Scholar 

  6. Deshpande, P., Gogia, N., & Singh, A. (2019). Exploring the efficacy of natural products in alleviating Alzheimer’s disease. Neural Regeneration Research, 14(8), 1321–1329.

    Article  Google Scholar 

  7. Bi, D. B., Yang, M. S., Zhao, X., & Huang, S. M. (2015). Effect of Cnidium lactone on serum mutant P53 and BCL-2/BAX expression in human prostate cancer cells PC-3 tumor-bearing BALB/C nude mouse model. Medical Science Monitor, 21, 2421–2427.

    Article  CAS  Google Scholar 

  8. Fan, H., Gao, Z., Ji, K., Li, X., Wu, J., Liu, Y., Wang, X., Liang, H., Liu, Y., Li, X., Liu, P., Chen, D., & Zhao, F. (2019). The in vitro and in vivo anti-inflammatory effect of osthole, the major natural coumarin from Cnidium monnieri (L.) Cuss, via the blocking of the activation of the NF-kappaB and MAPK/p38 pathways. Phytomedicine: International Journal of Phytotherapy and Phytopharmacology, 58, 152864.

    Article  CAS  Google Scholar 

  9. Li, Z., Chen, X., Lu, W., Zhang, S., Guan, X., Li, Z., & Wang, D. (2017). Anti-oxidative stress activity is essential for Amanita caesarea mediated neuroprotection on glutamate-induced apoptotic HT22 cells and an Alzheimer’s disease mouse model. International Journal of Molecular Sciences, 18(8).

  10. An, S., Lu, W., Zhang, Y., Yuan, Q., & Wang, D. (2017). Pharmacological basis for use of Armillaria mellea polysaccharides in Alzheimer’s disease: antiapoptosis and antioxidation. Oxidative Medicine and Cellular Longevity, 2017, 4184562.

    PubMed  PubMed Central  Google Scholar 

  11. Liot, G., Bossy, B., Lubitz, S., Kushnareva, Y., Sejbuk, N., & Bossy-Wetzel, E. (2009). Complex II inhibition by 3-NP causes mitochondrial fragmentation and neuronal cell death via an NMDA- and ROS-dependent pathway. Cell Death and Differentiation, 16(6), 899–909.

    Article  CAS  Google Scholar 

  12. Bivik, C. A., Larsson, P. K., Kagedal, K. M., Rosdahl, I. K., & Ollinger, K. M. (2006). UVA/B-induced apoptosis in human melanocytes involves translocation of cathepsins and Bcl-2 family members. The Journal of Investigative Dermatology, 126(5), 1119–1127.

    Article  CAS  Google Scholar 

  13. Piskunova TS, Yurova MN, Ovsyannikov AI, Semenchenko AV, Zabezhinski MA, Popovich IG, Wang ZQ, Anisimov VN (2008) Deficiency in poly(ADP-ribose) polymerase-1 (PARP-1) accelerates aging and spontaneous carcinogenesis in mice. Current Gerontology and Geriatrics Research 754190

  14. McKee, A. E., & Thiele, C. J. (2006). Targeting caspase 8 to reduce the formation of metastases in neuroblastoma. Expert Opinion on Therapeutic Targets, 10(5), 703–708.

    Article  CAS  Google Scholar 

  15. Li, P., Zhou, L., Zhao, T., Liu, X., Zhang, P., Liu, Y., Zheng, X., & Li, Q. (2017). Caspase-9: structure, mechanisms and clinical application. Oncotarget, 8(14), 23996–24008.

    PubMed  PubMed Central  Google Scholar 

  16. Tang, X.-Q., Feng, J.-Q., Chen, J., Chen, P.-X., Zhi, J.-L., Cui, Y., Guo, R.-X., & Yu, H.-M. (2005). Protection of oxidative preconditioning against apoptosis induced by H2O2 in PC12 cells: mechanisms via MMP, ROS, and Bcl-2. Brain Research, 1057(1–2), 57–64.

    Article  CAS  Google Scholar 

  17. Bilkei-Gorzo, A. (2014). Genetic mouse models of brain ageing and Alzheimer’s disease. Pharmacology & Therapeutics, 142(2), 244–257.

    Article  CAS  Google Scholar 

  18. Varadarajan, S., Yatin, S., Aksenova, M., & Butterfield, D. A. (2000). Review: Alzheimer’s amyloid beta-peptide-associated free radical oxidative stress and neurotoxicity. Journal of Structural Biology, 130(2–3), 184–208.

    Article  CAS  Google Scholar 

  19. Calderon-Garciduenas, A. L., & Duyckaerts, C. (2017). Alzheimer disease. Handbook of Clinical Neurology, 145, 325–337.

    Article  Google Scholar 

  20. Kim, D. I., Lee, K. H., Gabr, A. A., Choi, G. E., Kim, J. S., Ko, S. H., & Han, H. J. (2016). A beta-induced Drp1 phosphorylation through Akt activation promotes excessive mitochondrial fission leading to neuronal apoptosis. Biochimica et Biophysica Acta, 1863(11), 2820–2834.

    Article  CAS  Google Scholar 

  21. Santana, I., Baldeiras, I., Santiago, B., Duro, D., Freitas, S., Pereira, M. T., Almeida, M. R., & Oliveira, C. R. (2018). Underlying biological processes in mild cognitive impairment: amyloidosis versus neurodegeneration. Journal of Alzheimer's Disease, 64(s1), S647–SS57.

    Article  CAS  Google Scholar 

  22. Kaur, S. J., McKeown, S. R., & Rashid, S. (2016). Mutant SOD1 mediated pathogenesis of amyotrophic lateral sclerosis. Gene, 577(2), 109–118.

    Article  CAS  Google Scholar 

  23. Hettiarachchi, N., Dallas, M., Al-Owais, M., Griffiths, H., Hooper, N., Scragg, J., Boyle, J., & Peers, C. (2014). Heme oxygenase-1 protects against Alzheimer’s amyloid-beta(1-42)-induced toxicity via carbon monoxide production. Cell Death & Disease, 5(12), e1569.

    Article  CAS  Google Scholar 

  24. Butterfield, D. A., Castegna, A., Lauderback, C. M., & Drake, J. (2002). Evidence that amyloid beta-peptide-induced lipid peroxidation and its sequelae in Alzheimer’s disease brain contribute to neuronal death. Neurobiology of Aging, 23(5), 655–664.

    Article  Google Scholar 

  25. Fossati, S., Giannoni, P., Solesio, M. E., Cocklin, S. L., Cabrera, E., Ghiso, J., & Rostagno, A. (2016). The carbonic anhydrase inhibitor methazolamide prevents amyloid beta-induced mitochondrial dysfunction and caspase activation protecting neuronal and glial cells in vitro and in the mouse brain. Neurobiology of Disease, 86, 29–40.

    Article  CAS  Google Scholar 

  26. Spilovska, K., Korabecny, J., Nepovimova, E., Dolezal, R., Mezeiova, E., Soukup, O., & Kuca, K. (2017). Multitarget tacrine hybrids with neuroprotective properties to confront Alzheimer’s disease. Current Topics in Medicinal Chemistry, 17(9), 1006–1026.

    Article  CAS  Google Scholar 

  27. Zhao, J. M., Li, L., Chen, L., Shi, Y., Li, Y. W., Shang, H. X., Wu, L. Y., Weng, Z. J., Bao, C. H., & Wu, H. G. (2017). Comparison of the analgesic effects between electro-acupuncture and moxibustion with visceral hypersensitivity rats in irritable bowel syndrome. World Journal of Gastroenterology, 23(16), 2928–2939.

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported by the Medical Health Project in Jilin Province of P. R. China (Grant No.20191102027YY), “Thirteenth Five-Year” Science and Technology Planning Project of Jilin Province in P. R. China (Grant No. JJKH20190060KJ), and the Science Foundation of Jilin Province in P. R. China (Grant No. 20180101098JC).

Author information

Authors and Affiliations

  1. Department of Neurology, the Second Hospital of Jilin University, Jilin University, Changchun, 130041, China

    Qiubo Chu & Yizhi Zhang

  2. School of Life Sciences, Jilin University, Changchun, 130012, China

    Qiubo Chu, Yanfeng Zhu, Tianjiao Cao, Yi Zhang, Yan Liu & Jiahui Lu

  3. School of Public Health, Jilin University, Changchun, 130012, Jilin, China

    Zecheng Chang

Authors
  1. Qiubo Chu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yanfeng Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tianjiao Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yi Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zecheng Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jiahui Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yizhi Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yizhi Zhang.

Ethics declarations

Conflict of Interest

The authors declare that there is no conflict of interest.

Ethical Approval

The experimental animal protocol was approved by the Animal Ethics Committee of the Second Hospital of Jilin University (20171201).

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chu, Q., Zhu, Y., Cao, T. et al. Studies on the Neuroprotection of Osthole on Glutamate-Induced Apoptotic Cells and an Alzheimer’s Disease Mouse Model via Modulation Oxidative Stress. Appl Biochem Biotechnol 190, 634–644 (2020). https://doi.org/10.1007/s12010-019-03101-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12010-019-03101-2

Keywords

Search

Navigation