Skip to main content

Advertisement

SpringerLink
Log in

Limonoids from Dictamnus dasycarpus Protect Against Glutamate-induced Toxicity in Primary Cultured Rat Cortical Cells

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

In our previous report, four limonoids, obacunone, limonin, fraxinellone, and calodendrolide, isolated from Dictamnus dasycarpus showed significant neuroprotective activity against glutamate toxicity in primary cultured rat cortical cells. This study investigated neuroprotective mechanism of these compounds using the same in vitro culture system. These four compounds showed significant neuroprotective activity at the concentration of 0.1 μM. They effectively inhibited calcium influx and overproduction of cellular nitric oxide and reactive oxygen species accompanied by glutamate-induced neurotoxicity. In addition, these compounds significantly preserved mitochondrial membrane potential and activities of antioxidative enzymes. Our results showed that obacunone, limonin, fraxinellone, and calodendrolide significantly protect primary culture cortical cells against glutamate-induced toxicity by preserving the antioxidant defense system. These compounds might offer potential drug development candidate for various neurodegenerative diseases involved with glutamate.

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

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  • Abdelgaleil SA, Iwagawa T, Doe M, Nakatani M (2004) Antifungal limonoids from the fruits of Khaya senegalensis. Fitoterapia 75:566–572

    Article  CAS  PubMed  Google Scholar 

  • Alibright TD, Jessel TM, Kandel ER, Poster MI (2000) Neural science: a century of progress and the mysteries that remain. Cell 18:209–216

    Google Scholar 

  • Atlante A, Calissano P, Bobba A, Giannattaso S, Marra E, Passarella S (2001) Glutamate neurotoxicity, oxidative stress and mitochondria. FEBS Lett 497:1–5

    Article  CAS  PubMed  Google Scholar 

  • Battinelli L, Mengoni F, Lichtner M, Mazzanti G, Saija A, Mastroianni CM, Vullo V (2003) Effect of limonin and nomilin on HIV-1 replication on infected human mononuclear cells. Planta Med 69:910–913

    Article  CAS  PubMed  Google Scholar 

  • Bondy SC, Lee D (1993) Oxidative stress induced by glutamate receptor agonists. Brain Res 610:229–233

    Article  CAS  PubMed  Google Scholar 

  • Calberg I, Mannervik B (1975) Purification and characterization of the flavoenzyme glutathione reductase from rat liver. J Biol Chem 250:5475–5480

    Google Scholar 

  • Choi DW (1985) Glutamate neurotoxicity in cortical cell cultures is calcium dependent. Neurosci Lett 58:293–297

    Article  CAS  PubMed  Google Scholar 

  • Choi DW (1987) Ionic dependence of glutamate neurotoxicity. J Neurosci 7:369–379

    CAS  PubMed  Google Scholar 

  • Choi DW (1998) Glutamate neurotoxicity and disease of the nervous system. Neuron 1:623–634

    Article  Google Scholar 

  • Dawson VL, Brahmbhatt HP, Mong JA, Dawson TM (1994) Expression of inducible nitric oxide synthase causes delayed neurotoxicity in primary mixed neuronal-glial cortical cultures. Neuropharmacology 33:1425–1430

    Article  CAS  PubMed  Google Scholar 

  • Duchen M (2000) Mitochondria and calcium: from cell signaling to cell death. J Physiol 529:57–68

    Article  CAS  PubMed  Google Scholar 

  • Flohe L, Gunzler WA (1984) Assays of glutathione peroxidase. Method Enzymol 105:114–121

    Article  CAS  Google Scholar 

  • Germano MP, D’Angelo V, Sanogo R, Catania S, Alma R, De Pasquale R, Bisignano G (2005) Hepatoprotective and antibacterial effects of extracts from Trichilia emetica Vahl. (Meliaceae). J Ethnopharmacol 96:227–232

    Article  CAS  PubMed  Google Scholar 

  • Gibson GG, Skelf P (1988) Techniques and experiments illustrating drug metabolism. In: Gibson GG, Skelf P (eds) Introduction to drug metabolism. Chapman and Hall press, New York, pp 239–271

    Google Scholar 

  • Goodman Y, Mattson MP (1994) Selected forms of β-amyloid precursor protein protect hippocampal neurons against amyloid β-peptide induced oxidative injury. Exp Neurol 128:1–12

    Article  CAS  PubMed  Google Scholar 

  • Grynkiewicz G, Poenie M, Tsien RY (1985) A new generation of calcium indicators with greatly improved fluorescence properties. J Biol Chem 260:3440–3450

    CAS  PubMed  Google Scholar 

  • Kim SR, Sung SH, Kang SY, Koo KA, Kim SH, Ma CJ, Lee HS, Park MJ, Kim YC (2004) Aristolactam BII of Saururus chinensis attenuates glutamate-induced neurotoxicity in rat cortical cultures probably by inhibiting nitric oxide production. Planta Med 70:391–396

    Article  CAS  PubMed  Google Scholar 

  • Lafon-Cazal M, Pietri S, Culcasi M, Bockaert J (1993) NMDA-dependent superoxide production and neurotoxicity. Nature 364:535–537

    Article  CAS  PubMed  Google Scholar 

  • Lipton SA, Rosenberg PA (1994) Excitatory amino acids as a final common pathway for neurologic disorders. N Eng J Med 330:613–622

    Article  CAS  Google Scholar 

  • Love S (1999) Oxidative stress in brain ischemia. Brain Pathol 9:119–131

    Article  CAS  PubMed  Google Scholar 

  • Lowry O, Rosebrough H, Farr A, Randall R (1951) Protein measurement with folin phenol reagent. J Biol Chem 193:265–275

    CAS  PubMed  Google Scholar 

  • McCord JM, Fridovich I (1969) Superoxide dismutase. J Biol Chem 244:6049–6055

    CAS  PubMed  Google Scholar 

  • Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63

    Article  CAS  PubMed  Google Scholar 

  • Ogita K, Okuda H, Kitano M, Fujinami Y, Ozaki K, Yneda Y (2002) Localization of activator protein-1 complex with DNA binding activity in mitochondria of murine barin after in vivo treatment with kainate. J Neurosci 22:2561–2570

    CAS  PubMed  Google Scholar 

  • Pellerin L, Wolfe LS (1991) Release of arachidonic acid by NMDA-receptor activation in the rat hippocampus. Neurochem Res 16:983–989

    Article  CAS  PubMed  Google Scholar 

  • Pereira CF, Oliveira CR (2000) Oxidative glutamate toxicity involves mitochondrial dysfunction and perturbation of intracellular Ca2+ homeostasis. Neurosci Res 37:227–236

    Article  CAS  PubMed  Google Scholar 

  • Perry SW, Norman JP, Litzburg A, Glebard HA (2004) Antioxidants are required during the early critical period, but not later for neuronal survival. J Neurosci Res 78:485–492

    Article  CAS  PubMed  Google Scholar 

  • Raps SP, Lai JC, Hertz C, Copper AJ (1989) Glutathione is present in high concentrations in cultured astrocytes but not in cultured neurons. Brain Res 493:398–401

    Article  Google Scholar 

  • Rita S, Michael T (2000) Molecular mechanisms of calcium-dependent excitotoxicity. J Mol Med 78:3–13

    Article  Google Scholar 

  • Roy A, Saraf S (2006) Limonoids: overview of significant bioactive triterpenes distributed in plants kingdom. Biol Pharm Bull 29:191–201

    Article  CAS  PubMed  Google Scholar 

  • Tian Q, Miller EG, Ahmad H, Tang L, Patil BS (2001) Differential inhibition of human cancer cell proliferation by citrus limonoids. Nutr Cancer 40:180–184

    Article  CAS  PubMed  Google Scholar 

  • Tietz F (1969) Enzymatic method for quantitative determination of nanogram amounts of total and oxidized glutathione. Anal Biochem 27:502–522

    Article  Google Scholar 

  • Warner DS, Sheng H, Batinc-Haberle I (2004) Oxidant, antioxidants and the ischemic brain. J Exp Biol 207:3221–3231

    Article  CAS  PubMed  Google Scholar 

  • Weikert S, Freyer D, Weh M, Lsaev N, Busch C, Schultze J, Megow D, Dirnal U (1997) Rapid Ca2+ dependent NO-production from central nervous system cells in culture measured by NO-nitrite/ozone chemoluminescence. Brain Res 748:1–11

    Article  CAS  PubMed  Google Scholar 

  • Yoon JS, Sung SH, Kim YC (2008) Neuroprotective limonoids of root bark of Dictamnus dasycarpus. J Nat Prod 71:208–211

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2009-0075964).

Author information

Authors and Affiliations

  1. College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, San 56-1, Sillim-Dong, Gwanak-Gu, Seoul, 151-742, South Korea

    Jeong Seon Yoon, Hyekyung Yang, Sang Hyun Sung & Young Choong Kim

  2. Institute for Life Science, Elcomscience Co. Ltd., San 56-1, Sillim-Dong, Gwanak-Gu, Seoul, 151-742, South Korea

    Seung Hyun Kim

Authors
  1. Jeong Seon Yoon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hyekyung Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Seung Hyun Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sang Hyun Sung
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Young Choong Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Young Choong Kim.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yoon, J.S., Yang, H., Kim, S.H. et al. Limonoids from Dictamnus dasycarpus Protect Against Glutamate-induced Toxicity in Primary Cultured Rat Cortical Cells. J Mol Neurosci 42, 9–16 (2010). https://doi.org/10.1007/s12031-010-9333-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-010-9333-1

Keywords

Search

Navigation