Log in

Protection against hydrogen peroxide-induced injury by Z-ligustilide in PC12 cells

  • Research Article
  • Published:
Experimental Brain Research Aims and scope Submit manuscript

Abstract

Z-ligustilide (Z-LIG) is the primary lipophilic compound of the Chinese medicine Danggui (Radix Angelica sinensis). Previous studies demonstrated that Z-LIG had significant neuroprotective potential in both transient and permanent cerebral ischemia, possibly through antioxidant and anti-apoptotic mechanisms. The present study examined the mechanisms of Z-LIG on hydrogen peroxide (H2O2)-induced injury in PC12 cells. Following exposure of the cells to H2O2 (500 μM), a significant reduction in cell survival and total antioxidant capacity (TAC), as well as increased intracellular reactive oxygen species (ROS), were observed. In addition, H2O2 treatment significantly upregulated Bax expression, cleaved-caspase 3, and cytosolic cytochrome-c, and decreased Bcl-2 protein levels. Pretreatment of the cells with Z-LIG (0.1, 1.0, 2.5, or 5.0 μg/ml) significantly attenuated H2O2-induced cell death, attenuated increased intracellular ROS levels, and decreased Bax expression, cleaved-caspase 3, and cytochrome-c. Further, Z-LIG improved cellular TAC and concentration-dependently upregulated Bcl-2 expression. These results demonstrate that Z-LIG has a pronounced protective effect against H2O2-induced cytotoxicity, at least partly through improving cellular antioxidant defense and inhibiting the mitochondrial apoptotic pathway. These findings suggest that Z-LIG may be useful in the treatment of neurodegenerative disorders in which oxidative stress and apoptosis are mainly implicated.

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

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

  • Berker KI, Gueclue K, Tor I, Apak R (2007) Comparative evaluation of Fe (III) reducing power-based antioxidant capacity assays in the presence of phenanthroline, batho-phenanthroline (FRAP), and ferricyanide reagents. Talanta 72:1157–1165

    Article  CAS  PubMed  Google Scholar 

  • Bradford M (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  PubMed  CAS  Google Scholar 

  • Buttke TM, Sandstrom PA (1994) Oxidative stress as a mediator of apoptosis. Immunol Today 15:7–10

    Article  PubMed  CAS  Google Scholar 

  • Cheeseman KH (1993) Tissue injury by free radicals. Toxicol Ind Health 9:39–51

    PubMed  CAS  Google Scholar 

  • Delanty N, Dichter MA (2000) Antioxidant therapy in neurologic disease. Arch Neurol 57:1265–1270

    Article  PubMed  CAS  Google Scholar 

  • Du J, Bai B, Kuang X, Yu Y, Wang C, Ke Y, Xu Y, Tzang AH, Qian ZM (2006) Ligustilide inhibits spontaneous and agonists- or K+ depolarization-induced contraction of rat uterus. J Ethnopharmacol 108:54–58

    Article  PubMed  CAS  Google Scholar 

  • Du J, Yu Y, Ke Y, Wang C, Zhu L, Qian ZM (2007) Ligustilide attenuates pain behavior induced by acetic acid or formalin. J Ethnopharmacol 112:211–214

    Article  PubMed  CAS  Google Scholar 

  • Gilgun-Sherki Y, Rosenbaum Z, Melamed E, Offen D (2002) Antioxidant therapy in acute central nervous system injury: current state. Pharmacol Rev 54:271–284

    Article  PubMed  CAS  Google Scholar 

  • Götz ME, Künig G, Riederer P, Youdim MB (1994) Oxidative stress: free radical production in neuronal degeneration. Pharmacol Ther 63:37–122

    Article  PubMed  Google Scholar 

  • Halliwell B (1992) Reactive oxygen species and the central nervous system. J Neurochem 59:1609–1623

    Article  PubMed  CAS  Google Scholar 

  • Halliwell B, Gutteridge JMC, Cross CE (1992) Free radicals, antioxidants, and human disease: where are we now? J Lab Clin Med 119:598–620

    PubMed  CAS  Google Scholar 

  • Hu CY, Ding XL (2003) Extraction, isolation and structure identification of ligustilide from Angelica sinensis. J Wuxi Univ Light Ind 22:69–71

    CAS  Google Scholar 

  • Kuang X, Yao Y, Du JR, Liu YX, Wang CY, Qian ZM (2006) Neuroprotective role of Z-ligustilide against forebrain ischemic injury in ICR mice. Brain Res 1102:145–153

    Article  PubMed  CAS  Google Scholar 

  • Maroto R, Perez-Polo JR (1997) BCL-2-related protein expression in apoptosis: oxidative stress versus serum deprivation in PC12 cells. J Neurochem 69:514–523

    Article  PubMed  CAS  Google Scholar 

  • Matsumoto K, Kohno S, Ojima K, Tezuka Y, Kadota S, Watanabe H (1998) Effects of methylenechloride-soluble fraction of Japanese Angelica root extract, ligustilide and butylidenephthalide, on pentobarbital sleep in group-housed and socially isolated mice. Life Sci 62:2073–2082

    Article  PubMed  CAS  Google Scholar 

  • Peng HY, Du JR, Zhang GY, Kuang X, Liu YX, Qian ZM, Wang CY (2007) Neuroprotective effect of Z-ligustilide against permanent focal ischemic damage in rats. Biol Pharm Bull 30:309–312

    Article  PubMed  CAS  Google Scholar 

  • Pias EK, Aw TY (2002) Early redox imbalance mediates hydroperoxide-induced apoptosis in mitotic competent undifferentiated PC12 cells. Cell Death Differ 9:1007–1016

    Article  PubMed  CAS  Google Scholar 

  • Richardson JS, Subbarao KV, Ang LC (1992) On the possible role of iron-induced free radical peroxidation in neural degeneration in Alzheimer’s disease. Ann N Y Acad Sci 648:326–327

    Article  PubMed  CAS  Google Scholar 

  • Saito Y, Nishio K, Ogawa Y, Kinumi T, Yoshida Y, Masuo Y, Niki E (2007) Molecular mechanisms of 6-hydroxydopamine-induced cytotoxicity in PC12 cells: involvement of hydrogen peroxide-dependent and -independent action. Free Radic Biol Med 42:675–685

    Article  PubMed  CAS  Google Scholar 

  • Selkoe DJ (1994) Cell biology of the amyloid beta-protein precursor and the mechanism of Alzheimer’s disease. Annu Rev Cell Biol 10:373–403

    Article  PubMed  CAS  Google Scholar 

  • Sugawara T, Noshita N, Lewen A, Gashe Y, Ferrand-Drake M, Fujimura M, Morita-Fujimura Y, Chan PH (2002) Overexpression of copper/zinc superoxide dismutase in transgenic rats protects vulnerable neurons against ischemia damage by blocking the mitochondrial pathway of caspase activation. J Neurosci 22:209–217

    PubMed  CAS  Google Scholar 

  • Tao JY, Ruan YP, Mei QB, Liu S, Tian QL, Chen YZ, Zhang HD, Duan ZX (1984) Studies on the antiasthmatic action of ligustilide of dang-gui, Angelica sinensis (Oliv.) Diels. Acta Pharm Sin 19:561–565

    CAS  Google Scholar 

  • Tong L, Perez-Polo JR (1996) Effect of nerve growth factor on AP-1, NF-κB, and Oct DNA binding activity in apoptotic PC12 cells: extrinsic and intrinsic elements. J Neurosci Res 45:1–12

    Article  PubMed  CAS  Google Scholar 

  • Wong H, Joseph JA (1999) Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader. Free Radic Biol Med 27:612–616

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jun-Rong Du.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yu, Y., Du, JR., Wang, CY. et al. Protection against hydrogen peroxide-induced injury by Z-ligustilide in PC12 cells. Exp Brain Res 184, 307–312 (2008). https://doi.org/10.1007/s00221-007-1100-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00221-007-1100-3

Keywords

Navigation