Skip to main content
Log in

Protective effect of salidroside against H2O2-induced cell apoptosis in primary culture of rat hippocampal neurons

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Salidroside, a phenylpropanoid glycoside separated from a medicinal plant Rhodiola rosea, has been documented to have protective effects on neuronal cells in vitro. This study investigated whether salidroside was able to extend its unique neuroprotection to primary cultured rat hippocampal neurons against hydrogen peroxide (H2O2)-induced cell damage. Cell viability tests and cell apoptosis assays confirmed that salidroside pretreatment attenuated H2O2-stimulated apoptotic cell death in primary culture of hippocampal neurons in a concentration-dependent manner. The measurements of caspase-3 activity, nitric oxide (NO) production, and NO synthase (NOS) activity suggest that the protection of salidroside, shown in this study, might be mediated by inhibiting caspase-3 activity, and antagonizing NO production and NOS activity during H2O2 stimulation. Perhaps, this study might contribute to the development of salidroside as a broad-spectrum agent for preventing and/or treating neuronal damage in neurodegenerative disorders.

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
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Darbinyan V, Kteyan A, Panossian A et al (2000) Rhodiola rosea in stress induced fatigue-a double blind cross-over study of a standardized extract SHR-5 with a repeated low-dose regimen on the mental performance of healthy physicians during night duty. Phytomedicine 7:365–371

    PubMed  CAS  Google Scholar 

  2. Diaz Lanza AM, Abad Martinez MJ, Fernandez Matellano L et al (2001) Lignan and phenylpropanoid glycosides from Phillyrea latifolia and their in vitro anti-inflammatory activity. Planta Med 67:219–223

    Article  PubMed  CAS  Google Scholar 

  3. Iaremii IN, Grigor’eva NF (2002) Hepatoprotective properties of liquid extract of Rhodiola rosea. Eksp Klin Farmakol 65:57–59

    PubMed  CAS  Google Scholar 

  4. De Sanctis R, De Bellis R, Scesa C et al (2004) In vitro protective effect of Rhodiola rosea extract against hypochlorous acid-induced oxidative damage in human erythrocytes. Biofactors 20:147–159

    Article  PubMed  Google Scholar 

  5. Kanupriya, Prasad D, Sai Ram M et al (2005) Cytoprotective and antioxidant activity of Rhodiola imbricata against tert-butyl hydroperoxide induced oxidative injury in U-937 human macrophages. Mol Cell Biochem 275:1–6

    Article  PubMed  CAS  Google Scholar 

  6. Kucinskaite A, Briedis V, Savickas A (2004) Experimental analysis of therapeutic properties of Rhodiola rosea L. and its possible application in medicine. Medicina (Kaunas) 40:614–619

    Google Scholar 

  7. Ming DS, Hillhouse BJ, Guns ES et al (2005) Bioactive compounds from Rhodiola rosea (Crassulaceae). Phytother Res 19:740–743

    Article  PubMed  CAS  Google Scholar 

  8. Mattioli L, Perfumi M (2007) Rhodiola rosea L. extract reduces stress- and CRF-induced anorexia in rats. J Psychopharmacol 21:742–750

    Article  PubMed  Google Scholar 

  9. Perfumi M, Mattioli L (2007) Adaptogenic and central nervous system effects of single doses of 3% rosavin and 1% salidroside Rhodiola rosea L. extract in mice. Phytother Res 21:37–43

    Article  PubMed  CAS  Google Scholar 

  10. Zhang L, Yu HX, Sun Y et al (2007) Protective effects of salidroside on hydrogen peroxide-induced apoptosis in SH-SY5Y human neuroblastoma cells. Eur J Pharmacol 564:18–25

    Article  PubMed  CAS  Google Scholar 

  11. Yu S, Liu M, Gu X, Ding F (2008) Neuroprotective effects of salidroside in the PC12 cell model exposed to hypoglycemia and serum limitation. Cell Mol Neurobiol 28:1067–1078

    Article  PubMed  CAS  Google Scholar 

  12. Chen X, Liu J, Gu XS et al (2008) Salidroside attenuates glutamate-induced apoptotic cell death in primary cultured hippocampal neurons of rats. Brain Res 1238:189–198

    Article  PubMed  CAS  Google Scholar 

  13. Markesbery WR (1997) Oxidative stress hypothesis in Alzheimer’s disease. Free Radic Biol Med 23:134–147

    Article  PubMed  CAS  Google Scholar 

  14. Simonian NA, Coyle JT (1996) Oxidative stress in neurodegenerative diseases. Annu Rev Pharmacol Toxicol 36:83–106

    Article  PubMed  CAS  Google Scholar 

  15. Finkel T, Holbrook NJ (2000) Oxidants, oxidative stress and the biology of ageing. Nature 408:239–247

    Article  PubMed  CAS  Google Scholar 

  16. Choi J, Sullards MC, Olzmann JA et al (2006) Oxidative damage of DJ-1 is linked to sporadic Parkinson and Alzheimer diseases. J Biol Chem 281:10816–10824

    Article  PubMed  CAS  Google Scholar 

  17. Salvemini D, Cuzzocrea S (2002) Superoxide, superoxide dismutase and ischemic injury. Curr Opin Investing Drugs 3:886–895

    CAS  Google Scholar 

  18. Gilqun-Sherki Y, Rosenbaum Z, Melamed E et al (2002) Antioxidant therapy in acute central nervous system injury: current state. Pharmacol Rev 54:271–4284

    Article  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  20. Roedinger B, Armati PJ (2003) Oxidative stress induces axonal beading in cultured human brain tissue. Neurobiol Dis 13:222–229

    Article  CAS  Google Scholar 

  21. Ratan RR, Murphy TH, Baraban JM (1994) Oxidative stress induces apoptosis in embryonic cortical neurons. J Neurochem 62:376–379

    Article  PubMed  CAS  Google Scholar 

  22. Ishikawa Y, Satoh T, Enokido Y et al (1999) Generation of reactive oxygen species, release of l-glutamate and activation of caspases are required for oxygen-induced apoptosis of embryonic hippocampal neurons in culture. Brain Res 824:71–80

    Article  PubMed  CAS  Google Scholar 

  23. Ambrosio AF, Silva AP, Malva JO et al (2000) Role of desensitization of AMPA receptors on the neuronal viability and on the [Ca2+]i changes in cultured rat hippocampal neurons. Eur J NeuroSci 12:2021–2031

    Article  PubMed  CAS  Google Scholar 

  24. Liu H, Yang XL, Tanga R et al (2005) Effect of scutellarin on nitric oxide production in early stages of neuron damage induced by hydrogen peroxide. Pharmacological Res 51:205–210

    Article  CAS  Google Scholar 

  25. Chan PH (2001) Reactive oxygen radicals in signaling and damage in the ischemic brain. J Cereb Blood Flow Metab 21:2–14

    Article  PubMed  CAS  Google Scholar 

  26. Choi DW (1996) Ischemia-induced neuronal apoptosis. Curr Opin Neurobiol 6:667–672

    Article  PubMed  CAS  Google Scholar 

  27. Gorman AM, McGowan A, O’Neill C et al (1996) Oxidative stress and apoptosis in neurodegeneration. J Neurol Sci 139:45–52

    Article  PubMed  Google Scholar 

  28. Almli LM, Hamrick SE, Koshy AA et al (2001) Multiple pathways of neuroprotection against oxidative stress and excitotoxic injury in immature primary hippocampal neurons. Brain Res Dev Brain Res 132:121–129

    Article  PubMed  CAS  Google Scholar 

  29. Ni Y, Zhao B, Hou J et al (1996) Preventive effect of Ginkgo biloba extract on apoptosis in rat cerebellar neuronal cells induced by hydroxyl radicals. Neurosci Lett 214:115–118

    Article  PubMed  CAS  Google Scholar 

  30. Qiao L, Hanif R, Sphicas E et al (1998) Effect of aspirin on induction of apoptosis on HT-29 human colon adenocarcinoma cells. Biochem Pharmacol 55:53–64

    Article  PubMed  CAS  Google Scholar 

  31. Almeida RD, Manadas BJ, Melo CV et al (2005) Neuroprotection by BDNF against glutamate-induced apoptotic cell death is mediated by ERK and PI3-kinase pathways. Cell Death Differ 12:1329–1343

    Article  PubMed  CAS  Google Scholar 

  32. Degterev A, Boyce M, Yuan J (2003) A decade of caspases. Oncogene 22:8543–8567

    Article  PubMed  CAS  Google Scholar 

  33. Demelash A, Karlsson JO, Nilsson M et al (2004) Selenium has a protective role in caspase-3-dependent apoptosis induced by H2O2 in primary cultured pig thyrocytes. Eur J Endocrinol 150:841–849

    Article  PubMed  CAS  Google Scholar 

  34. Song JH, Slot AJ, Ryan RW et al (2004) Dopamine-induced death of PC12 cells is prevented by a substituted tetrahydronaphthalene. Neuropharmacology 46:984–993

    Article  PubMed  CAS  Google Scholar 

  35. Moncada S, Palmer RMJ, Higgs EA (1991) Nitric oxide: physiology, pathophysiology and pharmacology. Pharmacol Rev 43:109–142

    PubMed  CAS  Google Scholar 

  36. Mateo Ortega, Aleixandre AA (2000) Nitric oxide reactivity and mechanisms involved in its biological effects. Pharmacol Res 42:421–427

    Article  CAS  Google Scholar 

  37. Wiesinger H (2001) Arginine metabolism and the synthesis of nitric oxide in the nervous system. Prog Neurobiol 64:365–391

    Article  PubMed  CAS  Google Scholar 

  38. Togo T, Katsuse O, Iseki E (2004) Nitric oxide pathways in Alzheimer’s disease and other neurodegenerative dementias. Neurol Res 26:563–566

    Article  PubMed  CAS  Google Scholar 

  39. Sun J, Druhan LJ, Zweier JL (2008) Dose dependent effects of reactive oxygen and nitrogen species on the function of neuronal nitric oxide synthase. Arch Biochem Biophys 471:126–133

    Article  PubMed  CAS  Google Scholar 

  40. Avshalumov MV, Rice ME (2002) NMDA receptor activation mediates hydrogen peroxide-induced pathophysiology in rat hippocampal slices. J Neurophysiol 87:2896–2903

    PubMed  CAS  Google Scholar 

  41. Kurata K, Takebayashi M, Morinobu S, Yamawaki S (2004) β-estradiol, dehydroepiandrosterone, and dehydroepiandrosterone sulfate protect against N-Methyl-Daspartate-induced neurotoxicity in rat hippocampal neurons by different mechanisms. J Pharmacol Exp Ther 311:237–245

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by Hi-Tech Research and Development Program of China (973 Program, Grant No. 2003CB515306). We thank Professor Jie Liu for assistance in manuscript preparation.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Fei Ding.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, X., Zhang, Q., Cheng, Q. et al. Protective effect of salidroside against H2O2-induced cell apoptosis in primary culture of rat hippocampal neurons. Mol Cell Biochem 332, 85–93 (2009). https://doi.org/10.1007/s11010-009-0177-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-009-0177-3

Keywords

Navigation