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.
Similar content being viewed by others
References
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
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
Iaremii IN, Grigor’eva NF (2002) Hepatoprotective properties of liquid extract of Rhodiola rosea. Eksp Klin Farmakol 65:57–59
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
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
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
Ming DS, Hillhouse BJ, Guns ES et al (2005) Bioactive compounds from Rhodiola rosea (Crassulaceae). Phytother Res 19:740–743
Mattioli L, Perfumi M (2007) Rhodiola rosea L. extract reduces stress- and CRF-induced anorexia in rats. J Psychopharmacol 21:742–750
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
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
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
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
Markesbery WR (1997) Oxidative stress hypothesis in Alzheimer’s disease. Free Radic Biol Med 23:134–147
Simonian NA, Coyle JT (1996) Oxidative stress in neurodegenerative diseases. Annu Rev Pharmacol Toxicol 36:83–106
Finkel T, Holbrook NJ (2000) Oxidants, oxidative stress and the biology of ageing. Nature 408:239–247
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
Salvemini D, Cuzzocrea S (2002) Superoxide, superoxide dismutase and ischemic injury. Curr Opin Investing Drugs 3:886–895
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
Halliwell B (1992) Reactive oxygen species and the central nervous system. J Neurochem 59:1609–1623
Roedinger B, Armati PJ (2003) Oxidative stress induces axonal beading in cultured human brain tissue. Neurobiol Dis 13:222–229
Ratan RR, Murphy TH, Baraban JM (1994) Oxidative stress induces apoptosis in embryonic cortical neurons. J Neurochem 62:376–379
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
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
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
Chan PH (2001) Reactive oxygen radicals in signaling and damage in the ischemic brain. J Cereb Blood Flow Metab 21:2–14
Choi DW (1996) Ischemia-induced neuronal apoptosis. Curr Opin Neurobiol 6:667–672
Gorman AM, McGowan A, O’Neill C et al (1996) Oxidative stress and apoptosis in neurodegeneration. J Neurol Sci 139:45–52
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
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
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
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
Degterev A, Boyce M, Yuan J (2003) A decade of caspases. Oncogene 22:8543–8567
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
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
Moncada S, Palmer RMJ, Higgs EA (1991) Nitric oxide: physiology, pathophysiology and pharmacology. Pharmacol Rev 43:109–142
Mateo Ortega, Aleixandre AA (2000) Nitric oxide reactivity and mechanisms involved in its biological effects. Pharmacol Res 42:421–427
Wiesinger H (2001) Arginine metabolism and the synthesis of nitric oxide in the nervous system. Prog Neurobiol 64:365–391
Togo T, Katsuse O, Iseki E (2004) Nitric oxide pathways in Alzheimer’s disease and other neurodegenerative dementias. Neurol Res 26:563–566
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
Avshalumov MV, Rice ME (2002) NMDA receptor activation mediates hydrogen peroxide-induced pathophysiology in rat hippocampal slices. J Neurophysiol 87:2896–2903
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
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
Corresponding author
Rights 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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11010-009-0177-3