Neuroprotective Effects of Salidroside in the PC12 Cell Model Exposed to Hypoglycemia and Serum Limitation
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The hypoglycemia and serum limitation-induced cell death in cultured PC12 cells represents a useful in vitro model for the study of brain ischemia and neurodegenerative disorders. Salidroside is a phenylpropanoid glycoside isolated from Rhodiola rosea L., a traditional Chinese medicinal plant, and has displayed a broad spectrum of pharmacological properties. In this study, MTT assay, Hoechst 33342 staining, and flow cytometry with annexin V/PI staining collectively showed that pretreatment with salidroside attenuated, in a dose-dependent manner, cell viability loss, and apoptotic cell death in cultured PC12 cells induced by hypoglycemia and serum limitation. RT-PCR, Western blot analysis, and enzymatic colorimetric assay indicated the changes in expression levels of Bcl-2, Bax, and caspase3 in PC12 cells on exposure to hypoglycemia and serum limitation with and without salidroside pretreatment, respectively. Rhodamine 123 staining and flow cytometry with 2′,7′-Dichlorofluorescin diacetate staining revealed the changes in the mitochondrial membrane potential and radical oxygen species (ROS) production in PC12 cells on exposure to hypoglycemia and serum limitation with and without salidroside pretreatment, respectively. The experimental results suggest that salidroside protects the PC12 cells against hypoglycemia and serum limitation-induced cytotoxicity possibly by the way of the modulation of apoptosis-related gene expression, the restoration of the mitochondrial membrane potential, and the inhibition of the intracellular ROS production. Our findings might raise a possibility of potential therapeutic applications of salidroside for preventing and treating cerebral ischemic and neurodegenerative diseases.
KeywordsSalidroside Hypoglycemia and serum limitation Apoptosis PC12 cells Neuroprotection
This study was supported by Hi-Tech Research and Development Program of China (973 Program, Grant no. 2003CB515306). We wish to thank Professor Jie Liu for assistance in the preparation of the manuscript.
- Darbinyan V, Kteyan A, Panossian A, Gabrielian E, Wikman G, Wagner H (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 7:365–371PubMedGoogle Scholar
- Kucinskaite A, Briedis V, Savickas A (2004) Experimental analysis of therapeutic properties of Rhodiola rosea L. and its possible application in medicine. Medicina (Kaunas) 40:614–619Google Scholar
- Oliver CN, Starke-Reed PE, Stadtman ER, Liu GJ, Carney JM, Floyd RA (1990) Oxidative damage to brain proteins, loss of glutamine synthetase activity, and production of free radicals during ischemia/reperfusion-induced injury to gerbil brain. Proc Natl Acad Sci USA 87:5144–5147PubMedCrossRefGoogle Scholar
- Petkov VD, Yonkov D, Mosharoff A, Kambourova T, Alova L, Petkov VV, Todorov I (1986) Effects of alcohol aqueous extract from Rhodiola rosea L. roots on learning and memory. Acta Physiol Pharmacol Bulg 12:3–16Google Scholar
- Woronowicz A, Amith SR, Davis VW, Jayanth P, De Vusser K, Laroy W, Contreras R, Meakin SO, Szewczuk MR (2007) Trypanosome trans-sialidase mediates neuroprotection against oxidative stress, serum/glucose deprivation, and hypoxia-induced neurite retraction in Trk-expressing PC12 cells. Glycobiology 17(7):725–734PubMedCrossRefGoogle Scholar