Protective effects of salidroside on hydrogen peroxide-induced apoptosis in SH-SY5Y human neuroblastoma cells
ABSTRACT Oxidative stress plays an important role in Alzheimer's disease and other neurodegenerative disorders. Salidroside, a phenylpropanoid glycoside isolated from Rhodiola rosea L, shows potent antioxidant property. In this paper, the neuroprotective effects of salidroside on hydrogen peroxide (H2O2)-induced apoptosis in SH-SY5Y cells were investigated. Pretreatment with salidroside markedly attenuated H2O2-induced cell viability loss and apoptotic cell death in a dose-dependent manner. The mechanisms by which salidroside protected neuron cells from oxidative stress included the induction of several antioxidant enzymes, thioredoxin, heme oxygenase-1, and peroxiredoxin-I; the downregulation of pro-apoptotic gene Bax and the upregulation of anti-apoptotic genes Bcl-2 and Bcl-X(L). Furthermore, salidroside dose-dependently restored H2O2-induced loss of mitochondrial membrane potential as well as the elevation of intracellular calcium level. These results suggest that salidroside has protective effects against oxidative stress-induced cell apoptosis, which might be a potential therapeutic agent for treating or preventing neurodegenerative diseases implicated with oxidative stress.
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ABSTRACT: Gene expression profiling was performed on the human neuroglial cell line T98G after treatment with adaptogen ADAPT-232 and its constituents - extracts of Eleutherococcus senticosus root, Schisandra chinensis berry, and Rhodiola rosea root as well as several constituents individually, namely, eleutheroside E, schizandrin B, salidroside, triandrin, and tyrosol. A common feature for all tested adaptogens was their effect on G-protein-coupled receptor signaling pathways, i.e., cAMP, phospholipase C (PLC), and phosphatidylinositol signal transduction pathways. Adaptogens may reduce the cAMP level in brain cells by down-regulation of adenylate cyclase gene ADC2Y and up-regulation of phosphodiesterase gene PDE4D that is essential for energy homeostasis as well as for switching from catabolic to anabolic states and vice versa. Down-regulation of cAMP by adaptogens may decrease cAMP-dependent protein kinase A activity in various cells resulting in inhibition stress-induced catabolic transformations and saving of ATP for many ATP-dependant metabolic transformations. All tested adaptogens up-regulated the PLCB1 gene, which encodes phosphoinositide-specific PLC and phosphatidylinositol 3-kinases (PI3Ks), key players for the regulation of NF-κB-mediated defense responses. Other common targets of adaptogens included genes encoding ERα estrogen receptor (2.9-22.6 fold down-regulation), cholesterol ester transfer protein (5.1-10.6 fold down-regulation), heat shock protein Hsp70 (3.0-45.0 fold up-regulation), serpin peptidase inhibitor (neuroserpin), and 5-HT3 receptor of serotonin (2.2-6.6 fold down-regulation). These findings can be reconciled with the observed beneficial effects of adaptogens in behavioral, mental, and aging-associated disorders. Combining two or more active substances in one mixture significantly changes deregulated genes profiles: synergetic interactions result in activation of genes that none of the individual substances affected, while antagonistic interactions result in suppression some genes activated by individual substances. These interactions can have an influence on transcriptional control of metabolic regulation both on the cellular level and the level of the whole organism. Merging of deregulated genes array profiles and intracellular networks is specific to the new substance with unique pharmacological characteristics. Presumably, this phenomenon could be used to eliminate undesirable effects (e.g., toxic effects) and increase the selectivity of pharmacological intervention.Frontiers in Neuroscience 02/2013; 7:16. DOI:10.3389/fnins.2013.00016
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ABSTRACT: A novel pH-responsive nano-carrier MSNs-PAA, possessing mesoporous silica nanoparticles (MSNs) cores and poly(acrylic acid) (PAA) shell-layers, was developed for controlled release of salidroside. The vinyl double bonds modified MSNs were synthesized by using cetyltrimethylammonium bromide (CTAB) as templates, tetraethyl orthosilicate (TEOS) as silicon source, and 3-(trimethoxylsilyl) propyl methacrylate (MPS) as surface modification functionalities. The pH-responsive layers of PAA were grafted onto the vinyl double bonds of the MSNs via precipitation polymerization, producing the MSNs-PAA with a hollow cubic core and mesoporous shell with penetrating pore channels. The characteristic results also showed that PAA was successfully grafted onto the surface of the MSNs. The MSNs-PAA was investigated as carriers for loading and regulating the release of salidroside in different pH solutions for the first time. The results demonstrated that the PAA layers on the surface of MSNs-PAA exhibited opened and closed states at different pH values, and thus could regulate the uptake and release of salidroside. The application of such pH-responsive nano-carrier might offer a potential platform for controlled delivery and increasing the bioavailability of drugs.International Journal of Pharmaceutics 02/2013; 446(1-2). DOI:10.1016/j.ijpharm.2013.01.071 · 3.79 Impact Factor
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ABSTRACT: Oxidative stress plays an important role in the development of various human diseases. Aqueous chamomile extract is used as herbal medicine, in the form of tea, demonstrated to possess antiinflammatory and antioxidant properties. We demonstrate the cytoprotective effects of chamomile on hydrogen peroxide (H(2) O(2) )-induced cellular damage in macrophage RAW 264.7 cells. Pretreatment of cells with chamomile markedly attenuated H(2) O(2) -induced cell viability loss in a dose-dependent manner. The mechanisms by which chamomile-protected macrophages from oxidative stress was through the induction of several antioxidant enzymes including NAD(P)H:quinone oxidoreductase, superoxide dismutase, and catalase and increase nuclear accumulation of the transcription factor Nrf2 and its binding to antioxidant response elements. Furthermore, chamomile dose-dependently reduced H(2) O(2) -mediated increase in the intracellular levels of reactive oxygen species. Our results, for the first time, demonstrate that chamomile has protective effects against oxidative stress and might be beneficial to provide defense against cellular damage. Copyright © 2012 John Wiley & Sons, Ltd.Phytotherapy Research 01/2013; 27(1). DOI:10.1002/ptr.4701 · 2.40 Impact Factor