J Mol Neurosci. 2014 Aug;53(4):600-7.
|Neuroprotective effects of 3,6'-disinapoyl sucrose through increased BDNF levels and CREB phosphorylation via the CaMKII and ERK1/2 pathway.[Pubmed: 24488601]|
| 3,6'-Disinapoyl sucrose can have neuroprotective effects and antidepressive activity in rats, at least in part, by increased expression of cyclic AMP response element (CRE)-binding protein (CREB) and its downstream target protein, brain-derived neurotrophic factor (BDNF). The aim of the present study was to explore the mechanism of 3,6'-Disinapoyl sucrose-modulated BDNF and CREB expression. In this study, we confirmed its neuroprotective effect by showing that 3,6'-Disinapoyl sucrose, at concentrations above 30 μM, could promote the neuron cell viability and protected the glutamate and H2O2-induced toxicity in the human neuroblastoma (SH-SY5Y) cell line. 3,6'-Disinapoyl sucrose treatment also increased acute (from 15 to 30 min) BDNF expression and CREB phosphorylation in a dose-dependent manner. Pharmacological inhibition of mitogen-activated protein kinase 1 (ERK1/2), CaMKII, and Trk (with U0126, KN93, or K252a, respectively) partially attenuated the stimulatory effect of 3,6'-Disinapoyl sucrose on phospho-CREB and BDNF expression; however, it was not inhibited by pharmacological inhibition of PKA or PI3K (with H89 and LY294002, respectively). The results are consistent with the effects of 3,6'-Disinapoyl sucrose on CRE-directed gene transcription, as U0126 and KN-93 treatment also blocked the 3,6'-Disinapoyl sucrose-induced expression of the CRE-luciferase reporter gene. The results from the present study suggest that 3,6'-Disinapoyl sucrose-mediated regulation of BDNF gene expression is associated with CREB-mediated transcription of BDNF and upstream activation of ERK1/2 and CaMKII. Finally, 3,6'-Disinapoyl sucrose may exert neuroprotective and antidepressant effects through these signaling pathways in neuronal cells.
J Biomed Biotechnol. 2012;2012:1-5.
|Protection of SH-SY5Y neuronal cells from glutamate-induced apoptosis by 3,6'-disinapoyl sucrose, a bioactive compound isolated from Radix Polygala.[Pubmed: 21836813]|
|The neuroprotective effects of 3,6'-Disinapoyl sucrose (DISS) from Radix Polygala against glutamate-induced SH-SY5Y neuronal cells injury were evaluated in the present study. SH-SY5Y neuronal cells were pretreated with glutamate (8 mM) for 30 min followed by cotreatment with 3,6'-Disinapoyl sucrose for 12 h. Cell viability was determined by (3,4,5-dimethylthiazol-2-yl)-2,5-diphenylte-trazolium bromide (MTT) assay, and apoptosis was confirmed by cell morphology and flow cytometry assay, evaluated with propidium iodide dye. Treatment with 3,6'-Disinapoyl sucrose (0.6, 6, and 60 μmol/L) increased cell viability dose dependently, inhibited LDH release, and attenuated apoptosis. The mechanisms by which 3,6'-Disinapoyl sucrose protected neuron cells from glutamate-induced excitotoxicity included the downregulation of proapoptotic gene Bax and the upregulation of antiapoptotic gene Bcl-2. The present findings indicated that 3,6'-Disinapoyl sucrose exerts neuroprotective effects against glutamate toxicity, which might be of importance and contribute to its clinical efficacy for the treatment of neurodegenerative diseases.
J Pharm Pharmacol. 2011 Jun;63(6):869-74.
|Possible mechanism of the antidepressant effect of 3,6'-disinapoyl sucrose from Polygala tenuifolia Willd.[Pubmed: 21585386]|
The present study was designed to observe the effects of 3,6'-Disinapoyl sucrose (DISS), an active oligosaccharide ester component obtained from the roots of Polygala tenuifolia Willd., on behavioral and biochemical aspects of depression induced by chronic mild stress (CMS) in rats. It is the first exploration of the possible association between 3,6'-Disinapoyl sucrose's antidepressant-like effects and biochemical markers of depression, and involved measuring monoamine oxidase (MAO) activity, cortisol levels, superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels.
Rats were exposed to stressor once daily for consecutive 5 weeks. 3,6'-Disinapoyl sucrose and a positive control drug, fluoxetine, were administered via gastric intubation to once daily for consecutive 3 weeks from the third week.
The results showed that rats subjected to CMS exhibit a reduction in sucrose intake. Conversely, brain MAO-A and MAO-B activity, plasma cortisol levels, and MDA levels were increased, while SOD activity was decreased following CMS exposures. DISS significantly inhibited MAO-A and MAO-B activity and blocked plasma elevated cortisol level, an indicator of the hypothalamic-pituitary-adrenal (HPA) axis. In addition, DISS increases SOD activity, inhibits lipid peroxidation, and lessens production of MDA.
These results suggest that 3,6'-Disinapoyl sucrose may possess potent and rapid antidepressant properties, which are mediated via MAO, the HPA axis and oxidative systems. These antidepressant actions make 3,6'-Disinapoyl sucrose a potentially valuable drug for the treatment of depression.
Neurochem Int. 2010 Feb;56(3):461-5.
|Antidepressant-like effects of 3,6'-disinapoyl sucrose on hippocampal neuronal plasticity and neurotrophic signal pathway in chronically mild stressed rats.[Pubmed: 20018220]|
|Recent studies suggest that the behavioral effects of chronic antidepressant treatment are mediated by stimulation of hippocampal neuronal plasticity and neurogenesis. The present study was designed to examine the effects of 3,6'-Disinapoyl sucrose (DISS), a bioactive component of Polygala tenuifolia Willd, on the expressions of four plasticity-associated genes: cell adhesion molecule L1 (CAM-L1), laminin, cAMP response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in hippocampus, all of which are involved in neuronal plasticity and neurite outgrowth. We confirmed that chronic stress in rats caused a reduction in sensitivity to reward (sucrose consumption) and a decrease in mRNA levels of CAM-L1, laminin, and BDNF, together with a decrease in protein levels of phosphorylated CREB and BDNF. Repeated administration of 3,6'-Disinapoyl sucrose for 21 days at doses of 5, 10 and 20mg/kg reversed stress-induced alterations in sucrose consumption and these target mRNA and protein levels. In conclusion, increased expressions in the hippocampus of three noradrenergic-regulated plasticity genes and one neurotrophic factor may be one of the molecular and cellular mechanisms underlying the antidepressant action of 3,6'-Disinapoyl sucrose in chronic mild stress (CMS) rats.