Abstract
As two natural oligosaccharide esters, 3,6’-Disinapoyl sucrose (DISS) and tenuifolisideA (TFSA) are originating from the root of Polygala tenuifolia Willd, a traditional Chinese medicine used in treatment of mental disorders. Previous reports have shown that both of them possess in vitro neuroprotective effects by stimulating different upstream pathways related with cyclic AMP-responsive element-binding protein (CREB). In the present study, we investigated the additive neuroprotective effects of DISS and TFSA on Glu-induced damage of SY5Y cells and purposed the possible underlying mechanism. The interaction between DISS and TFSA showed a clear-cut synergistic effect as evidenced by combination index (CI). Additional evidence from biochemical (NOS activity) assays confirmed their additive inhibition on the Glu-induced NOS hyperactivation. Moreover, we showed that co-treatment of DISS and TFSA resulted in an additively up-regulated phosphorylation of CREB as well as increased expressions of CRTC1 and BDNF. Neuroprotective effects of DISS and TFSA on Glu-induced decrease in cell viability were blocked by MAPK/ERK1/2 inhibitor (U0126) and PI3-K inhibitor (LY290042). Nevertheless, the CRTC1 or BDNF expression induced by these two compounds was significantly reduced in the presence of either ERK or PI3-K inhibitor, indicating that the two oligosaccharide esters shared some common pathways in the regulation of CREB-BDNF pathway. Taken together, we, for the first time, showed that DISS and TFSA exerted the additive neuroprotective effects on CREB-BDNF signaling pathway through complementary mechanisms.
Highlights
As a common mental disorder, depression is estimated to affect 350 million people in the world by 2030 (Mathers et al, 2008)
We investigated whether the combination of Disinapoyl sucrose (DISS) and TFSA could have an additive or synergistic effect in preventing neuronal damage in SH-SY5Y cells
In order to lower the possible side effects of the compounds according to our previous experience, the concentrations of DISS and TFSA were set to 150/75 μM and 75/50 μM, respectively
Summary
As a common mental disorder, depression is estimated to affect 350 million people in the world by 2030 (Mathers et al, 2008). 3,6’-Disinapoyl sucrose (DISS) and tenuifoliside A (TFSA) are the principle active ingredients in the extract of Radix Polygalae. Our previous studies have indicated that both of DISS and TFSA have neuroprotective effects in different in vitro models (Hu et al, 2010, 2011, 2012). Both can stimulate the expression and phosphorylation of key proteins in the Synergistic Effects of DISS and TFSA cAMP response element-binding protein (CREB) signaling pathway (Liu et al, 2010; Dong et al, 2014)
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