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Synergistic Neuroprotective Effects of Two Herbal Ingredients via CREB-Dependent Pathway

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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.

No MeSH data available.


Combination effect of DISS and TFSA on levels of tNOS and iNOS in SY5Y cells (n = 18). SY5Y cells were exposed to Glu for 24 h, after which Glu was changed to DISS and TFSA combination medium for 48 h. Levels of tNOS and iNOS were determined by a reagent kit ∗∗p < 0.01 compared with Glu; ∗∗p < 0.01 compared with the control; ∗p < 0.05, #p < 0.01 compared with its compound alone.
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Figure 5: Combination effect of DISS and TFSA on levels of tNOS and iNOS in SY5Y cells (n = 18). SY5Y cells were exposed to Glu for 24 h, after which Glu was changed to DISS and TFSA combination medium for 48 h. Levels of tNOS and iNOS were determined by a reagent kit ∗∗p < 0.01 compared with Glu; ∗∗p < 0.01 compared with the control; ∗p < 0.05, #p < 0.01 compared with its compound alone.

Mentions: To further investigate the additive neuroprotection of DISS and TFSA against the Glu-induced cell injury, we examined the levels of tNOS and iNOS, which play an important role in cell apoptosis or neurodegenerative disorders (Chen et al., 2016; Zhu et al., 2016). Figure 5 shows that Glu significantly increased the levels of tNOS and iNOS. DISS or TFSA treatment alone decreased the intracellular level of tNOS by 4–8%, but showed no effect on iNOS level. However, co-treatment of DISS and TFSA significantly decreased such an elevation of tNOS and iNOS levels by 29.3 and 40.5%, respectively. These results suggested that the combination of DISS and TFSA could more vigorously inhibit the Glu-induced NO overproduction.


Synergistic Neuroprotective Effects of Two Herbal Ingredients via CREB-Dependent Pathway
Combination effect of DISS and TFSA on levels of tNOS and iNOS in SY5Y cells (n = 18). SY5Y cells were exposed to Glu for 24 h, after which Glu was changed to DISS and TFSA combination medium for 48 h. Levels of tNOS and iNOS were determined by a reagent kit ∗∗p < 0.01 compared with Glu; ∗∗p < 0.01 compared with the control; ∗p < 0.05, #p < 0.01 compared with its compound alone.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC5037165&req=5

Figure 5: Combination effect of DISS and TFSA on levels of tNOS and iNOS in SY5Y cells (n = 18). SY5Y cells were exposed to Glu for 24 h, after which Glu was changed to DISS and TFSA combination medium for 48 h. Levels of tNOS and iNOS were determined by a reagent kit ∗∗p < 0.01 compared with Glu; ∗∗p < 0.01 compared with the control; ∗p < 0.05, #p < 0.01 compared with its compound alone.
Mentions: To further investigate the additive neuroprotection of DISS and TFSA against the Glu-induced cell injury, we examined the levels of tNOS and iNOS, which play an important role in cell apoptosis or neurodegenerative disorders (Chen et al., 2016; Zhu et al., 2016). Figure 5 shows that Glu significantly increased the levels of tNOS and iNOS. DISS or TFSA treatment alone decreased the intracellular level of tNOS by 4–8%, but showed no effect on iNOS level. However, co-treatment of DISS and TFSA significantly decreased such an elevation of tNOS and iNOS levels by 29.3 and 40.5%, respectively. These results suggested that the combination of DISS and TFSA could more vigorously inhibit the Glu-induced NO overproduction.

View Article: PubMed Central - PubMed

ABSTRACT

As two natural oligosaccharide esters, 3,6&rsquo;-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.

No MeSH data available.