title: Synergistic Neuroprotective Effects of Two Herbal Ingredients via CREB-Dependent Pathway.
abstract: As two natural oligosaccharide esters, 3,6'-Disinapoyl sucrose (DISS) and tenuifolisideA (TFSA) are originating from the root ofPolygala tenuifoliaWilld, a traditional Chinese medicine used in treatment of mental disorders. Previous reports have shown that both of them possessin vitroneuroprotective 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.
authors.affiliation: Department of Clinical Pharmacology and Pharmacy, Pharmacy Care Center, Chinese PLA General Hospital Beijing, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Clinical Pharmacology and Pharmacy, Pharmacy Care Center, Chinese PLA General Hospital Beijing, China.
authors.forename: Dongxiao
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Clinical Pharmacology and Pharmacy, Pharmacy Care Center, Chinese PLA General Hospital Beijing, China.
authors.forename: Runqing
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Department of Clinical Pharmacology and Pharmacy, Pharmacy Care Center, Chinese PLA General Hospital Beijing, China.
authors.forename: Xianzhe
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Clinical Pharmacology and Pharmacy, Pharmacy Care Center, Chinese PLA General Hospital Beijing, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Clinical Pharmacology and Pharmacy, Pharmacy Care Center, Chinese PLA General Hospital Beijing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
keywords: CREB; DISS; TFSA; neuroprotective effect; synergistic effect