PMID- 24877714 OWN - NLM STAT- MEDLINE DCOM- 20150420 LR - 20191210 IS - 1618-095X (Electronic) IS - 0944-7113 (Linking) VI - 21 IP - 10 DP - 2014 Sep 15 TI - Effect of Tenuifoliside A isolated from Polygala tenuifolia on the ERK and PI3K pathways in C6 glioma cells. PG - 1178-88 LID - S0944-7113(14)00206-2 [pii] LID - 10.1016/j.phymed.2014.04.022 [doi] AB - Tenuifoliside A (TFSA) is a bioactive oligosaccharide ester component of Polygala tenuifolia Wild, a traditional Chinese medicine which was used to manage mental disorders effectively. The neuroprotective and anti-apoptotic effects of TFSA have been demonstrated in our previous studies. The present work was designed to study the molecular mechanism of TFSA on promoting the viability of rat glioma cells C6. We exposed C6 cells to TFSA (or combined with ERK, PI3K and TrkB inhibitors) to examine the effects of TFSA on the cell viability and the expression and phosphorylation of key proteins in the ERK and PI3K signaling pathway. TFSA increased levels of phospho-ERK and phospho-Akt, enhanced release of BDNF, which were blocked by ERK and PI3K inhibitors, respectively (U0126 and LY294002). Moreover, the TFSA caused the enhanced phosphorylation of cyclic AMP response element binding protein (CREB) at Ser133 site, the effect was revoked by U0126, LY294002 and K252a. Furthermore, when C6 cells were pretreated with K252a, a TrkB antagonist, known to significantly inhibit the activity of brain-derived neurotrophic factor (BDNF), blocked the levels of phospho-ERK, phospho-Akt and phosphor-CREB. Taking these results together, we suggested the neuroprotection of TFSA might be mediated through BDNF/TrkB-ERK/PI3K-CREB signaling pathway in C6 glioma cells. CI - Copyright (c) 2014 Elsevier GmbH. All rights reserved. FAU - Dong, Xian-zhe AU - Dong XZ AD - Department of Clinical Pharmacology, Chinese PLA General Hospital, Beijing 100853, China. Electronic address: dongxianzhe301@163.com. FAU - Huang, Cui-li AU - Huang CL AD - Department of Clinical Pharmacology, Chinese PLA General Hospital, Beijing 100853, China. FAU - Yu, Bing-ying AU - Yu BY AD - Department of Clinical Pharmacology, Chinese PLA General Hospital, Beijing 100853, China; Department of Pharmacy, Hebei North University, Zhangjiakou 075000, China. FAU - Hu, Yuan AU - Hu Y AD - Department of Clinical Pharmacology, Chinese PLA General Hospital, Beijing 100853, China. FAU - Mu, Li-hua AU - Mu LH AD - Department of Clinical Pharmacology, Chinese PLA General Hospital, Beijing 100853, China. FAU - Liu, Ping AU - Liu P AD - Department of Clinical Pharmacology, Chinese PLA General Hospital, Beijing 100853, China. Electronic address: cpi301@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140528 PL - Germany TA - Phytomedicine JT - Phytomedicine : international journal of phytotherapy and phytopharmacology JID - 9438794 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Butadienes) RN - 0 (Carbazoles) RN - 0 (Chromones) RN - 0 (Drugs, Chinese Herbal) RN - 0 (Enzyme Inhibitors) RN - 0 (Indole Alkaloids) RN - 0 (Morpholines) RN - 0 (Nitriles) RN - 0 (Phosphoinositide-3 Kinase Inhibitors) RN - 0 (U 0126) RN - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one) RN - 97161-97-2 (staurosporine aglycone) RN - EC 2.3.1.48 (CREB-Binding Protein) RN - EC 2.3.1.48 (Crebbp protein, rat) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 3.2.1.- (Disaccharidases) RN - S36S8L9Y70 (tenuifoliside A) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/drug effects MH - Butadienes/pharmacology MH - CREB-Binding Protein/antagonists & inhibitors/drug effects MH - Carbazoles/pharmacology MH - Cell Line, Tumor MH - Cell Proliferation/drug effects MH - Cell Survival/drug effects MH - Chromones/pharmacology MH - Disaccharidases/chemistry/isolation & purification/*pharmacology MH - Drugs, Chinese Herbal/chemistry/isolation & purification/*pharmacology MH - Enzyme Inhibitors/pharmacology MH - Indole Alkaloids/pharmacology MH - MAP Kinase Signaling System/*drug effects MH - Models, Biological MH - Morpholines/pharmacology MH - Nitriles/pharmacology MH - Phosphatidylinositol 3-Kinases/*drug effects MH - Phosphoinositide-3 Kinase Inhibitors MH - Phosphorylation/drug effects MH - Plant Roots/chemistry MH - Polygala/*chemistry MH - Rats MH - Receptor, trkB/drug effects MH - Signal Transduction/*drug effects OTO - NOTNLM OT - C6 glioma cells OT - PI3K pathways OT - Polygala tenuifolia EDAT- 2014/06/01 06:00 MHDA- 2015/04/22 06:00 CRDT- 2014/06/01 06:00 PHST- 2013/10/30 00:00 [received] PHST- 2014/03/04 00:00 [revised] PHST- 2014/04/20 00:00 [accepted] PHST- 2014/06/01 06:00 [entrez] PHST- 2014/06/01 06:00 [pubmed] PHST- 2015/04/22 06:00 [medline] AID - S0944-7113(14)00206-2 [pii] AID - 10.1016/j.phymed.2014.04.022 [doi] PST - ppublish SO - Phytomedicine. 2014 Sep 15;21(10):1178-88. doi: 10.1016/j.phymed.2014.04.022. Epub 2014 May 28.