title: Effect of Tenuifoliside A isolated from Polygala tenuifolia on the ERK and PI3K pathways in C6 glioma cells.
abstract: 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caused the enhanced phosphorylation of cyclic AMP response element binding protein (CREB) at Ser133 site, the effect was revoked by U0126, LY294002 and K252a.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.
authors.affiliation: Department of Clinical Pharmacology, Chinese PLA General Hospital, Beijing 100853, China. Electronic address: dongxianzhe301@163.com.
authors.forename: Xian-zhe
authors.initials: XZ
authors.lastname: Dong
authors.affiliation: Department of Clinical Pharmacology, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Cui-li
authors.initials: CL
authors.lastname: Huang
authors.affiliation: Department of Clinical Pharmacology, Chinese PLA General Hospital, Beijing 100853, China; Department of Pharmacy, Hebei North University, Zhangjiakou 075000, China.
authors.forename: Bing-ying
authors.initials: BY
authors.lastname: Yu
authors.affiliation: Department of Clinical Pharmacology, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Clinical Pharmacology, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Li-hua
authors.initials: LH
authors.lastname: Mu
authors.affiliation: Department of Clinical Pharmacology, Chinese PLA General Hospital, Beijing 100853, China. Electronic address: cpi301@163.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000187:drug effects; D002070:Butadienes / Q000494:pharmacology; D050882:CREB-Binding Protein / Q000037:antagonists & inhibitors / Q000187:drug effects; D002227:Carbazoles / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D004186:Disaccharidases / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D026121:Indole Alkaloids / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008954:Models, Biological; D009025:Morpholines / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D018517:Plant Roots / Q000737:chemistry; D031801:Polygala / Q000737:chemistry*; D051381:Rats; D020813:Receptor, trkB / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002070:Butadienes; D050882:CREB-Binding Protein; D002227:Carbazoles; D002867:Chromones; D004186:Disaccharidases; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; D009025:Morpholines; D009570:Nitriles; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020813:Receptor, trkB; C113580:U 0126; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C049985:staurosporine aglycone; C494365:Crebbp protein, rat; C000589515:tenuifoliside A
keywords: C6 glioma cells; PI3K pathways; Polygala tenuifolia