title: Brain-derived Neurotrophic Factor Signaling Mediates the Antidepressant-like Effect of the Total Flavonoids of Alpiniae Oxyphyllae Fructus in Chronic Unpredictable Mild Stress Mice.
abstract: The present study verified the antidepressant-like effects of the total flavonoids of Alpinia oxyphylla Miq. (AOF) using the chronic unpredictable mild stresses paradigm and explored the mechanism that underlies antidepressant-like effects of AOF in mice. Previous research has shown that tropomyosin-related kinase B (TrkB) receptor-mediated extracellular regulated protein kinases (ERK) signaling pathways participate in depression pathophysiology. Therefore, we aimed to explore whether AOF improved depression-like behaviors by increasing activity of ERK pathways mediated by TrkB. Results showed that AOF significantly reduced the immobility time in the forced swimming test and increased the sucrose preference in sucrose preference test. In addition, decreased phosphorylated cyclic adenosine monophosphate response element-binding protein (pCREB)/CREB, pERK/ERK, and pTrkB/TrkB levels in the hippocampus induced by chronic unpredictable mild stresses were reversed by intragastric administration of AOF. Results suggested that AOF increased pCREB/CREB, pERK/ERK, and pTrkB/TrkB levels by acting on the TrkB receptor. To verify this hypothesis, mice were pretreated with the TrkB inhibitor K252a (or 0.1% dimethyl sulfoxide, intraperitoneally, 2 weeks), before the intragastric administration of AOF. This resulted in an absence of antidepressant-like effects, as well as no activation of pERK/pCREB/BDNF signaling pathways. Results demonstrated that AOF might exert antidepressant-like effects by targeting TrkB receptor-mediated pERK/pCREB/BDNF signal systems, which could help to identify the AOF receptor. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, China.
authors.forename: Tingxu
authors.initials: T
authors.lastname: Yan
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wu
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, China.
authors.forename: Zheng-Zheng
authors.initials: ZZ
authors.lastname: Liao
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhao
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, China.
authors.forename: Kai-Shun
authors.initials: KS
authors.lastname: Bi
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jia
mesh_terms: D032429:Alpinia / Q000737:chemistry*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003863:Depression / Q000188:drug therapy*; D004195:Disease Models, Animal; D005419:Flavonoids / Q000494:pharmacology*; D008297:Male; D051379:Mice; D015398:Signal Transduction; D013315:Stress, Psychological
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D005419:Flavonoids; C579455:BDNF protein, human
keywords: Alpinia oxyphylla Miq; K252a; brain-derived neurotrophic factor (BDNF); chronic unpredictable mild stress (CUMS); depression; total flavonoids