title: Macranthol promotes hippocampal neuronal proliferation in mice via BDNF-TrkB-PI3K/Akt signaling pathway.
abstract: Macranthol is a lignans natural product isolated from Illicium dunnianum Tutch. Our previous study has demonstrated that macranthol exerted an antidepressant-like effect in mice, at least in part, by increasing expression of hippocampal brain-derived neurotrophic factor (BDNF) expression. However, the relationship between macranthol and BDNF downstream signaling pathway in the hippocampus remains unknown. The aim of this present study was to explore the mechanism of macranthol-modulated BDNF signaling pathway in a depression-like model of chronic unpredictable mild stress. Our results found that pharmacological inhibition of tropomyosin related kinase B (TrkB) with K252a abolished the improvement of macranthol on sucrose preference and immobility time, and attenuated the stimulatory effect of macranthol on hippocampal BDNF and phospho-Akt. Furthermore, K252a also reversed the improvement of macranthol on hippocampal Bcl-2, caspase-3 expression and hippocampal neuronal cell proliferation. Therefore, our findings verify that macranthol-mediated antidepressant-like action is associated with BDNF-TrkB and downstream activation of PI3K/Akt-Bcl-2/caspase-3 signaling pathway.
authors.affiliation: Department of Chemical and Pharmaceutical Engineering, Huaqiao University, Xiamen 361021, Fujian Province, PR China.
authors.forename: Liu
authors.initials: L
authors.lastname: Luo
authors.affiliation: Department of Chemical and Pharmaceutical Engineering, Huaqiao University, Xiamen 361021, Fujian Province, PR China.
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Liu
authors.affiliation: Department of Chemical and Pharmaceutical Engineering, Huaqiao University, Xiamen 361021, Fujian Province, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Chemical and Pharmaceutical Engineering, Huaqiao University, Xiamen 361021, Fujian Province, PR China.
authors.forename: Rong-Hao
authors.initials: RH
authors.lastname: Mu
authors.affiliation: Department of Chemical and Pharmaceutical Engineering, Huaqiao University, Xiamen 361021, Fujian Province, PR China; Institute of Pharmaceutical Engineering, Huaqiao University, Xiamen 361021, Fujian Province, PR China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Chemical and Pharmaceutical Engineering, Huaqiao University, Xiamen 361021, Fujian Province, PR China; Institute of Pharmaceutical Engineering, Huaqiao University, Xiamen 361021, Fujian Province, PR China. Electronic address: litao.yi@yahoo.com.
authors.forename: Li-Tao
authors.initials: LT
authors.lastname: Yi
authors.affiliation: Department of Chemical and Pharmaceutical Engineering, Huaqiao University, Xiamen 361021, Fujian Province, PR China; Institute of Pharmaceutical Engineering, Huaqiao University, Xiamen 361021, Fujian Province, PR China. Electronic address: gengdi@hqu.edu.cn.
authors.forename: Di
authors.initials: D
authors.lastname: Geng
mesh_terms: D000475:Alkenes / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004347:Drug Interactions; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D026121:Indole Alkaloids / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009068:Movement / Q000187:drug effects; D009474:Neurons / Q000166:cytology* / Q000187:drug effects*; D010636:Phenols / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D020813:Receptor, trkB / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000475:Alkenes; D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D002227:Carbazoles; D026121:Indole Alkaloids; D010636:Phenols; D010750:Phosphoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; C531498:macranthol; C049985:staurosporine aglycone; D019869:Phosphatidylinositol 3-Kinases; D020813:Receptor, trkB; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D001973:Bromodeoxyuridine
keywords: Antidepressant; Brain-derived neurotrophic factor; K252a; Macranthol