title: GC-MS-based metabolomic study on the antidepressant-like effects of diterpene ginkgolides in mouse hippocampus.
abstract: Ginkgo biloba extract (GBE), including EGb-761, have been suggested to have antidepressant activity based on previous behavioral and biochemical analyses. However, because GBE contain many constituents, the mechanisms underlying this suggested antidepressant activity are unclear. Here, we investigated the antidepressant-like effects of diterpene ginkgolides (DG), an important class of constituents in GBE, and studied their effects in the mouse hippocampus using a GC-MS-based metabolomics approach. Mice were randomly divided into five groups and injected daily until testing with 0.9% NaCl solution, one of three doses of DG (4.06, 12.18, and 36.54mg/kg), or venlafaxine. Sucrose preference (SPT) and tail suspension (TST) tests were then performed to evaluate depressive-like behaviors in mice. DG (12.18 and 36.54mg/kg) and venlafaxine (VLX) administration significantly increased hedonic behavior in mice in the SPT. DG (12.18mg/kg) treatment also shortened immobility time in the TST, suggestive of antidepressant-like effects. Significant differences in the metabolic profile in the DG (12.18mg/kg) compared with the control or VLX group indicative of an antidepressant-like effect were observed using multivariate analysis. Eighteen differential hippocampal metabolites were identified that discriminated the DG (12.18mg/kg) and control groups. These biochemical changes involved neurotransmitter metabolism, oxidative stress, glutathione metabolism, lipid metabolism, energy metabolism, and kynurenic acid, providing clues to the therapeutic mechanisms of DG. Thus, this study showed that DG has antidepressant-like activities in mice and shed light on the biological mechanisms underlying the effects of diterpene ginkgolides on behavior, providing an important drug candidate for the treatment of depression.
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurobiology, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; Department of Neurology, The Inner Mongolia Autonomous Region people's Hospital, Hohhot, Inner Mongolia, China.
authors: Zihong
authors: Z
authors: Liang
authors: Chongqing Key Laboratory of Neurobiology, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, China.
authors: Shunjie
authors: S
authors: Bai
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurobiology, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors: Peng
authors: P
authors: Shen
authors: Chongqing Key Laboratory of Neurobiology, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, China.
authors: Qingchuan
authors: Q
authors: Hu
authors: Chongqing Key Laboratory of Neurobiology, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing, China.
authors: Xingfa
authors: X
authors: Wang
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurobiology, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors: Meixue
authors: M
authors: Dong
authors: Chongqing Key Laboratory of Neurobiology, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing, China.
authors: Wei
authors: W
authors: Wang
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurobiology, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors: Juan
authors: J
authors: Li
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurobiology, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors: Ke
authors: K
authors: Cheng
authors: Chongqing Key Laboratory of Neurobiology, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, China.
authors: Shuxiao
authors: S
authors: Zhang
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurobiology, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors: Dezhi
authors: D
authors: Zou
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurobiology, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors: Yu
authors: Y
authors: Han
authors: Chongqing Key Laboratory of Neurobiology, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors: Haiyang
authors: H
authors: Wang
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurobiology, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing, China. Electronic address: xiepeng@cqmu.edu.cn.
authors: Peng
authors: P
authors: Xie
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D003863:Depression / Q000188:drug therapy*; D008401:Gas Chromatography-Mass Spectrometry; D020441:Ginkgo biloba; D046934:Ginkgolides / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D055432:Metabolomics / Q000379:methods; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology; D000069470:Venlafaxine Hydrochloride / Q000494:pharmacology; D000096983:Ginkgo Extract
chemical_list: D000928:Antidepressive Agents; D046934:Ginkgolides; D010936:Plant Extracts; D000069470:Venlafaxine Hydrochloride; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract
keywords: Antidepressant; Diterpene ginkgolides; Ginkgo biloba extract; Hippocampus; Metabolomics