Drug Design, Development and Therapy (Mar 2020)

Diterpene Ginkgolides Exert an Antidepressant Effect Through the NT3-TrkA and Ras-MAPK Pathways

  • Wang T,
  • Bai S,
  • Wang W,
  • Chen Z,
  • Chen J,
  • Liang Z,
  • Qi X,
  • Shen H,
  • Xie P

Journal volume & issue
Vol. Volume 14
pp. 1279 – 1294

Abstract

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Ting Wang,1– 3,* Shunjie Bai,1– 3,* Wei Wang,2– 4,* Zhi Chen,2,3 Jianjun Chen,2,3 Zihong Liang,5 Xunzhong Qi,2– 4 Hailan Shen,1 Peng Xie1– 6 1Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Chongqing Key Laboratory of Neurobiology, Chongqing, People’s Republic of China; 4Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 5Department of Neurology, The Inner Mongolia Autonomous Region People’s Hospital, Hohhot, Inner Mongolia, People’s Republic of China; 6Chongqing Key Laboratory of Cerebrovascular Disease Research, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Peng XieDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaTel +86-23-68485490Fax +86-23-68485111Email [email protected]: Depression is a highly prevalent mental illness that severely impacts the quality of life of affected individuals. Our recent studies demonstrated that diterpene ginkgolides (DG) have antidepressant effects in mice. However, the underlying molecular mechanisms remained much unclear.Methods: In this study, we assessed the antidepressant effects of chronic DG therapy in rats by evaluating depression-related behaviors, we also examined potential side effects using biochemical indicators. Furthermore, we performed an in-depth molecular network analysis of gene–protein–metabolite interactions on the basis of metabolomics.Results: Chronic DG treatment significantly ameliorated the depressive-like behavioral phenotype. Furthermore, the neurotrophin signaling-related NT3-TrkA and Ras-MAPK pathways may play an important role in the antidepressant effect of DG in the hippocampus.Conclusion: These findings provide novel insight into the mechanisms underlying the antidepressant action of DG, and should help advance the development of new therapeutic strategies for depression.Keywords: diterpene ginkgolides, antidepressant, neurotrophin, hippocampus, NT3-TrkA and Ras-MAPK pathways

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