PMID- 29680784 OWN - NLM STAT- MEDLINE DCOM- 20181105 LR - 20181202 IS - 1872-7549 (Electronic) IS - 0166-4328 (Linking) VI - 348 DP - 2018 Aug 1 TI - Silibinin exerts antidepressant effects by improving neurogenesis through BDNF/TrkB pathway. PG - 184-191 LID - S0166-4328(18)30157-8 [pii] LID - 10.1016/j.bbr.2018.04.025 [doi] AB - Classic antidepressants benefit depression patients partially by improving neurogenesis and/or brain-derived neurotrophic factor (BDNF)/TrkB pathway which were impaired in depression. In this study, we demonstrated that Silibinin (SLB), a polyphenolic flavanoid from Silybum marianum, ameliorated reserpinized mouse depressant-like behaviors. The antidepressants of SLB administration was associated with increased neural stem cells (NSCs) proliferation and further confirmed in BDNF/TrkB signaling transduction. SLB treatment reversed the decreased expression levels of BDNF and its receptor TrkB, and the reduced activation of downstream target proteins including phosphorylated extracellular-regulated protein kinase (p-ERK) and phosphorylated cAMP-response element binding protein (p-CREB) in depressived hippocampus. Furthermore, intracerebroventricular injection of GNF5837, a TrkB antagonist, abrogated antidepressant-like effects of SLB in mice along with the improved NSC proliferation, as well as enhanced levels of p-ERK and p-CREB in mice hippocampus. Taken together, these results suggest that SLB may exert antidepressant effects through BDNF/TrkB signaling pathway to improve NSC proliferation in acute depression. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Li, Yan-Jiao AU - Li YJ AD - Precision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, 710038, PR China; Department of Pharmacology, School of Pharmacy, the Fourth Military Medical University, Xi'an, Shaanxi Province, 710032, PR China; Department of Acupuncture-moxibustion-massage, Shaanxi University of Chinese Medicine, Xi'an, Shaanxi Province, 712000, PR China. FAU - Li, Yu-Jiao AU - Li YJ AD - Department of Pharmacology, School of Pharmacy, the Fourth Military Medical University, Xi'an, Shaanxi Province, 710032, PR China. FAU - Yang, Liu-Di AU - Yang LD AD - Department of Pharmacology, School of Pharmacy, the Fourth Military Medical University, Xi'an, Shaanxi Province, 710032, PR China; Department of Acupuncture-moxibustion-massage, Shaanxi University of Chinese Medicine, Xi'an, Shaanxi Province, 712000, PR China. FAU - Zhang, Kun AU - Zhang K AD - Department of Pharmacology, School of Pharmacy, the Fourth Military Medical University, Xi'an, Shaanxi Province, 710032, PR China. FAU - Zheng, Kai-Yin AU - Zheng KY AD - Precision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, 710038, PR China; Department of Pharmacology, School of Pharmacy, the Fourth Military Medical University, Xi'an, Shaanxi Province, 710032, PR China. FAU - Wei, Xin-Miao AU - Wei XM AD - Student Brigade, the Fourth Military Medical University, Xi'an, Shaanxi Province, 710032, PR China. FAU - Yang, Qi AU - Yang Q AD - Department of Pharmacology, School of Pharmacy, the Fourth Military Medical University, Xi'an, Shaanxi Province, 710032, PR China. FAU - Niu, Wen-Min AU - Niu WM AD - Department of Acupuncture-moxibustion-massage, Shaanxi University of Chinese Medicine, Xi'an, Shaanxi Province, 712000, PR China. FAU - Zhao, Ming-Gao AU - Zhao MG AD - Precision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, 710038, PR China; Department of Pharmacology, School of Pharmacy, the Fourth Military Medical University, Xi'an, Shaanxi Province, 710032, PR China. FAU - Wu, Yu-Mei AU - Wu YM AD - Precision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, 710038, PR China; Department of Pharmacology, School of Pharmacy, the Fourth Military Medical University, Xi'an, Shaanxi Province, 710032, PR China; Department of Acupuncture-moxibustion-massage, Shaanxi University of Chinese Medicine, Xi'an, Shaanxi Province, 712000, PR China. Electronic address: yumeiwu@fmmu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180420 PL - Netherlands TA - Behav Brain Res JT - Behavioural brain research JID - 8004872 RN - 0 (Antidepressive Agents) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Membrane Glycoproteins) RN - 0 (Silymarin) RN - 4RKY41TBTF (Silybin) RN - EC 2.7.10.1 (Ntrk2 protein, mouse) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) SB - IM MH - Animals MH - Antidepressive Agents MH - Brain-Derived Neurotrophic Factor/metabolism MH - Depression/metabolism MH - Depressive Disorder/drug therapy MH - Disease Models, Animal MH - Male MH - Membrane Glycoproteins/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Neural Stem Cells/drug effects MH - Neurogenesis/drug effects MH - Phosphorylation/drug effects MH - Protein-Tyrosine Kinases/metabolism MH - Signal Transduction/drug effects MH - Silybin MH - Silymarin/*metabolism/*pharmacology MH - Stress, Psychological/metabolism OTO - NOTNLM OT - Acute depression OT - Brain-derived neurotrophic factor OT - Neural stem cell OT - Neurogenesis OT - Silibinin OT - TrkB EDAT- 2018/04/24 06:00 MHDA- 2018/11/06 06:00 CRDT- 2018/04/23 06:00 PHST- 2018/01/30 00:00 [received] PHST- 2018/03/20 00:00 [revised] PHST- 2018/04/17 00:00 [accepted] PHST- 2018/04/24 06:00 [pubmed] PHST- 2018/11/06 06:00 [medline] PHST- 2018/04/23 06:00 [entrez] AID - S0166-4328(18)30157-8 [pii] AID - 10.1016/j.bbr.2018.04.025 [doi] PST - ppublish SO - Behav Brain Res. 2018 Aug 1;348:184-191. doi: 10.1016/j.bbr.2018.04.025. Epub 2018 Apr 20.