PMID- 31278631 OWN - NLM STAT- MEDLINE DCOM- 20200120 LR - 20211204 IS - 1573-6903 (Electronic) IS - 0364-3190 (Linking) VI - 44 IP - 9 DP - 2019 Sep TI - Licorisoflavan A Exerts Antidepressant-Like Effect in Mice: Involvement of BDNF-TrkB Pathway and AMPA Receptors. PG - 2044-2056 LID - 10.1007/s11064-019-02840-2 [doi] AB - Depression is a highly debilitating and life-threatening psychiatric disorder. The classical antidepressants are still not adequate due to undesirable side effects. Therefore, the development of new drugs for depression treatment is an urgent strategic to achieving clinical needs. Licorisoflavan A is a bioactive ingredient isolated from Glycyrrhizae Radix and has been recently reported for neuroprotective effects. In this study, the antidepressant-like effect and neural mechanism of licorisoflavan A were explored. In the mice behavioral despair test, we observed that licorisoflavan A exhibited powerful antidepressant-like effect in forced swimming test (FST), tail suspension test (TST), without affecting locomotor activity in open field test (OFT). Additionally, licorisoflavan A administration significantly restored Chronic mild stress (CMS)-induced changes in sucrose preference test (SPT), FST, and TST, without altering the locomotion in OFT. In chronical-stimulated mice, the licorisoflavan A treatment effectively attenuated the expressions of Brain-derived neurotrophic factor (BDNF), tyrosine kinase B (TrkB), the phosphorylations of cAMP response element binding protein (CREB), extracellular signal-regulated kinase (ERK)-1/2, eukaryotic elongation factor 2 (eEF2), mammalian target of rapamycin (mTOR), initiation factor 4E-binding protein 1 (4E-BP-1), and p70 ribosomal protein S6 kinase (p70S6K) in hippocampus of CMS-induced mice. Additionally, licorisoflavan A could reverse the decreases in synaptic proteins post-synaptic density protein 95 (PSD-95) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor subunit glutamate receptor 1 (GluR1) caused by CMS, and its antidepressant-like effect was blocked by the AMPA receptor antagonist NBQX. These findings served as preclinical evidence that licorisoflavan A exerted potent antidepressant-like effects involving BDNF-TrkB pathway and AMPA receptors. Licorisoflavan A might be used as a potential medicine against depression-like disorder. FAU - Xiao, Dong AU - Xiao D AD - College of Pharmacy, Guangdong Medical University, Dongguan, 523808, China. FAU - Liu, Li AU - Liu L AD - College of Pharmacy, Guangdong Medical University, Dongguan, 523808, China. liuli-44@163.com. FAU - Li, Yuanjie AU - Li Y AD - College of Pharmacy, Ningxia Medical University, Ningxia, 750004, China. FAU - Ruan, Jie AU - Ruan J AD - College of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing, 210009, China. FAU - Wang, Hanqing AU - Wang H AD - College of Pharmacy, Ningxia Medical University, Ningxia, 750004, China. hqwangnx@tom.com. AD - Ningxia Research Center of Modern Hui Medicine Engineering and Technology, Ningxia Medical University, Yinchuan, 750004, China. hqwangnx@tom.com. LA - eng GR - 81873096/National Natural Science Foundation of China/ GR - 81603227/National Natural Science Foundation of China/ GR - 81503465/National Natural Science Foundation of China/ GR - 81460645/National Natural Science Foundation of China/ PT - Journal Article DEP - 20190705 PL - United States TA - Neurochem Res JT - Neurochemical research JID - 7613461 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Antidepressive Agents) RN - 0 (Bdnf protein, mouse) RN - 0 (Benzopyrans) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cell Cycle Proteins) RN - 0 (Creb1 protein, mouse) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (Eif4ebp1 protein, mouse) RN - 0 (Membrane Glycoproteins) RN - 0 (Receptors, AMPA) RN - 0 (licorisoflavan A) RN - EC 2.7.10.1 (Ntrk2 protein, mouse) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) SB - IM MH - Adaptor Proteins, Signal Transducing/metabolism MH - Animals MH - Antidepressive Agents/isolation & purification/*therapeutic use MH - Behavior, Animal/drug effects MH - Benzopyrans/isolation & purification/*therapeutic use MH - Brain-Derived Neurotrophic Factor/metabolism MH - Cell Cycle Proteins/metabolism MH - Cyclic AMP Response Element-Binding Protein/metabolism MH - Depression/*drug therapy MH - Hippocampus/metabolism MH - Locomotion/drug effects MH - Male MH - Membrane Glycoproteins/metabolism MH - Mice MH - Phosphorylation/drug effects MH - Protein Serine-Threonine Kinases/metabolism MH - Protein-Tyrosine Kinases/metabolism MH - Receptors, AMPA/*metabolism MH - Signal Transduction/*drug effects OTO - NOTNLM OT - AMPA OT - Antidepressant-like effect OT - BDNF-TrkB signaling pathway OT - Chronic mild stress OT - Licorisoflavan A EDAT- 2019/07/07 06:00 MHDA- 2020/01/21 06:00 CRDT- 2019/07/07 06:00 PHST- 2019/02/26 00:00 [received] PHST- 2019/06/30 00:00 [accepted] PHST- 2019/06/23 00:00 [revised] PHST- 2019/07/07 06:00 [pubmed] PHST- 2020/01/21 06:00 [medline] PHST- 2019/07/07 06:00 [entrez] AID - 10.1007/s11064-019-02840-2 [pii] AID - 10.1007/s11064-019-02840-2 [doi] PST - ppublish SO - Neurochem Res. 2019 Sep;44(9):2044-2056. doi: 10.1007/s11064-019-02840-2. Epub 2019 Jul 5.