• Xiangting Li, Ting Wu, Zhonghai Yu, Tingting Li, Jingsi Zhang, Zhennian Zhang, Min Cai, Wen Zhang, Jun Xiang, and Dingfang Cai.
• Department of Integrative Medicine, Zhongshan Hospital, Fudan University, China; Institute of Neurology, Academy of Integrative Medicine, Fudan University, Shanghai 200032, China.
• Biomed. Pharmacother. 2018 Apr 1; 100: 394-406.

BackgroundMajor depressive disorder (MDD) is a common but serious psychiatric disorder, but current treatments are inadequate for approximately half of the patients with MDD. Thus, better methods of treatment are urgently needed. This study aimed to investigate the antidepressant-like effects and potential mechanism of Apocynum venetum leaf extract (AVLE) in chronic unpredictable mild stress (CUMS) rat model of depression.Materials And MethodsThe CUMS rat model of depression was used to investigate the antidepressant-like activity and relevant mechanism of AVLE (30, 60, and 125 mg/kg, i.g.). Behavioral tests, including sucrose preference test (SPT), open field test (OFT), and forced swimming test (FST) were conducted to assess anhedonic, despairing, and spontaneous behaviors, respectively. The activity of the hypothalamic-pituitary-adrenal (HPA) axis was evaluated by measuring the serum adrenocorticotrophic hormone (ACTH) and corticosterone (CORT) concentrations. The underlying mechanism was further explored by assessing oxidative stress parameters, cell apoptosis, and brain-derived neurotrophic factor (BDNF) expression in the rat hippocampus exposed to CUMS.ResultsThe AVLE (36, 60, 125 mg/kg) treatment exerted antidepressant-like effects in CUMS-exposed rats similar to fluoxetine (10 mg/kg). The AVLE treatment reduced the serum CORT and ACTH levels in CUMS rats. It also increased the activities and gene expression of antioxidant enzymes (SOD, CAT, and GPx) and decreased the ROS generation levels and the lipid peroxidation marker MDA in the rat hippocampus subjected to CUMS. Additionally, it suppressed the apoptosis of hippocampus cells by modulating Bcl-2/Bax pathways and improved the hippocampal BDNF expressions of CUMS rats.ConclusionOur findings suggested that AVLE exerted antidepressant-like effects in CUMS rats, which was possibly mediated by the prevention of oxidative stress, the inhibition of hippocampal neuronal apoptosis, and the upregulation of the hippocampal BDNF level.Copyright © 2018 Elsevier Masson SAS. All rights reserved.

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