Apocynum venetum Leaf Extract Exerts Antidepressant-Like Effects and Inhibits Hippocampal and Cortical Apoptosis of Rats Exposed to Chronic Unpredictable Mild Stress

Abstract

We investigated the effects of Apocynum venetum leaf extract (AVLE) on depressive behaviors and neuronal apoptosis in a chronic unpredictable mild stress (CUMS) rat model of depression. Rats were randomly divided into six groups: control, chronic unpredictable mild stress, fluoxetine, AVLE30, AVLE60, and AVLE120. Except for the control group, all rats were submitted to chronic unpredictable mild stress paradigms for four weeks to induce depressive behavior. Neuronal apoptosis was assessed by the terminal deoxynucleotidyl transferase- (TDT-) mediated dUTP-biotin nick end-labeling (TUNEL) method. The expression levels of apoptosis-related proteins, such as B-cell lymphoma 2 (Bcl-2), Bcl-2 Associated X Protein (Bax), cysteine-aspartic acid protease-3 and protease-9 (caspase-3 and caspase-9), cytochrome c (cyt-C), brain-derived neurotrophic factor (BDNF), and cAMP-response element binding (CREB) protein, were evaluated by western blot. Treatment with AVLE (60 or 120 mg/kg/day) significantly improved depressive behavior. Increased apoptosis of hippocampus and cortical neurons were observed in CUMS rats, while 120 mg/kg/day of AVLE significantly reversed these changes and achieved the best antidepressant-like effects among the doses tested. Moreover, AVLE (120 mg/kg) significantly increased Bcl-2, BDNF, and CREB protein expression and decreased Bax, cyt-C, and caspase family protein expression. Our results indicate that AVLE has potent antidepressant activity, likely due to its ability to suppress neuronal apoptosis.