Areca catechu L. ameliorates chronic unpredictable mil stress-induced depression behavior in rats by the promotion of the BDNF signaling pathway

OBJECTIVE To investigated the anti-depressant effects of the fruit Areca catechu L.(ACL) and elucidated its potential underlying mechanism using a rat model of chronic unpredictable mild stress(CUMS).METHODS CUMS was induced in rats to establish a depression animal model for 28 d. According to the baseline sucrose preference, the male rats were divided into six different groups. They were treated with paroxetine hydrochloride, ACL, and water once a day until the behavioral tests were performed. The levels of corticosterone(CORT), malondialdehyde(MDA), catalase(CAT),and total superoxide dismutase(T-SOD) in serum were detected using a commercial kit, and the concentrations of5-hydroxytryptamine(5-HT) and dopamine(DA) monoamine neurotransmitters in the brain tissues were detected by liquid chromatography-tandem mass spectrometry.Doublecortin(DCX) expression in the hippocampal dentate gyrus(DG) was determined by immunofluorescence,and the relative abundance of brain-derived neurotrophic factor(BDNF), TrkB, PI3K, p-Akt/Akt, PSD-95, and pGSK-3β/GSK-3β of brain tissues were assayed by Western blotting. RESULTS ACL markedly increased sucrose preference, decreased the immobility time, and shortened the feeding latency of CUMS-induced rats. CUMS induction resulted in marked changes in the contents of the monoamine neurotransmitters(5-HT and DA) in the hippocampus and cortex of brain tissues and the levels of CORT, MDA, CAT, and T-SOD in serum, whereas ACL administration alleviated these considerable changes.ACL promoted DCX expression in DG and increased the protein levels of BDNF, TrkB, PI3K, p-Akt/Akt, PSD-95,and p-GSK-3β/GSK-3β in the brains of CUMS-induced rats. CONCLUSION Our results indicated that ACL may improve depression-like behaviors in CUMS-induced rats by decreasing the hyperfunction and oxidative stress of the hypothalamic-pituitary-adrenal axis, stimulating hippocampal neurogenesis, and activating the BDNF signaling pathway.