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

Biomed Pharmacother. 2023 Aug:164:114459. doi: 10.1016/j.biopha.2023.114459. Epub 2023 May 26.

Abstract

Objectives: In this study, we have 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 days. According to the baseline sucrose preference, the male rats were divided into 6 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 of 5-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 p-GSK-3β/GSK-3β of brain tissues were assayed by western blot.

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.

Conclusions: 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.

Keywords: Areca catechu L.; BDNF; CUMS; Depression.

MeSH terms

  • Animals
  • Antidepressive Agents* / pharmacology
  • Areca / metabolism
  • Behavior, Animal
  • Brain-Derived Neurotrophic Factor / metabolism
  • Corticosterone
  • Depression* / drug therapy
  • Depression* / etiology
  • Depression* / metabolism
  • Disease Models, Animal
  • Dopamine / metabolism
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Hippocampus
  • Hypothalamo-Hypophyseal System
  • Male
  • Neurotransmitter Agents / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Pituitary-Adrenal System
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Serotonin / metabolism
  • Signal Transduction
  • Stress, Psychological / complications
  • Stress, Psychological / drug therapy
  • Stress, Psychological / metabolism
  • Sucrose

Substances

  • Antidepressive Agents
  • Brain-Derived Neurotrophic Factor
  • Glycogen Synthase Kinase 3 beta
  • Proto-Oncogene Proteins c-akt
  • Serotonin
  • Corticosterone
  • Dopamine
  • Sucrose
  • Neurotransmitter Agents
  • Phosphatidylinositol 3-Kinases