Tao-Hong-Si-Wu decoction improves depressive symptoms in model rats via amelioration of BDNF-CREB-arginase I axis disorders

Abstract

Context: The traditional Chinese medicine formula Tao-Hong-Si-Wu decoction (TSD), used for treating ischaemic stroke, has the potential to treat depressive disorder (DD). Objective: To explore the effective targets of TSD on DD animal models. Materials and methods: Sprague-Dawley (SD) rats were modelled by inducing chronic unpredictable mild stress (CUMS) during 35 days and treated with three dosages of TSD (2.5, 5 and 10 g/kg) or fluoxetine (10 mg/kg) by oral gavage for 14 days. Bodyweight measurements and behavioural tests were performed to observe the effect of TSD on the CUMS animals. A gas chromatography coupled with mass spectrometry (GC–MS)-based metabolomic analysis was conducted to reveal the metabolic characteristics related to the curative effect of TSD. Levels of the proteins associated with the feature metabolites were analysed. Results: Reduced immobile duration and crossed squares in the behavioural tests were raised by 48.6% and 32.9%, on average, respectively, by TSD treatment (ED50=3.2 g/kg). Antidepressant effects of TSD were associated with 13 decreased metabolites and the restorations of ornithine and urea in the serum. TSD (5 g/kg) raised serum serotonin by 54.1 mg/dL but suppressed arginase I (Arg I) by 47.8 mg/dL in the CUMS rats. Proteins on the brain-derived neurotrophic factor (BDNF)-cAMP response element-binding protein (CREB) axis that modulate the inhibition of Arg I were suppressed in the CUMS rats but reversed by the TSD intervention. Discussion and conclusions: TSD improves depression-like symptoms in CUMS rats. Further study will focus on the antidepressant-like effects of effective compounds contained in TSD.