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.