Antidepressant-like effects of Xiaochaihutang in a rat model of chronic unpredictable mild stress

Abstract

Ethnopharmacological relevance: Xiaochaihutang (XCHT) has been used in China for thousands of years to treat "Shaoyang syndrome", which involves depressive-like symptoms. However, few studies have investigated its antidepressant effects and pharmacological mechanism of action. The present study was designed to confirm the antidepressant effect of XCHT using a chronic unpredictable mild stress (CUMS) model and explore its potential mechanism of action by investigating the monoamine neurotransmitters (dopamine and 5-hydroxytryptamine) and neurotrophins (BDNF and NGF).

Materials and methods: The CUMS model was established in rats, and the antidepressant effect of XCHT (0.6, 1.7 and 5mg/kg/day, given by gastric gavage for 4 weeks) was investigated using the open field test (OFT), food consumption test and sucrose preference test. The concentrations of 5-HT and DA in the hippocampus were measured by high performance liquid chromatography with electrochemical detection (HPLC-ECD). The expressions of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and their receptors tyrosine receptor kinase B (TrkB) and tyrosine receptor kinase A (TrkA) in the hippocampus were measured by immunohistochemical staining analysis.

Results: CUMS caused a significant decrease in OFT, food consumption and sucrose preference in rats, and these depression-like behaviors were significantly improved by XCHT (1.7 and 5 g/kg/day). Moreover, XCHT significantly increased the concentrations of 5-HT (0.6 and 5 g/kg/day) and DA (5 g/kg/day), and improved the BDNF, NGF, TrkB and TrkA expressions in the hippocampus (1.7 and 5 g/kg/day), which was reduced in CUMS rats.

Conclusion: The results obtained suggested that XCHT may have therapeutic actions on depression-like behavior induced by CUMS in rats possibly mediated by increasing the monoamine neurotransmitter concentration and neurotrophin expression in the hippocampus.

Keywords: 5-Hydroxytryptamine (PubChem CID: 5202); Antidepressant; Baicalein (PubChem CID: 5281605); Baicalin (PubChem CID: 64982); CUMS; Dopamine (PubChem CID: 681); Ginsenoside Rg(1) (PubChem CID: 441923); Glycyrrhizic acid (PubChem CID: 14982); Isoliquiritin (PubChem CID: 5318591); Liquiritin (PubChem CID: 503737); Monoamine; Neurotrophin; Saikosaponin A (PubChem CID: 167928); Wogonin (PubChem CID: 5281703); Xiaochaihutang.