Antidepressant-like effects of water extract of Gastrodia elata Blume in rats exposed to unpredictable chronic mild stress via modulation of monoamine regulatory pathways

Ethnopharmacology relevance Gastrodia elata Blume (GE) is a traditional herbal medicine belonging to the Orchidaceae family, and has been used to manage neurological disorders for centuries. We have previously reported that its water extract (WGE) could improve the depressive-like behaviours in the forced swimming test (FST), an animal model of depression. Aim of the study To investigate the antidepressant-like effects of WGE in rats exposed to unpredictable chronic mild stress (UCMS) model, and to explore its possible molecular mechanisms. Materials and methods UCMS rats were orally administered with WGE (0.5 g/kg body weight) daily within the 4 weeks UCMS procedure. The sucrose preference test and the open field test were conducted to assess anhedonia and spontaneous behaviours, respectively. The cerebral turnover rates of monoamine neurotransmitters and the serum corticosterone levels were measured. In vitro direct and indirect monoamine oxidase A (MAO-A) inhibitory assays were employed to assess the possible antidepressant-like mechanisms of WGE (0.5 mg/mL) and its major component, gastrodin (GAS, 15, 30 and 60 μg/mL). Western blot was used to examine the expression of protein related to monoamine regulation, such as MAO-A and tyrosine hydroxylase (TH). Results WGE significantly reversed the sucrose preference and other abnormal behaviours induced by 4 weeks of UCMS. WGE significantly restored the cerebral turnover rates of serotonin and dopamine and decreased serum corticosterone levels. WGE and gastrodin inhibited the activity and protein expression of MAO-A, and increased TH levels in PC12 cells. Conclusion The antidepressant-like effects of WGE and gastrodin might be mediated by the regulation of monoamine neurotransmitters, and therefore were beneficial in depression treatment as a complementary approach.