Anti-depressive-like and cognitive impairment alleviation effects of Gastrodia elata Blume water extract is related to gut microbiome remodeling in ApoE -/- mice exposed to unpredictable chronic mild stress.

Ethnopharmacology Relevance: Gastrodia elata Blume (GE) is a traditional Chinese dietary therapy used to treat neurological disorders. Gastrodia elata Blume water extract (WGE) has been shown to ameliorate inflammation and improve social frustration in mice in a chronic social defeat model. However, studies on the anti-depressive-like effects and cognitive impairment alleviation related to the impact of WGE on the gut microbiome of ApoE ^-/- mice remain elusive.
Aim of the Study: The present study aimed to investigate the anti-depressive-like effect and cognitive impairment alleviation and mechanisms of WGE in ApoE ^-/- mice subjected to unpredictable chronic mild stress (UCMS), as well as its impact on the gut microbiome of the mice.
Materials and Methods: Sixty ApoE ^-/- mice (6 months old) were randomly grouped into six groups: control, UCMS, WGE groups [5, 10, 20 mL WGE/kg body weight (bw) + UCMS], and a positive group (fluoxetine 20 mg/kg bw + UCMS). After four weeks of the UCMS paradigm, the sucrose preference, novel object recognition, and open field tests were conducted. The neurotransmitters serotonin (5-HT), dopamine (DA) and their metabolites were measured in the prefrontal cortex. Serum was collected to measure corticosterone and amyloid-42 (Aβ-42) levels. Feces were collected, and the gut microbiome was analyzed.
Results: WGE restored sucrose preference, exploratory behavior, recognition ability, and decreased the levels of serum corticosterone and Aβ-42 in ApoE ^-/- mice to alleviate depressive-like behavior and cognitive impairment. Furthermore, WGE regulated the monoamine neurotransmitter via reduced the 5-HT and DA turnover rates in the prefrontal cortex. Moreover, WGE elevated the levels of potentially beneficial bacteria such as Bifidobacterium, Akkermansia, Alloprevotella, Defluviitaleaceae_UCG-011, and Bifidobacterium pseudolongum as well as balanced fecal short-chain fatty acids (SCFAs).
Conclusion: WGE demonstrates anti-depressive-like effects, cognitive impairment alleviation, and gut microbiome and metabolite regulation in ApoE ^-/- mice. Our results support the possibility of developing a functional and complementary medicine to prevent or alleviate depression and cognitive decline using WGE in CVDs patients.
Competing Interests: Declaration of competing interest The authors declare no conflicts of interest.
(Copyright © 2022. Published by Elsevier B.V.)